An In-Depth Analysis of 1,2-Distearoylphosphatidylcholine (DSPC): From Physicochemical Properties to Advanced Pharmaceutical Applications

Executive Summary

1,2-Distearoylphosphatidylcholine (DSPC) is a fully saturated, synthetic phospholipid that has emerged as an indispensable excipient in the field of advanced drug delivery. While its primary role is to serve as a structural component in lipid-based nanocarriers, such as liposomes and lipid nanoparticles (LNPs), its function extends far beyond that of an inert scaffold. This report provides a comprehensive analysis of DSPC, synthesizing data on its chemical identity, physicochemical characteristics, pharmacological activity, and regulatory standing to present a holistic view of its significance in modern medicine.

The defining feature of DSPC is its high main phase transition temperature () of approximately 55°C. This property ensures that at physiological temperature (37°C), DSPC-based lipid bilayers exist in a highly ordered, rigid "gel" phase. This physical state confers exceptional structural stability and low permeability to drug delivery systems, minimizing premature drug leakage and extending the shelf-life of pharmaceutical products. These characteristics have made DSPC a cornerstone lipid in formulations requiring long systemic circulation times and controlled release kinetics. Its utility is exemplified by its inclusion in several clinically approved products, most notably as a critical structural component in the LNP formulations for the Pfizer-BioNTech and Moderna COVID-19 mRNA vaccines, where it provides the necessary stability to protect the fragile mRNA payload.

Furthermore, recent research has unveiled that DSPC is not merely a passive structural element but an active participant in modulating biological responses. When formulated into liposomes for vaccine delivery, DSPC exhibits potent adjuvant properties. Its gel-phase structure enhances antigen presentation by dendritic cells, upregulates crucial costimulatory molecules, and stimulates the release of pro-inflammatory cytokines, thereby augmenting the overall immune response to the vaccine antigen.

Pharmacokinetically, the incorporation of DSPC into nanocarriers dramatically prolongs their circulation half-life, transforming the disposition profile of the encapsulated drug. This is achieved by creating a stable, rigid particle that evades rapid clearance by the mononuclear phagocyte system. The compound possesses an excellent safety profile, is considered Generally Recognized as Safe (GRAS) for certain applications, and is well-established with global regulatory agencies, including the U.S. Food and Drug Administration (FDA). This combination of superior physicochemical stability, immunomodulatory activity, favorable pharmacokinetics, and a strong safety record positions DSPC as a pivotal enabling technology for a wide array of advanced therapeutics, from chemotherapy and medical imaging to the rapidly expanding field of nucleic acid-based medicines.

Compound Identification and Chemical Profile

A precise and unambiguous identification of a pharmaceutical excipient is fundamental to its successful application in research, development, and commercial manufacturing. 1,2-Distearoyllecithin, commonly known by the acronym DSPC, is a well-defined small molecule with a complex nomenclature that reflects its chemical structure and stereochemistry. This section provides a definitive profile of the compound, collating its various names, registry identifiers, and structural details.

Nomenclature and Synonyms

The compound is known by a multitude of names across scientific literature, commercial catalogs, and regulatory databases. Establishing a clear understanding of this synonymy is crucial for accurate information retrieval and communication. The primary names include 1,2-Distearoyllecithin, 1,2-Distearoylphosphatidylcholine, and the widely used abbreviation, Distearoylphosphatidylcholine (DSPC).[1]

Systematic nomenclature according to the International Union of Pure and Applied Chemistry (IUPAC) provides a more descriptive chemical identity. For the racemic mixture, the name is 2,3-di(octadecanoyloxy)propyl 2-(trimethylazaniumyl)ethyl phosphate.[4] However, in biological systems and many high-purity pharmaceutical preparations, the specific stereoisomer is used, which has the systematic IUPAC name (2R)-2,3-Bis(octadecanoyloxy)propyl 2-(trimethylazaniumyl)ethyl phosphate.[2] This R-configuration corresponds to the naturally occurring L-α or

sn-glycero-3 configuration of phospholipids.

Other common synonyms and shorthand notations found in literature include:

• Dioctadecanoyl phosphatidylcholine [1]
• Dioctadecanoyllecithin [1]
• L-α-Phosphatidylcholine, distearoyl [6]
• L-β,γ-Distearoyl-α-lecithin [6]
• PC(18:0/18:0), a lipidomics notation indicating a phosphatidylcholine with two 18-carbon saturated (0 double bonds) acyl chains [6]
• Coatsome MC 8080 [7]

Chemical and Registry Identifiers

To ensure unequivocal identification, a comprehensive list of registry numbers from various global databases is essential. A critical distinction exists between the racemic form and the enantiomerically pure form, which are assigned different CAS numbers. This distinction, while subtle, has significant implications for manufacturing, quality control, and regulatory filings, where precise chemical identity is mandatory. The use of a racemic mixture versus a pure enantiomer dictates raw material sourcing, characterization methods, and the information presented in regulatory dossiers. While the bulk physicochemical properties are nearly identical, the stereochemical purity is a critical quality attribute for advanced pharmaceutical products.

The primary identifiers for the racemic (DL-) form, which corresponds to the DrugBank ID DB14099, are:

• DrugBank Accession Number: DB14099 [1]
• CAS Number: 4539-70-2 [1]
• UNII: EAG959U971 [1]
• PubChem CID: 65146 [4]
• RxCUI: 1426932 [4]

The primary identifiers for the R-enantiomer (L-α or sn-glycero-3 form), which is commonly used in pharmaceutical formulations, are:

• CAS Number: 816-94-4 [2]
• UNII: 043IPI2M0K [2]
• PubChem CID: 94190 [2]
• ChEBI ID: CHEBI:83718 [2]
• EC Number: 212-440-2 [2]

A consolidated list of these identifiers is presented in Table 1 for ease of reference.

Table 1: Compound Identification and Synonyms

Identifier Type	Racemic (DL-) Form	R-Enantiomer (L-α, sn-glycero-3) Form
Primary Name	1,2-Distearoyl-DL-phosphatidylcholine	1,2-Distearoyl-sn-glycero-3-phosphocholine
Common Name	1,2-Distearoyllecithin	1,2-Distearoyllecithin
DrugBank ID	DB14099	Not explicitly assigned, but related
CAS Number	4539-70-2	816-94-4
UNII	EAG959U971	043IPI2M0K
PubChem CID	65146	94190
RxCUI	1426932	1426933
EC Number	306-549-5 (from PubChem)	212-440-2
InChIKey	NRJAVPSFFCBXDT-UHFFFAOYSA-N	NRJAVPSFFCBXDT-HUESYALOSA-N

Molecular Structure and Stereochemistry

DSPC is a glycerophospholipid, a class of lipids that form the primary structural basis of biological membranes.[1] Its molecular structure consists of a glycerol backbone, two stearic acid chains attached at the

sn-1 and sn-2 positions via ester linkages, and a phosphocholine head group attached at the sn-3 position.[11]

• Molecular Formula:  [2]
• Molecular Weight (Average): Approximately 790.15 g/mol to 790.161 g/mol depending on the source.[2]
• Monoisotopic Mass: 789.624755 Da.[1]

The structural representations provide a precise map of the molecule's connectivity and, where applicable, stereochemistry.

