The Hassanuddin University team systematically reviewed the obstacles and strategies for drug delivery in oral squamous cell carcinoma, emphasizing validation in real-world clinical settings.

Hassannudin University reports that delivering cancer drugs directly to oral tumors sounds like a more precise treatment approach with fewer systemic side effects, but the mouth is not a quiet window for drug delivery. Saliva rinsing, chewing and swallowing, speaking and tongue movements, as well as the morphology and location of the tumor itself, all make it difficult for drugs to remain at the lesion and be released stably. A recent review published by researchers at Hassannudin University points out that local drug delivery systems must be matched to the specific circumstances of the drug, the tumor, and the patient, and tested under near-real-world clinical conditions.

This review was led by Professor Nurhasni Hassan of the Faculty of Pharmacy, Hassanuddin University, Indonesia, with a team from Indonesia, Japan, and China. The article focuses on oral squamous cell carcinoma (OSCC)—one of the most common malignant tumors of the oral cavity and head and neck, and a significant contributor to global cancer incidence and mortality. The review was published online on May 21, 2026, and formally published in Volume 225 of the *European Journal of Pharmaceutics & Biopharmaceutics* on August 1, 2026.

The oral environment constitutes a "hard constraint".

The advantage of local treatment lies in increasing drug exposure at the tumor site while reducing drug exposure to other organs throughout the body. However, the authors emphasize that the oral environment continuously interferes with drug absorption, creating a "hard limitation" to effective local delivery. Saliva dilutes and washes away the drug, while enzymes, chewing, speaking, and tongue movements can disrupt or dismantle the delivery system. This means that the drug not only needs to be "delivered," but also "retained and stabilized."

This review summarizes various strategies for the local treatment of OSCC, including mucosal adhesive membranes and patches, oral sprays, in-situ gels, and injectable hydrogels. The researchers do not believe there is a universal solution, but rather emphasize that the optimal delivery system depends on the drug and tumor characteristics.

For example, in cases where the lesion is flat and easily palpable, mucosal adhesion membranes have an advantage: they can adhere to the mucosal surface while releasing the drug. For irregularly shaped or infiltrative lesions, gels or injectable hydrogels may be more suitable because they can conform to complex tissue surfaces, providing longer-lasting drug exposure and penetrating deeper into the tissue layers. Sprays are convenient to use, but their residence time is often shorter due to the influence of saliva clearance.

The oral environment will also change during treatment.

The review also notes that cancer treatments themselves alter the oral environment. Radiation and chemotherapy often cause dry mouth and mucosal damage, which in turn affect oral hydration, lubrication, drug release, and adhesion. Increased saliva flow also accelerates drug dilution and clearance. Therefore, formulations that perform well under simplified laboratory conditions may have different effects after entering the patient's body

The research team therefore calls for a more realistic evaluation of local delivery systems. Future research should focus on the ability of formulations to maintain adhesion under saliva flow and mechanical stress, their stability under changes in pH and enzyme activity, and their ability to sustainably deliver drugs to tumor margins. The review also assessed the translational maturity of different formulations.

Professor Hassan points out that the academic community tends to reduce drug delivery problems to "developing better formulations," but the real key question is whether such a formulation is suitable for a specific clinical scenario. She cautions that if a cutting-edge technology faces obstacles in production, use, or tolerability, its clinical value will be very limited, and practical factors should be considered from the early stages of research and development.

Near-term potential and long-term challenges coexist

From a translational perspective, mucosal adhesive membranes and patches appear to have greater near-term development potential, as similar oral delivery methods already have regulatory and manufacturing precedents. Hydrogels for injection offer a promising option for irregular lesions, but challenges remain regarding production, gelation, degradation, clinical application, and long-term biocompatibility.

It is worth noting that these technologies have not yet become mature treatments for OSCC. Therefore, this review proposes a framework to advance promising approaches to clinical practice by matching delivery systems with drugs, tumors, and individual patient circumstances.

Researchers concluded that the design goal of next-generation local oral cancer therapies should not merely be "drug delivery," but rather ensuring that the appropriate amount of drug acts on the appropriate site at the appropriate time. Professor Hassan stated that local treatment should become more predictable, with delivery systems that are easy for researchers to continuously evaluate and also practically usable by clinicians.