Novel Thermosensitive and Mucoadhesive Nasal Hydrogel Containing 5-MeO-DMT Optimized Using Box-Behnken Experimental Design.
Pablo Miranda, Analía Castro, Paola Díaz, Lucía Minini, Florencia Ferraro, Erika Paulsen, Ricardo Faccio, Helena Pardo
Polymers July 29, 2024 DOI: 10.3390/polym16152148
Summary
Scientists have developed a breakthrough nasal gel that transforms from liquid to gel at body temperature, allowing precise delivery of therapeutic compounds. This smart delivery system combines specialized polymers (Poloxamer 407, Poloxamer 188, and HPMC) to create an intranasal formulation that sticks to nasal tissue and releases medicine gradually. The gel shows impressive sustained release, delivering 74% of its therapeutic content over 5 hours while maintaining normal nasal function.
Abstract
We present the development and characterization of a nasal drug delivery system comprised of a thermosensitive mucoadhesive hydrogel based on a mixture of the polymers Poloxamer 407, Poloxamer 188 and Hydroxypropyl-methylcellulose, and the psychedelic drug 5-methoxy-N,-N-dimethyltryptamine. The development relied on a 3 × 3 Box-Behnken experimental design, focusing on optimizing gelification temperature, viscosity and mucoadhesion. The primary objective of this work was to tailor the formulation for efficient nasal drug delivery. This would increase contact time between the hydrogel and the mucosa while preserving normal ciliary functioning. Following optimization, the final formulation underwent characterization through an examination of the in vitro drug release profile via dialysis under sink conditions. Additionally, homogeneity of its composition was assessed using Raman Confocal Spectroscopy. The results demonstrate complete mixing of drug and polymers within the hydrogel matrix. Furthermore, the formulation exhibits sustained release profile, with 73.76% of the drug being delivered after 5 h in vitro. This will enable future studies to assess the possibility of using this formulation to treat certain mental disorders. We have successfully developed a promising thermosensitive and mucoadhesive hydrogel with a gelling temperature of around 32 °C, a viscosity close to 100 mPas and a mucoadhesion of nearly 4.20 N·m.