• InChI (Racemic): InChI=1S/C44H88NO8P/c1-6-8-10-12-14-16-18-20-22-24-26-28-30-32-34-36-43(46)50-40-42(41-52-54(48,49)51-39-38-45(3,4)5)53-44(47)37-35-33-31-29-27-25-23-21-19-17-15-13-11-9-7-2/h42H,6-41H2,1-5H3 [1]
• InChIKey (Racemic): NRJAVPSFFCBXDT-UHFFFAOYSA-N [1]
• SMILES (Racemic): CCCCCCCCCCCCCCCC(=O)OCC(COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCC [1]
• SMILES (R-Enantiomer): CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(=O)([O-])OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCC [5]

The key difference in the SMILES string for the R-enantiomer is the [C@H] notation, which specifies the stereochemistry at the chiral center of the glycerol backbone (the sn-2 position). This structural precision is vital for defining materials used in GMP manufacturing. Chemically, DSPC belongs to the class of phosphatidylcholines, which are zwitterionic at physiological pH due to the negatively charged phosphate group and the positively charged quaternary ammonium group of the choline head.[1]

Physicochemical Properties and Their Pharmaceutical Relevance

The utility of DSPC as a pharmaceutical excipient is a direct consequence of its distinct physicochemical properties. These characteristics govern its behavior in aqueous environments, its interaction with other molecules, and the ultimate performance of the drug delivery systems it helps to form. Understanding the link between these properties and their functional implications is essential for rational formulation design.

Key Physical and Chemical Parameters

DSPC is typically supplied as a white crystalline powder or solid.[3] Its molecular structure, featuring two long, saturated hydrocarbon tails and a polar head group, defines its physical behavior.

• Phase Transition Temperature (): The most critical property of DSPC is its high main phase transition temperature (), which is the temperature at which the lipid bilayer transitions from an ordered gel phase to a disordered liquid-crystalline phase. For DSPC, this temperature is consistently reported to be approximately 55°C, with values ranging from 54°C to 55.6°C depending on the measurement technique and sample conditions.[7] The minor variations in these reported values are not indicative of error but rather highlight the sensitivity of the phase transition to factors such as hydration, purity, and the presence of other molecules like cholesterol. In a practical formulation, the overall phase behavior is a complex function of all components, not just the  of pure DSPC. Nevertheless, the high  ensures that at physiological temperature (37°C), DSPC membranes are well below their transition point and exist in a rigid, tightly packed gel state.[23]
• Solubility: DSPC exhibits classic amphiphilic solubility. It is virtually insoluble in water, with a calculated water solubility of approximately  mg/mL.[1] Conversely, it is soluble in various organic solvents. Reports indicate solubility in ethanol at concentrations from approximately 1 mg/mL to 25 mg/mL (often requiring warming and sonication) and in solvent mixtures like chloroform:methanol:water (e.g., at 5 mg/mL in a 65:25:4 ratio).[7] This differential solubility is the driving force behind its self-assembly into bilayer structures when an organic solution of the lipid is introduced into an aqueous phase.
• Lipophilicity and Charge: The molecule is highly lipophilic, as indicated by its high calculated partition coefficient () value of 9.89.[1] The phosphocholine head group contains both a negatively charged phosphate group (strongest acidic  of 1.86) and a permanently positively charged quaternary amine (strongest basic  of -6.7). This makes the molecule zwitterionic, with a net physiological charge of 0.[1]
• Molecular Descriptors: Other computed properties provide further detail on its molecular characteristics. It has a polar surface area of 111.19 , 4 hydrogen bond acceptors, and 0 hydrogen bond donors. The long acyl chains contribute to a high rotatable bond count of 44, providing conformational flexibility to the tails, which becomes particularly relevant above the .[1]

The Critical Role of High Phase Transition Temperature

The high  of DSPC is the cornerstone of its utility in drug delivery. This single parameter is directly responsible for several key performance attributes of DSPC-containing nanoparticles.

1. Membrane Rigidity and Stability: Because physiological temperature is significantly below the , DSPC molecules in a bilayer are arranged in a highly ordered, tightly packed lattice known as the gel phase. This rigidity imparts exceptional mechanical stability to liposomes and LNPs, protecting them from premature dissociation in the bloodstream and contributing to a long shelf-life.[27] Comparative studies have shown that liposomes formulated with DSPC are more stable than those made with lipids having a lower , such as 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC; ).[29]
2. Low Permeability and Enhanced Drug Retention: The tight packing of the acyl chains in the gel phase creates a highly impermeable barrier. This is crucial for minimizing the premature leakage of encapsulated drugs from the nanocarrier's core, a common failure point for liposomes made from more fluid lipids.[19] This high retention capacity ensures that the drug remains within the carrier until it reaches its target site, maximizing therapeutic efficacy and minimizing off-target side effects.

Amphiphilicity and Self-Assembly

DSPC's molecular architecture, comprising a hydrophilic phosphocholine head and two hydrophobic stearoyl tails, defines it as an amphiphile.[3] When dispersed in an aqueous medium, these molecules spontaneously arrange themselves to minimize the unfavorable contact between the hydrophobic tails and water. The cylindrical shape of the DSPC molecule, where the cross-sectional area of the head group is similar to that of the two tails, favors the formation of planar bilayer sheets (lamellar phases).[21] These bilayers then close upon themselves to form spherical vesicles known as liposomes, which can encapsulate an aqueous volume.[31]

The stability of these lamellar phases can be further enhanced by the inclusion of other lipids, most notably cholesterol. Cholesterol inserts itself between the phospholipid molecules, modulating membrane fluidity and packing. In DSPC-based systems, cholesterol helps to stabilize the gel-phase bilayer and can prevent the formation of undesirable, unstable structures, such as interdigitated phases, which can occur under certain conditions (e.g., in the presence of co-solvents like propylene glycol at elevated temperatures).[31] This synergistic interaction between DSPC and cholesterol is a foundational principle in the design of robust liposomal drug delivery vehicles.

Table 2: Summary of Key Physicochemical Properties and their Pharmaceutical Implications

Property	Value	Pharmaceutical Implication
Phase Transition Temp. ()	~55°C	Ensures the lipid bilayer is in a rigid, ordered gel phase at body temperature (37°C). This leads to high structural stability and low membrane permeability, enhancing drug retention and in vivo circulation time.
Water Solubility	~ mg/mL	Extremely low water solubility drives the self-assembly of DSPC into bilayer vesicles (liposomes) in aqueous media, enabling the encapsulation of therapeutic agents.
Organic Solvent Solubility	Soluble in ethanol, chloroform/methanol	Allows for the initial dissolution of the lipid during manufacturing processes (e.g., solvent injection, thin-film hydration) before introduction to an aqueous phase.
Physiological Charge	Zwitterionic (Net Neutral)	Results in liposomes with a neutral surface charge, which can help reduce non-specific interactions with plasma proteins and cells, contributing to longer circulation times.
Molecular Geometry	Cylindrical	Favors the formation of stable, planar bilayers (lamellar phases), which are the fundamental structural units of liposomes used in drug delivery.

