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 via PubMed
Summary
AI-generated from the abstractA thermosensitive mucoadhesive hydrogel for nasal delivery of the psychedelic drug 5-methoxy-N,N-dimethyltryptamine was developed using a mixture of Poloxamer 407, Poloxamer 188, and Hydroxypropyl-methylcellulose. A Box-Behnken experimental design optimized gelification temperature, viscosity, and mucoadhesion to increase contact time with nasal mucosa while preserving ciliary function. The final formulation gels at around 32 °C, has a viscosity near 100 mPas, and mucoadhesion of about 4.20 N·m. In vitro testing showed sustained release, with 73.76% of the drug delivered after 5 hours. Raman spectroscopy confirmed homogeneous mixing of drug and polymers. The formulation may enable future studies for treating certain mental disorders.
Study at a glance
| Characteristics | Experimental study with 3 × 3 Box-Behnken design Peer reviewed |
|---|---|
| Intervention | 5-methoxy-N |
| Duration | 5 hours in vitro release |
| Keywords | Drug delivery systems Nasal drug administration Thermosensitive polymers Pharmaceutical formulations Controlled release technology |
| Citations | 5 |
| Key finding | The optimized thermosensitive mucoadhesive hydrogel achieves sustained release of 73.76% of the drug after 5 hours in vitro, with a gelling temperature around 32 °C, viscosity near 100 mPas, and mucoadhesion of about 4.20 N·m. |
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.