Amylose/Amylopectin Patch for Intraoral Release of Mucoadhesive Valsartan From Dentures

Objectives: Valsartan is an angiotensin receptor blocker used for hypertension control in the elderly and potential management of SARS-CoV-2 virus infection. However, the therapeutic performance of valsartan is limited by low solubility and gastric-intestine-only uptake. This study aimed to develop a biodegradable patch to promote the release of mucoadhesive valsartan-conjugated chitosan from prosthesis bases.
Methods: Valsartan-chitosan was synthesized by amide coupling (1-hydroxybenzotriazole/1-ethyl-3-carbodiimide) and characterized by infrared spectroscopy (IR) and nulear magnetic resonance. The mucoadhesion was confirmed via mucin particle assay. The mechanical properties (max tensile force, elastic modulus, flexural modulus, n=8) of the amylose/amylopectin patch were optimized by adjusting the glycerol (10/20 wt%), citric acid (0.74/1.48 wt%) and chitosan (5/10/15 wt%) content. The functionality of patches was assessed by enzymatic degradation and drug release with dentures in artificial saliva containing α-amylase (pH=6.8, 37 °C, 4 h, n=3). Statistical analyses were conducted by two-sample t-test with a global significance level of 5%.
Results: The amide conjugation of valsartan to chitosan was confirmed by IR without compromising mucoadhsivity (zeta-potential +11.32 mV for chitosan-modified mucin and +10.27 mV for valsartan-chitosan-modified mucin). Among all compositions, the patch containing 20% glycerol and 0.74% citric acid presented flat surface, higher flexibility (flexural modulus 57.7 MPa vs 86.6-204.5 MPa) and lower tensile strength (max force/elastic modulus 12.2 N/18.0 MPa vs 13.0-19.2 N/18.5-26.9 MPa). Patch with 10% chitosan, 2.5% drug loading and medium mechanical performance was selected. When applied to denture bases, patches (0.075 mg valsartan per mm2) yielded 55% cumulative drug release in 1 h and degradation in 1.5 h.
Conclusions: We developed a biodegradable patch with mechanical properties that can be applied to denture bases and promote the delivery of mucoadhesive valsartan loaded. Drug release from the patch allows for drug dosage by fine-tuning patch geometry, making it suitable for controlled drug delivery to elderly patients.