Role as a Key Excipient in Advanced Drug Delivery Systems

Leveraging its unique physicochemical properties, DSPC has become a cornerstone excipient in the formulation of sophisticated drug delivery systems. Its primary function is to serve as the principal structural component, or "backbone," of lipid-based nanoparticles, providing the stability and integrity necessary for therapeutic efficacy.

Liposomes and Lipid Nanoparticles (LNPs): The Structural Backbone

DSPC is a fundamental building block for the lipid bilayer that constitutes the shell of both liposomes and lipid nanoparticles (LNPs).[3] In these systems, it is often referred to as a "helper lipid" or "structural lipid," distinguishing it from other components that may have different functions, such as PEGylated lipids that provide stealth properties or cationic lipids that bind nucleic acids.[2] The two long, saturated stearoyl chains of DSPC create a thick, rigid, and well-ordered bilayer, which is essential for maintaining the particle's structure during storage and after administration into the complex biological environment of the bloodstream.[27]

Impact on Formulation Stability and Drug Encapsulation

The choice of DSPC as the primary structural lipid has profound effects on the critical quality attributes of a nanomedicine formulation.

• Physical Stability: The high phase transition temperature of DSPC ensures that the resulting nanoparticles are exceptionally stable. Liposomes formulated with DSPC as the major component demonstrate greater stability compared to those made with lipids possessing lower transition temperatures, such as DPPC.[29] This enhanced stability prevents aggregation and fusion of nanoparticles and minimizes the premature leakage of the encapsulated drug, contributing to a longer product shelf-life and more predictable in vivo performance.
• Drug Encapsulation: The amphiphilic nature of DSPC allows for the versatile encapsulation of a wide range of therapeutic agents. Hydrophilic drugs can be loaded into the aqueous core of the liposome, while lipophilic (hydrophobic) drugs can be partitioned within the lipid bilayer itself.[32] The rigid nature of the DSPC bilayer is particularly advantageous for retaining small, water-soluble molecules that might otherwise readily leak from more fluid membranes.
• Role of Cholesterol: In many formulations, DSPC is combined with cholesterol. This combination is highly synergistic; cholesterol inserts into the DSPC bilayer, further reducing its permeability and enhancing the stability of the lamellar phase, making the resulting vesicles even more robust and suitable as drug delivery vehicles.[31]

Case Study: mRNA Vaccines (Moderna and Pfizer-BioNTech)

The most prominent and impactful application of DSPC in recent years has been its role in the COVID-19 mRNA vaccines developed by Moderna (mRNA-1273) and Pfizer-BioNTech (BNT162b2).[2] The success of these vaccines was critically dependent on the lipid nanoparticle technology used to deliver the fragile mRNA payload to host cells.

In these LNP formulations, DSPC serves as one of four essential lipid components:

1. Ionizable Cationic Lipid: Binds and compacts the negatively charged mRNA.
2. PEGylated Lipid: Forms a hydrophilic shell on the LNP surface to prevent opsonization and clearance by the immune system, prolonging circulation time.
3. Cholesterol: A membrane stabilizer that fills gaps between phospholipids and modulates fluidity.
4. DSPC (Structural Lipid): Provides the structural integrity and rigidity of the nanoparticle.[21]

The selection of DSPC for this critical application was a strategic choice based on decades of liposome research. The primary challenge in mRNA delivery is the inherent instability of the nucleic acid, which is rapidly degraded by ubiquitous RNase enzymes in the body. The LNP must provide a robust, protective shell. The high  of DSPC ensures that the LNP is in a solid, stable, gel-like state at body temperature. This rigidity physically protects the mRNA from enzymatic degradation and prevents the LNP from prematurely dissociating in the bloodstream. This stability was a key factor in overcoming the historical challenges of nucleic acid delivery and was instrumental in the rapid and successful deployment of these life-saving vaccines. The global success of these products has unequivocally validated DSPC as a gold-standard structural lipid for the systemic delivery of genetic medicines, paving the way for future therapies based on mRNA, siRNA, and CRISPR gene-editing technologies.

Pharmacological Profile and Immunomodulatory Effects

While traditionally viewed as an "inactive" ingredient or a simple carrier, emerging evidence reveals that DSPC can play an active role in modulating the biological and immunological response to a formulation. This understanding shifts the paradigm of excipient selection from a purely physicochemical consideration to one that also encompasses pharmacodynamics and immunology.

Beyond an Inert Excipient: The Adjuvant Properties of DSPC

A pivotal finding is that DSPC-based liposomes, while non-immunogenic when administered alone, can function as a potent immunological adjuvant when used to deliver a vaccine antigen.[23] An adjuvant is a substance that enhances the body's immune response to an antigen, leading to a more robust and durable immunity. The ability of the delivery vehicle itself to contribute to this effect is a significant advantage in vaccine design.

Mechanism of Immune Enhancement

The immunomodulatory activity of DSPC-based liposomes is intrinsically linked to the physical state of their lipid bilayer. A key in vitro study using dendritic cells—the most potent antigen-presenting cells (APCs) of the immune system—demonstrated that gel phase liposomes, which DSPC forms at physiological temperature, are significantly superior to their fluid phase counterparts in augmenting immune activation.[23]

The mechanism of this enhancement involves several key steps in the initiation of an adaptive immune response:

• Enhanced Antigen Presentation: Dendritic cells must process an antigen and present fragments of it on their surface via Major Histocompatibility Complex (MHC) Class II molecules to activate helper T-cells. The study found that gel phase DSPC liposomes were more efficient at facilitating this antigen presentation process compared to both the free antigen and fluid phase liposomes.[23]
• Upregulation of Costimulatory Molecules: T-cell activation requires a second signal, delivered through the interaction of costimulatory molecules on the dendritic cell with receptors on the T-cell. DSPC-based liposomes were found to be superior at upregulating the expression of these critical molecules, specifically CD80 and CD86, on the dendritic cell surface.[23] This enhanced costimulation leads to a more potent T-cell activation.
• Pro-inflammatory Cytokine Release: The activation of dendritic cells is often accompanied by the release of cytokines that shape the ensuing immune response. The study showed that DSPC liposomes led to an increased release of the pro-inflammatory cytokines Interleukin-6 (IL-6) and Interleukin-1β (IL-1β), which help to further amplify and direct the immune reaction.[23]

The physical rigidity of the gel-phase DSPC liposome is likely the root cause of these immunological benefits. A more solid particle may be taken up by dendritic cells through different endocytic pathways or may be processed more slowly within the endolysosomal compartments where antigen processing occurs. This slower, more sustained processing could lead to a more efficient and prolonged loading of antigenic peptides onto MHC molecules, resulting in a more robust and durable presentation to T-cells. This finding transforms the role of the formulation scientist, making the choice of structural lipid a critical decision not just for stability, but for actively tuning the potency and quality of the immune response generated by a liposomal vaccine. This opens a new frontier for the rational design of vaccine delivery systems based on the biophysical properties of their constituent phospholipids.

