Scientists at Xi'an Jiaotong-Liverpool University (XJTLU) in collaboration with Nanjing University have developed a revolutionary nanoparticle drug delivery system that addresses two critical challenges in cancer treatment: low drug loading capacity and particle instability. Their research, published in ACS Applied Materials & Interfaces, demonstrates a novel coassembly of PLGA polymer with albumin protein that achieves unprecedented drug encapsulation efficiency and stability.
Breakthrough in Drug Loading Capacity
The new supraparticles can encapsulate up to 40% by weight of doxorubicin, a widely used chemotherapeutic agent, representing a dramatic improvement over existing commercial formulations. "One of the most exciting things is that these particles can hold up to 40% of the chemotherapy drug doxorubicin by weight," says Dr Zixing Xu, co-first author and co-corresponding author of the study. "That's a big improvement over some existing treatments, such as Doxil, which hold about 11%. Carrying more drug with less material could help reduce side effects for patients."
This enhanced loading capacity is achieved through a sophisticated coassembly process that leverages the intrinsic properties of both components. PLGA provides a biodegradable scaffold conducive to sustained release, while albumin imparts natural targeting and biocompatibility through non-covalent interactions that form robust supraparticle complexes.
Dual Drug Loading Strategy
The research team explored two distinct methods for drug incorporation, finding that combining both approaches produced superior results. The first method involves incorporating doxorubicin during particle formation, allowing the drug to be encapsulated within the polymer-protein matrix. The second technique involves infusing already formed nanoparticles with the drug by exploiting concentration gradients and solvent interactions. This dual approach synergized the overall loading capacity and optimized drug distribution within the particles.
Enhanced Stability and Targeting
A pivotal finding was the extraordinary colloidal stability exhibited by the supraparticles. While traditional nanoparticle drug carriers suffer from aggregation and premature drug leakage, the albumin-PLGA supraparticles remained physically and chemically stable for over six months under laboratory storage conditions. This durability addresses key hurdles in translating nanomedicine from bench to bedside.
"We managed to solve two big problems at once," explains Dr Gang Ruan, Senior Associate Professor at XJTLU Wisdom Lake Academy of Pharmacy and Director of Jiangsu Province Key Laboratory of Cell Therapy Nanoformulation, who led the research. "These new particles are made by mixing a medical-grade plastic called PLGA with albumin, a protein found in blood. Albumin already plays a role in carrying substances through the body and is used in some current cancer drugs."
Preclinical Validation
Extensive preclinical evaluations demonstrated the therapeutic promise of these supraparticles. In vitro studies utilizing cancer cell lines showed efficient uptake and cytotoxic effects aligned with potent anticancer activity. Complementary in vivo studies in animal models corroborated these findings, showing that the nanoparticles preferentially target malignant tissues while reducing off-target toxicity that often limits chemotherapeutic dosage in clinical settings.
The new delivery system minimized damage to healthy tissues, representing a significant stride toward mitigating debilitating side effects commonly associated with chemotherapy. This selective targeting capability may be attributed to albumin's role in exploiting endogenous transport pathways such as albumin receptor-mediated endocytosis.
Manufacturing and Commercial Viability
From a pharmaceutical manufacturing standpoint, preliminary scale-up studies indicate that these protein-polymer supraparticles can be produced reproducibly without compromising particle uniformity or functionality. This consistency in nanoparticle size, drug loading, and release kinetics represents critical quality attributes required by regulatory bodies for commercial viability.
Future Applications
The modular nature of the coassembly process could facilitate loading of diverse drugs beyond doxorubicin, including biologics, nucleic acids, or combination therapies. The platform's ultrahigh colloidal stability could enable more flexible dosing schedules, patient-friendly administration routes, and the development of novel formulations such as injectable gels or inhalable aerosols.
This development marks a significant milestone in nanomedicine, where hybrid materials synthesized via bioinspired assembly unlock new frontiers in therapeutic delivery. By bridging material science with molecular biology, the research team has charted a path toward safer, more effective treatments that harness the body's natural biological machinery in concert with engineered polymers.
