Next-Gen Local Drug Delivery: Rethinking Oral Cancer Care
核心洞察
A review led by Professor Nurhasni Hasan of Hasanuddin University (搜索) examines how local drug delivery systems can overcome barriers in treating oral squamous cell carcinoma (搜索) (OSCC).
The mouth's saliva, enzymes, chewing, and tongue movement create "hard constraints" that dilute, degrade, or dislodge medicines at the tumor site.
Researchers argue no single formulation suits every tumor, recommending delivery systems be matched to the drug, tumor location and shape, and individual patient needs.
Delivering drugs directly to oral tumor sites remains a persistent challenge, and a new review led by Professor Nurhasni Hasan of the Faculty of Pharmacy, Hasanuddin University (搜索), Indonesia, examines how emerging local drug delivery systems could be designed to overcome the barriers in treating oral squamous cell carcinoma (搜索) (OSCC). OSCC is one of the most common malignancies affecting the oral cavity and head and neck region, and one that contributes significantly to the global burden of cancer-related morbidity and mortality.
The review, made available online on May 21, 2026, and published in Volume 225 of the European Journal of Pharmaceutics and Biopharmaceutics on August 1, 2026, brings together researchers from Indonesia, Japan, and China. It analyzes a range of local treatment approaches, including mucoadhesive films and patches, oral sprays, in-situ gels, and injectable hydrogels.
The "Hard Constraints" of the Oral Cavity
Treating oral cancer with drugs delivered directly to the lesion site is a promising approach, requiring that the medicine remain at the cancer site long enough to provide sustained treatment—facilitating increased drug exposure to the tumor while reducing unwanted exposure throughout the body. However, the mouth is constantly working against the medicine, creating what the authors describe as stringent "hard constraints" for effective local drug delivery.
Saliva can dilute and wash away medicines, while enzymes, chewing, speaking, and tongue movement can degrade or dislodge drug-delivery systems used for treatment. These physiological forces fundamentally limit how long a medicine remains at the treatment site and how consistently it is released.
Matching the Delivery System to the Tumor
Rather than treating these technologies as one-size-fits-all solutions, the researchers emphasize that the best delivery system may depend on the characteristics of both the drug and the tumor.
"There is a tendency to think of drug delivery as a problem that can be solved by developing a better formulation," explains Prof. Hasan. "However, the bigger question is whether the formulation is appropriate for that particular clinical situation."
Depending on the shape and location, a flat, accessible lesion would be suitable for mucoadhesive films that remain attached to the mucosa while delivering the drug. In contrast, lesions that are irregular or infiltrative may benefit from gels or injectable hydrogels that can conform to complex tissue surfaces and provide more sustained drug exposure, delivering the drug to deeper layers. Sprays are comparatively convenient in application but have shorter residence time due to salivary clearance.
A Changing Environment During Treatment
The oral environment also undergoes changes during cancer treatment. Radiotherapy and chemotherapy often result in xerostomia, or dry mouth, and mucosal damage, affecting hydration, lubrication, drug release, and adhesion. An increase in salivary flow leads to acceleration in dilution and clearance, indicating that formulations tested under simplified laboratory conditions may not perform in the same way in patients.
The researchers therefore call for a more realistic evaluation of local drug-delivery systems. They emphasize that future studies should focus on how well formulations remain attached under salivary flow and mechanical stress, maintain stability against changes in pH and enzymatic activity, and deliver drugs consistently to tumor margins.
Translational Maturity and Clinical Potential
The review also assessed the translational maturity of different types of formulations. Mucoadhesive films and patches currently appear to have stronger near-term potential because similar buccal delivery formats already have regulatory and manufacturing precedent. Injectable hydrogels, on the other hand, offer promising options for irregular lesions but face additional challenges involving manufacturing, gelation, degradation, clinical application, and long-term biocompatibility.
"A sophisticated technology has limited clinical value if it is difficult to manufacture, administer, or tolerate. These practical considerations must guide formulation development from the start," notes Prof. Hasan.
Notably, these technologies are not yet established treatments for OSCC. The review provides a framework for moving promising approaches toward clinical use by matching the delivery system to the drug, tumor, and conditions experienced by the individual patient.
Taken together, the researchers suggest that the next generation of local oral cancer therapies should be designed to keep the right amount of drug at the right place for the right length of time—and not merely for drug delivery. "The goal should be to make local treatment more predictable. We need delivery systems that researchers can evaluate consistently and clinicians can realistically use," concludes Prof. Hasan.