Pharmacokinetic Profile and Influence on Drug Disposition

The inclusion of DSPC in a nanocarrier formulation fundamentally alters the pharmacokinetic (PK) profile—the absorption, distribution, metabolism, and excretion (ADME)—of the encapsulated drug. By engineering the properties of the delivery vehicle, DSPC allows formulators to control how a drug behaves in the body, often dramatically improving its therapeutic index.

Enhancing Systemic Circulation Time

A primary goal of many advanced drug delivery systems is to prolong the circulation time of the therapeutic agent, allowing for greater accumulation at the target site and reducing the frequency of administration. The choice of phospholipid is a major determinant of a nanocarrier's circulation half-life.

A compelling study that investigated synthetic high-density lipoprotein (sHDL) particles as drug carriers directly compared the impact of different phospholipids on pharmacokinetics. The results were striking: sHDL particles formulated with DSPC demonstrated a circulation half-life of 6.0 hours, a six-fold increase compared to the 1.0-hour half-life of particles made with palmitoyl-oleoyl phosphatidylcholine (POPC), a lipid that is in the fluid phase at body temperature.[34]

Crucially, this dramatic extension in circulation time had a direct and significant therapeutic consequence. The longer-circulating DSPC-based particles resulted in an approximately 6.5-fold increase in the area under the curve (AUC) for the pharmacodynamic effect (in this case, mobilized cholesterol).[34] This provides clear evidence that the stability imparted by DSPC directly translates to enhanced bioavailability and greater therapeutic activity.

Impact on ADME of Encapsulated Agents

By incorporating a drug into a DSPC-based nanocarrier, its pharmacokinetic profile is shifted from that of a small molecule to that of a nanoparticle. This strategic shift has several beneficial consequences for the drug's ADME profile:

• Absorption and Distribution: For intravenously administered drugs, the concept of absorption is bypassed. The key change is in distribution. Free small-molecule drugs often distribute rapidly and non-specifically throughout the body. Encapsulation within a DSPC-based LNP, which is typically around 80-100 nm in diameter, restricts this distribution. The large size of the nanoparticle prevents it from extravasating through the tight junctions of healthy blood vessels and also prevents its filtration by the kidneys.[35] This confinement to the bloodstream is the first step in prolonging circulation.
• Metabolism and Excretion: The nanocarrier acts as a protective shield, protecting the encapsulated drug from degradation by metabolic enzymes in the blood and liver.[33] The primary clearance mechanism for nanoparticles is uptake by the mononuclear phagocyte system (MPS), primarily by macrophages in the liver and spleen.[35] The rigidity and stability of the DSPC-based surface, often combined with a "stealth" coating of polyethylene glycol (PEG), reduces the adsorption of blood proteins (opsonization) that mark the particles for uptake by the MPS. This evasion of the MPS is the primary reason for the dramatically increased circulation times observed.
• Targeting: The prolonged circulation afforded by DSPC-based carriers enhances the probability of the nanoparticle accumulating in pathological tissues, such as solid tumors, through the Enhanced Permeability and Retention (EPR) effect. The leaky vasculature and poor lymphatic drainage characteristic of tumors allow nanoparticles to extravasate and become trapped, leading to passive targeting and a higher concentration of the drug at the site of action.[36]

The bioavailability of DSPC itself is predicted to be zero, as it is not intended to be absorbed as a separate entity.[1] Its function is to remain an integral part of the carrier, thereby fundamentally modifying the bioavailability and disposition of the encapsulated active pharmaceutical ingredient. This strategy can revitalize drugs with otherwise poor pharmacokinetic profiles, extending their therapeutic potential and enabling new clinical applications.

Approved Pharmaceutical Products and Clinical Applications

The theoretical benefits of DSPC have been successfully translated into tangible clinical products approved by regulatory agencies worldwide. Its presence in these formulations provides definitive evidence of its safety, efficacy, and manufacturability as a pharmaceutical excipient.

Ultrasound Contrast Media

DSPC is a key component of LumaSon® (also known as SonoVue® in some regions), an ultrasound contrast agent approved for intravenous and intravesical use.[1] In this product, DSPC is part of a flexible phospholipid shell that encapsulates microbubbles of sulfur hexafluoride gas. When injected into the bloodstream, these microbubbles strongly reflect ultrasound waves, enhancing the echogenicity of blood and improving the visualization of cardiac structures and blood flow. The specific composition of the lipid shell, including DSPC, is critical for the microbubble's stability in circulation and its acoustic response to the ultrasound field.[1]

Liposomal Chemotherapeutics

The field of oncology has long benefited from liposomal drug delivery to improve the therapeutic index of cytotoxic agents. DSPC is a component of DaunoXome®, a liposomal formulation of the anthracycline chemotherapeutic agent daunorubicin.[2] Approved for the treatment of advanced HIV-associated Kaposi's sarcoma, DaunoXome encapsulates daunorubicin within a stable liposome composed of DSPC and cholesterol. This formulation alters the drug's pharmacokinetic profile, leading to a longer circulation time and potentially increased accumulation at tumor sites, while reducing peak plasma concentrations and mitigating some of the severe side effects, such as cardiotoxicity, associated with the free drug.[2]

Vaccines

As detailed previously, DSPC plays a pivotal role as a structural lipid in the LNP delivery systems for the Moderna (Spikevax®) and Pfizer-BioNTech (Comirnaty®) COVID-19 mRNA vaccines.[2] Its inclusion provides the necessary structural integrity to protect the mRNA payload, ensure stability during storage and transport, and contribute to the overall immunogenicity of the vaccine. The global success of these vaccines represents the most widespread and impactful application of DSPC to date.

Table 3: Approved Pharmaceutical Products Containing DSPC

Brand Name	Active Ingredient(s)	Role of DSPC	Indication	Manufacturer
LumaSon®	Sulfur Hexafluoride	Structural component of the gas microbubble shell	Ultrasound contrast agent for echocardiography and other imaging	Bracco Diagnostics Inc.
DaunoXome®	Daunorubicin	Structural component of the liposome bilayer (with cholesterol)	Advanced HIV-associated Kaposi's sarcoma	Gilead Sciences (originally NeXstar)
Comirnaty®	Tozinameran (COVID-19 mRNA)	Structural "helper" lipid in the lipid nanoparticle (LNP)	Prevention of COVID-19	Pfizer-BioNTech
Spikevax®	Elasomeran (COVID-19 mRNA)	Structural "helper" lipid in the lipid nanoparticle (LNP)	Prevention of COVID-19	Moderna

Emerging and Novel Applications

The proven success of DSPC in approved products has spurred extensive research into new therapeutic applications. The versatility and stability of DSPC-based platforms make them suitable for a wide range of future medicines:

• Advanced Gene Therapies: Building on the success of mRNA vaccines, researchers are using DSPC-based LNPs to deliver other nucleic acids, such as small interfering RNA (siRNA) for gene silencing and plasmid DNA for gene replacement therapies.[27]
• Antimicrobial Therapy: Liposomal encapsulation of antibiotics and antifungal agents (e.g., amphotericin B) can improve their therapeutic index by increasing efficacy against intracellular pathogens and reducing systemic toxicity.[40]
• Respiratory Diseases: Inhalable liposomal formulations containing DSPC are being developed for the targeted, sustained delivery of drugs directly to the lungs, which is beneficial for treating diseases like asthma, COPD, and cystic fibrosis.[40]
• Stimuli-Responsive Drug Delivery: A frontier of nanomedicine involves creating "smart" delivery systems that release their payload only in response to a specific trigger. DSPC is being incorporated into novel liposomes designed to become permeable and release their contents when exposed to external stimuli like focused ultrasound or light (photodynamic therapy), or in response to local physiological changes such as lower pH in a tumor microenvironment.[43]

Synthesis, Manufacturing, and Quality Control

The transition of DSPC from a laboratory reagent to a critical component of globally distributed medicines necessitates robust and scalable manufacturing processes, as well as stringent analytical methods to ensure its purity, identity, and consistency.

Production Pathways

Pharmaceutical-grade DSPC can be produced through either semi-synthetic or fully synthetic routes. The choice of method impacts purity, batch-to-batch consistency, and regulatory considerations.

• Semi-synthesis from Natural Sources: One common method involves the extraction of phosphatidylcholines from natural sources like soybeans or egg yolk.[2] These natural extracts contain a mixture of phospholipids with various unsaturated fatty acid chains. Through a process of hydrogenation, the double bonds in these chains are saturated, converting lipids like oleoyl (18:1) and linoleoyl (18:2) chains into stearoyl (18:0) chains. This process can yield a product that is highly enriched in DSPC (e.g., 85%).[2] While cost-effective, this method may result in a product with some variability and residual impurities from the natural source.
• Full Chemical Synthesis: For high-purity applications, particularly for parenteral products like mRNA vaccines, a full chemical synthesis is preferred. This approach provides greater control over the final product's structure, stereochemistry, and purity. Synthetic routes can be complex, often starting from glycerol or a related prochiral precursor. One patented method describes a more streamlined approach starting from a 3-halogenated propylene. This starting material undergoes a chiral catalytic oxidation to create the correct stereocenter, followed by acylation with stearic acid derivatives, and finally, the addition of the phosphocholine head group.[47] This route avoids the multiple protection and deprotection steps required when starting from glycerol, making it more suitable for industrial-scale production.[47] The move toward fully synthetic, chemically defined excipients represents a major trend in the pharmaceutical industry, as it minimizes the batch-to-batch variability that can arise from natural sources and simplifies the regulatory approval process for complex drug products.

Industrial-Scale Production and Suppliers

A robust global supply chain exists for DSPC, with numerous chemical companies specializing in the production of high-purity lipids for pharmaceutical use. These suppliers offer DSPC in various grades, from research-grade to cGMP (current Good Manufacturing Practice)-compliant material suitable for use in clinical trials and commercial drug products.[48] Prominent suppliers include companies like Avanti Polar Lipids (part of Croda Pharma), CordenPharma, and BroadPharm, among many others that provide the material to the global pharmaceutical industry.[19]

In parallel to the synthesis of the lipid itself, advancements are being made in the manufacturing of the final liposomal drug product. Traditional batch methods for liposome preparation, such as thin-film hydration and solvent injection, can be difficult to scale and may lack precise control over particle size.[51] Modern

microfluidic technologies are emerging as a superior alternative. These systems use precisely engineered micro-channels to control the mixing of a lipid-in-organic-solvent stream with an aqueous stream, allowing for the continuous, rapid, and highly reproducible one-step synthesis of liposomes with predictable sizes and high encapsulation efficiencies.[51]

Analytical Methods for Quality Assurance

Ensuring the quality of DSPC is paramount. The purity profile can directly impact the stability and performance of the final drug product.

• Purity Assessment: The primary technique for assessing the purity of DSPC and quantifying impurities is High-Performance Liquid Chromatography (HPLC).[52] Due to the lack of a strong UV chromophore in DSPC, detection is often achieved using an Evaporative Light Scattering Detector (ELSD) or a Charged Aerosol Detector (CAD). Coupling HPLC with Mass Spectrometry (LC-MS) provides even greater specificity for identity confirmation and impurity characterization.[52]
• Identification of Impurities: A well-known and critical impurity in DSPC preparations is its positional isomer, 1,3-distearoyl-glycero-2-phosphocholine (β-lecithin). In this isomer, the phosphocholine head group is attached to the sn-2 position of the glycerol backbone, with the acyl chains at sn-1 and sn-3. This impurity can arise during synthesis or through acyl migration in the final product. Specific chromatographic methods have been developed to separate and quantify this isomer from the desired 1,2-DSPC product, ensuring that the final material meets specifications.[53]

Safety, Toxicology, and Regulatory Status

A comprehensive understanding of the safety and regulatory landscape of an excipient is a prerequisite for its inclusion in any pharmaceutical product. 1,2-Distearoylphosphatidylcholine has an extensive history of safe use and is well-characterized from a toxicological and regulatory perspective, making it a low-risk choice for formulation development.

Comprehensive Toxicological Profile

Toxicological data, primarily derived from safety data sheets (SDS) and toxicology reviews, indicate that DSPC has a very favorable safety profile.

• Acute Toxicity and Irritation: The material is not classified as "harmful by ingestion" by European Community Directives, owing to a lack of corroborating evidence from animal or human studies.[55] It is not considered a skin or eye irritant based on animal models, although direct contact with the eyes as a powder may cause transient physical discomfort, similar to windburn.[55] Inhalation of the powder is not thought to produce adverse health effects or respiratory tract irritation in an occupational setting, though good hygiene practices and dust control are recommended.[55]
• Chronic Toxicity and Carcinogenicity: Long-term exposure is not thought to produce chronic adverse health effects.[55] DSPC is not listed as a carcinogen by major regulatory and research bodies, including the International Agency for Research on Cancer (IARC), the National Toxicology Program (NTP), or the Occupational Safety and Health Administration (OSHA).[57]
• Genotoxicity: Genotoxicity studies, such as the bacterial reverse mutation assay (Ames test), have yielded negative results, indicating that DSPC is not mutagenic.[38]
• Generally Recognized as Safe (GRAS) Status: In the context of inhalation products, lipids like DSPC are considered to be Generally Recognized as Safe (GRAS). This status is based on the fact that these phospholipids are endogenous components of the lung and are present in large quantities as part of the natural pulmonary surfactant.[32] The GRAS provision, as defined by the U.S. FDA, allows for the use of substances in food (and by extension, as excipients) without premarket review, provided they are recognized as safe by qualified experts based on scientific evidence.[61]
• Handling and Safety Precautions: As a fine powder, DSPC dust can form an explosive mixture with air, and appropriate precautions should be taken to avoid dust clouds and ignition sources.[55] Standard personal protective equipment, including safety glasses and gloves, is recommended during handling. The material is incompatible with strong oxidizing agents.[55]

Table 4: Summary of Toxicological and Safety Data

Endpoint	Result/Classification	Comments
Acute Oral Toxicity	Not classified as harmful	Lack of corroborating animal or human evidence.55
Skin Irritation	Not considered an irritant	Based on animal models; good hygiene and gloves recommended.55
Eye Irritation	Not considered an irritant	Direct contact with powder may cause transient physical discomfort.55
Respiratory Irritation	Not considered an irritant	Dust control measures are recommended in occupational settings.55
Carcinogenicity	Not listed as a carcinogen	Not classified by IARC, NTP, or OSHA.58
Mutagenicity	Negative	Found to be non-mutagenic in genotoxicity studies (e.g., Ames test).38
GRAS Status	Considered GRAS for inhalation	Based on its status as an endogenous component of the lungs.38

Regulatory Landscape

DSPC is a well-established excipient with a strong regulatory precedent, which significantly de-risks its use in new drug development programs.

• U.S. Food and Drug Administration (FDA): DSPC is a component of multiple drug products that have received full marketing approval from the FDA. These include the ultrasound contrast agent LumaSon®, the liposomal chemotherapeutic DaunoXome®, and the COVID-19 mRNA vaccines from Pfizer-BioNTech and Moderna.[1] Its inclusion in these approved parenteral products means that DSPC is listed in the FDA's Inactive Ingredient Database (IID) for intravenous administration. This listing provides a clear regulatory pathway for its use in new injectable drug formulations up to the maximum approved dosage level, streamlining the review process.
• European Medicines Agency (EMA): While the provided materials do not contain specific EMA documents pertaining to DSPC, its use in globally approved products like Comirnaty® and Spikevax® means it has been extensively reviewed and accepted by the EMA as part of those marketing authorisation applications. The general framework of the EMA supports the use of innovative and well-characterized excipients in drug manufacturing.[63]

The extensive history of safe use in a variety of approved parenteral products provides a robust foundation for the continued and expanded use of DSPC in next-generation medicines.

Expert Analysis and Strategic Recommendations

1,2-Distearoylphosphatidylcholine has transcended its role as a simple lipid excipient to become a critical enabling technology for some of the most advanced therapeutics of our time. A holistic analysis of its properties reveals not only its strengths but also the challenges and opportunities that will shape its future use. This concluding section synthesizes the key findings of this report to provide forward-looking analysis and strategic recommendations for researchers and formulation scientists.

Current Challenges and Future Directions

Despite its numerous advantages, the optimal use of DSPC involves navigating certain inherent challenges and exploring new frontiers of application.

• The Stability-versus-Release Dilemma: The very property that makes DSPC so valuable—its rigidity and the low permeability of its bilayers—can also be a limitation. While excellent for ensuring a drug remains encapsulated during circulation, this stability can impede the timely release of the drug payload upon reaching the target cell or tissue. For drugs that must act inside a cell, the LNP or liposome must release its contents, often by fusing with an endosomal membrane after uptake. The rigidity of a DSPC-rich membrane can hinder this process. Consequently, a major area of ongoing research is the development of "smart" stimuli-responsive systems. These formulations are designed to be stable and inert in the bloodstream but undergo a phase transition or disruption in response to a specific trigger at the target site. Such triggers include local changes in pH (e.g., the acidic tumor microenvironment), the application of external energy like focused ultrasound or light, or the presence of specific enzymes, thereby enabling on-demand drug release.[43] The future of DSPC lies in its intelligent combination with other lipids or polymers that can confer these triggerable release mechanisms.
• Leveraging Inherent Adjuvant Properties: The discovery that DSPC-based liposomes possess intrinsic adjuvant activity is a paradigm shift. It means that the delivery vehicle is no longer a passive carrier but an active contributor to the efficacy of a vaccine. Future research will undoubtedly focus on elucidating the precise mechanisms behind this effect and learning how to rationally design vaccine adjuvanticity by fine-tuning lipid composition. By systematically varying the ratio of DSPC to other lipids (e.g., those with lower ) or by modifying the surface charge, it may be possible to control the type and magnitude of the immune response (e.g., biasing towards a Th1 vs. Th2 response), tailoring the vaccine for specific pathogens.
• Manufacturing and Global Supply Chain: The unprecedented demand for DSPC during the COVID-19 pandemic highlighted the importance of a robust and scalable manufacturing process. While the supply chain responded effectively, the event underscored the need for continued innovation in both the chemical synthesis of high-purity lipids and the manufacturing of the final LNP drug product. Continuous manufacturing platforms, such as those based on microfluidics, offer a path toward more efficient, scalable, and cost-effective production of lipid nanoparticles with highly controlled and consistent quality attributes.[51] Ensuring a diversified and resilient global supply chain for GMP-grade DSPC will be critical for the future of genetic medicine.

Recommendations for Formulation Scientists and Researchers

Based on the comprehensive profile of DSPC, the following strategic recommendations can be made:

1. For Sustained-Release Parenteral Formulations: DSPC should be considered the gold-standard structural lipid for any application requiring high encapsulation efficiency, minimal drug leakage, and prolonged systemic circulation. Its high  provides a reliable and well-characterized platform for achieving these goals. When developing such formulations, it is crucial to co-formulate with cholesterol to maximize bilayer stability and prevent the formation of undesirable phases.
2. For Intracellular Delivery Applications: When the therapeutic target is intracellular, the inherent rigidity of DSPC must be actively addressed. Formulations should include components designed to facilitate endosomal escape, such as ionizable cationic lipids (which become positively charged in the acidic endosome and disrupt the membrane) or fusogenic lipids (like DOPE). The balance between circulatory stability (favored by DSPC) and intracellular release (favored by fusogenic components) is a critical optimization parameter.
3. For Vaccine Development: Researchers must abandon the view of DSPC as an inert carrier and instead embrace its role as an active immunomodulator. The physical state of the liposome (gel vs. fluid) is a key design parameter for controlling adjuvant activity. Early-stage vaccine development should include studies that correlate lipid composition and phase behavior with immunological readouts, such as dendritic cell activation and T-cell responses.
4. For Regulatory Strategy: The extensive history of DSPC's use in FDA- and EMA-approved parenteral products is a significant asset. In regulatory submissions, developers should explicitly leverage this precedent to de-risk the excipient component of their formulation. It is imperative to maintain meticulous documentation regarding the source, purity, and stereochemical identity (e.g., specifying the use of the sn-glycero-3 form, CAS 816-94-4) of the DSPC used, as this level of precision is now standard for complex drug products.

In conclusion, 1,2-Distearoylphosphatidylcholine is far more than a simple lipid. It is a highly engineered, multifunctional excipient whose unique biophysical properties have been instrumental in solving some of modern medicine's most complex delivery challenges. Its future impact will be defined by its continued use in stabilizing next-generation genetic medicines and by the innovative ways in which scientists learn to harness its more subtle, but equally powerful, immunomodulatory properties.

Works cited

1. 1,2-Distearoyllecithin: Uses, Interactions, Mechanism of Action | DrugBank Online, accessed September 30, 2025, https://go.drugbank.com/drugs/DB14099
2. Distearoylphosphatidylcholine - Wikipedia, accessed September 30, 2025, https://en.wikipedia.org/wiki/Distearoylphosphatidylcholine
3. CAS 4539-70-2: Distearoylphosphatidylcholine - CymitQuimica, accessed September 30, 2025, https://cymitquimica.com/cas/4539-70-2/
4. Distearoylphosphatidylcholine | C44H88NO8P | CID 65146 - PubChem, accessed September 30, 2025, https://pubchem.ncbi.nlm.nih.gov/compound/65146
5. 1,2-Distearoyl-sn-glycero-3-phosphocholine | C44H88NO8P | CID 94190 - PubChem, accessed September 30, 2025, https://pubchem.ncbi.nlm.nih.gov/compound/1_2-Distearoyl-sn-glycero-3-phosphocholine
6. 1,2-Distearoyl-sn-glycero-3-phosphocholine =99 816-94-4 - Sigma-Aldrich, accessed September 30, 2025, https://www.sigmaaldrich.com/US/en/product/sigma/p1138
7. 1,2-Distearoyl-sn-glycero-3-PC - Cayman Chemical, accessed September 30, 2025, https://www.caymanchem.com/product/15100/1-2-distearoyl-sn-glycero-3-pc
8. DISTEAROYLPHOSPHATIDYLC, accessed September 30, 2025, https://precision.fda.gov/ginas/app/ui/substances/7eb7ae80-efee-4071-95cf-3e4acd8ec11d
9. 1,2-Distearoyl-sn-Glycero-3-Phosphatidylcholine | CAS 816-94-4 - Larodan, accessed September 30, 2025, https://www.larodan.com/product/12-distearoyl-sn-glycero-3-phosphatidylcholine/
10. 1,2-Distearoyl-sn-3-phosphacholine - ChemBK, accessed September 30, 2025, https://www.chembk.com/en/chem/1,2-Distearoyl-sn-3-phosphacholine
11. hmdb.ca, accessed September 30, 2025, https://hmdb.ca/metabolites/HMDB0244096#:~:text=1%2C2%2DDistearoyllecithin%2C%20also,each%20through%20an%20ester%20linkage.
12. Showing metabocard for 1,2-Distearoyllecithin (HMDB0244096) - Human Metabolome Database, accessed September 30, 2025, https://hmdb.ca/metabolites/HMDB0244096
13. Distearoylphosphatidylcholine - CAS Common Chemistry, accessed September 30, 2025, https://commonchemistry.cas.org/detail?cas_rn=4539-70-2
14. 4539-70-2|2,3-Bis(stearoyloxy)propyl (2-(trimethylammonio)ethyl) phosphate - BLDpharm, accessed September 30, 2025, https://www.bldpharm.com/products/4539-70-2.html
15. distearoylphosphatidylcholine | C44H88NO8P - ChemSpider, accessed September 30, 2025, https://www.chemspider.com/Chemical-Structure.58655.html
16. DrugRepoBank, accessed September 30, 2025, https://awi.cuhk.edu.cn/~DrugRepurposeDB/php/search_1_result_drugInfo.php?drug_name=1,2-Distearoyllecithin
17. L-A-PHOSPHATIDYLCHOLINE, DISTEAROYL - ChemBK, accessed September 30, 2025, https://www.chembk.com/en/chem/L-A-PHOSPHATIDYLCHOLINE,%20DISTEAROYL
18. DSPC - PRODUCT INFORMATION, accessed September 30, 2025, https://cdn.caymanchem.com/cdn/insert/15100.pdf
19. 18:0 PC (DSPC) | 816-94-4 - Avanti Polar Lipids, accessed September 30, 2025, https://avantiresearch.com/product/850365
20. DSPC | CAS# 816-94-4 | phospholipid - MedKoo Biosciences, accessed September 30, 2025, https://www.medkoo.com/products/43271
21. broadpharm.com, accessed September 30, 2025, [https://broadpharm.com/product/bp-25623#:~:text=DSPC%20(1%2C2%2Ddistearoyl,the%20structure%20of%20lipid%20nanoparticles.](https://www.google.com/url?q=https://broadpharm.com/product/bp-25623%23:~:text%3DDSPC%2520(1%252C2%252Ddistearoyl,the%2520structure%2520of%2520lipid%2520nanoparticles.&sa=D&source=editors&ust=1759232315651308&usg=AOvVaw0nPP82D6N_7Tif1dfB-Vrp)
22. Determination of the Main Phase Transition Temperature of Phospholipids by Nanoplasmonic Sensing - PMC, accessed September 30, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC6172256/
23. Gel Phase 1,2-Distearoyl- sn-glycero-3-phosphocholine-Based ..., accessed September 30, 2025, https://pubmed.ncbi.nlm.nih.gov/31498993/
24. Dipalmitoylphosphatidylcholine - Wikipedia, accessed September 30, 2025, https://en.wikipedia.org/wiki/Dipalmitoylphosphatidylcholine
25. DSPC (1,2-Distearoyl-sn-glycero-3-phosphocholine) - AbMole BioScience, accessed September 30, 2025, https://www.abmole.com/products/dspc.html
26. DSPC (CAS 816-94-4) - R&D Systems, accessed September 30, 2025, https://www.rndsystems.com/products/dspc_7943
27. CAS 816-94-4 DSPC - BOC Sciences, accessed September 30, 2025, https://www.bocsci.com/product/dspc-cas-816-94-4-191720.html
28. Distearoylphosphatidylcholine DSPC - Polysciences, accessed September 30, 2025, https://polysciences.com/products/distearoylphosphatidylcholine-2
29. Targeted drug delivery utilizing protein-like molecular architecture - PMC, accessed September 30, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC2519954/
30. DSPC, 816-94-4 - BroadPharm, accessed September 30, 2025, https://broadpharm.com/product/bp-25623
31. Stabilization of distearoylphosphatidylcholine lamellar phases in ..., accessed September 30, 2025, https://pubmed.ncbi.nlm.nih.gov/24171434/
32. 1,2-Distearoyl-sn-glycero-3-phosphocholine: Uses and Toxicological evaluation, accessed September 30, 2025, https://www.chemicalbook.com/article/1-2-distearoyl-sn-glycero-3-phosphocholine-uses-and-toxicological-evaluation.htm
33. A Comprehensive Review on Liposomes: As Drug Delivery System, accessed September 30, 2025, https://www.ijpsjournal.com/article/A+Comprehensive+Review+on+Liposomes+As+Drug+Delivery+System+
34. Phospholipid Component Defines Pharmacokinetic and Pharmacodynamic Properties of Synthetic High-Density Lipoproteins, accessed September 30, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC6978696/
35. Targeted Liposomal Drug Delivery: Overview of the Current Applications and Challenges, accessed September 30, 2025, https://www.mdpi.com/2075-1729/14/6/672
36. A Review of Liposomes as a Drug Delivery System: Current Status of Approved Products, Regulatory Environments, and Future Perspectives - PubMed Central, accessed September 30, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC8879473/
37. (PDF) A Review of Liposomes as a Drug Delivery System: Current Status of Approved Products, Regulatory Environments, and Future Perspectives - ResearchGate, accessed September 30, 2025, https://www.researchgate.net/publication/358709824_A_Review_of_Liposomes_as_a_Drug_Delivery_System_Current_Status_of_Approved_Products_Regulatory_Environments_and_Future_Perspectives
38. (PDF) Toxicological evaluation of DSPC (1,2-distearoyl-sn-glycero- 3-phosphocholine), accessed September 30, 2025, https://www.researchgate.net/publication/339635899_Toxicological_evaluation_of_DSPC_12-distearoyl-sn-glycero-_3-phosphocholine
39. Journal of Drug Delivery and Therapeutics LIPOSOMAL TOXICITY: A'SEEM TO BE' CONCERN FOR FORMULATION TECHNOLOGISTS, accessed September 30, 2025, https://jddtonline.info/index.php/jddt/article/download/907/557
40. Medical Application of Liposomes - Xia & He Publishing Inc., accessed September 30, 2025, https://www.xiahepublishing.com/2572-5505/JERP-2023-00002
41. Liposomes: structure, composition, types, and clinical applications - PMC, accessed September 30, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9118483/
42. Inflammatory-Targeted Lipid Carrier as a New Nanomaterial to Formulate an Inhaled Drug Delivery System - MDPI, accessed September 30, 2025, https://www.mdpi.com/1420-3049/29/7/1616
43. The Phospholipid Research Center: Current Research in Phospholipids and Their Use in Drug Delivery - PMC - PubMed Central, accessed September 30, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC7766331/
44. A Novel class of Photo-triggerable liposomes containing DPPC:DC8,9PC as Vehicles for Delivery of Doxorubcin to Cells - PMC, accessed September 30, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC2997885/
45. Development of Hybrid DSPC:DOPC:P(OEGMA 950 -DIPAEMA) Nanostructures: The Random Architecture of Polymeric Guest as a Key Design Parameter - MDPI, accessed September 30, 2025, https://www.mdpi.com/2073-4360/15/9/1989
46. The use of natural phospholipids as pharmaceutical excipients Correspondence, accessed September 30, 2025, https://www.pharmaexcipients.com/wp-content/uploads/2020/12/The-use-of-natural-phospholipids-as-pharmaceutical-excipients-vshort.pdf
47. CN103408588A - Preparation method of (R)-1,2-distearoyl phosphatidylcholine - Google Patents, accessed September 30, 2025, https://patents.google.com/patent/CN103408588A/en
48. 1,2-Distearoyl-sn-glycero-3-phosphocholine suppliers & manufacturers in China, accessed September 30, 2025, https://m.chemicalbook.com/ProdSupplierGNCB2724667_EN.htm
49. Avanti™ DSPC - Croda Pharma, accessed September 30, 2025, https://www.crodapharma.com/en-gb/product-finder/product/5828-avanti_1_dspc
50. Lipid: DSPC - CAS #816-94-4 | CordenPharma, accessed September 30, 2025, https://cordenpharma.com/lipid-catalog/phosphocholines/dspc/
51. Rapid, one-step fabrication and loading of nanoscale 1,2-distearoyl-sn-glycero-3-phosphocholine liposomes in a simple, double flow-focusing microfluidic device - PMC - PubMed Central, accessed September 30, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC4491019/
52. CN114740110B - Method for detecting purity of distearoyl phosphatidylcholine - Google Patents, accessed September 30, 2025, https://patents.google.com/patent/CN114740110B/en
53. Isolation of 1,3-distearoyl-glycero-2-phosphocholine (beta-lecithin) from commercial 1,2 ... - PubMed, accessed September 30, 2025, https://pubmed.ncbi.nlm.nih.gov/7354250/
54. Isolation of 1,3-distearoyl-glycero-2-phosphocholine (β-lecithin) from commercial 1,2-distearoyl-sn-glycero-3-phosphocholine - ResearchGate, accessed September 30, 2025, https://www.researchgate.net/publication/15845351_Isolation_of_13-distearoyl-glycero-2-phosphocholine_b-lecithin_from_commercial_12-distearoyl-sn-glycero-3-phosphocholine
55. 1,2-Distearoyl-sn-glycero-3-phosphocholine - Santa Cruz Biotechnology, accessed September 30, 2025, https://datasheets.scbt.com/sc-202871.pdf
56. 1,2-Dioleoyl-sn-glycero-3-phosphocholine - Santa Cruz Biotechnology, accessed September 30, 2025, https://datasheets.scbt.com/sc-208733.pdf
57. Safety Data Sheet - Cayman Chemical, accessed September 30, 2025, https://cdn.caymanchem.com/cdn/msds/15100m.pdf
58. 1,2-distearoyl-sn-glycero-3-phosphocholine - Avanti Polar Lipids, accessed September 30, 2025, https://avantiresearch.com/images/MSDS/AvantiPolarLipids_SDS_770365.pdf
59. Sigma P1138 - SAFETY DATA SHEET, accessed September 30, 2025, https://www.sigmaaldrich.com/IN/en/sds/sigma/p1138
60. Toxicological evaluation of DSPC (1,2-distearoyl-sn-glycero-3-phosphocholine) - J-Stage, accessed September 30, 2025, https://www.jstage.jst.go.jp/article/fts/7/2/7_55/_article
61. Generally Recognized as Safe (GRAS) - FDA, accessed September 30, 2025, https://www.fda.gov/food/food-ingredients-packaging/generally-recognized-safe-gras
62. SAFETY DATA SHEET - Fisher Scientific, accessed September 30, 2025, https://www.fishersci.com/store/msds?partNumber=AC413100010&productDescription=LECITHIN+1KG&vendorId=VN00032119&countryCode=US&language=en
63. EMA Support for Innovation in Pharmaceutical Manufacturing, accessed September 30, 2025, https://ispe.org/pharmaceutical-engineering/ispeak/ema-support-innovation-pharmaceutical-manufacturing
64. EMA Regulatory Science to 2025: Strategic Reflection - ISPOR, accessed September 30, 2025, https://www.ispor.org/docs/default-source/default-document-library/ema-regulatoryscience-summaryofgoals.pdf
65. EMA Overhauls the Medicine Legislative and Regulatory Framework, accessed September 30, 2025, https://www.pharmtech.com/view/ema-overhauls-the-medicine-legislative-and-regulatory-framework