A Novel Chitosan Nanosponge as a Vehicle for Transepidermal Drug Delivery.

Jin Sil Lee,Yong Chul Shin,Hyeryeon Oh,Jeung-Hoon Lee,Sunghyun Kim,Won Il Choi

doi:10.3390/pharmaceutics13091329

Abstract

Transepidermal drug delivery achieves high drug concentrations at the action site and ensures continuous drug delivery and better patient compliance with fewer adverse effects. However, drug delivery through topical application is still limited in terms of drug penetration. Chitosan is a promising enhancer to overcome this constraint, as it can enhance drug diffusion by opening the tight junctions of the stratum corneum. Therefore, here, we developed a novel chitosan nanosponge (CNS) with an optimal ratio and molecular weight of chitosan to improve drug penetration through skin. To prepare the CNS, two types of chitosan (3 and 10 kDa) were each conjugated with poloxamer 407 using para-nitrophenyl chloroformate, and the products were mixed with poloxamer 407 at ratios of 5:5, 8:2, and 10:0. The resulting mixtures were molded to produce flexible soft nanosponges by simple nanoprecipitation. The CNSs were highly stable in biological buffer for four weeks and showed no toxicity in human dermal fibroblasts. The CNSs increased drug permeability through human cadaver skin in a Franz-type diffusion cell, with substantially higher permeability with 3 kDa chitosan at a ratio of 8:2. This suggests the applicability of the novel CNS as a promising carrier for efficient transepidermal drug delivery.

Highlights

Published: 25 August 2021Percutaneous drug delivery has been a major focus of many studies to identify alternative drug administration pathways
Chitosan-poloxamer conjugates were produced in two steps
The synthesis of activated poloxamer and chitosan-poloxamer conjugates was confirmed to be above 98%, based on 1 H-NMR spectroscopy (Figure 2), with which methyl protons (1.07 ppm; 3) of the poly(propylene oxide) block in the poloxamers, the proton in para-nitrophenyl chloroformate (8.21 ppm; 1), and the anomeric protons in chitosan (4.51 ppm) were analyzed [31]

Summary

Introduction

Percutaneous drug delivery has been a major focus of many studies to identify alternative drug administration pathways. Numerous studies have examined various transepidermal drug delivery systems, including lipid-based vehicles, vesicular carriers, particulate lipid carriers, surfactant-based nanocarriers, transfersomes, and polymer-based nanoparticles [5,6,7,8]. Lin et al developed lipid-based vesicles to increase the skin permeation of drugs; these vesicles were produced using thin-film hydration, and cationic surfactant-modified ultradeformable liposomes used in the vesicles increased drug release and improved transepidermal flux [9]. Soft lipid-based nanotransfersomes containing eprosartan mesylate were examined, and optimized nanotransfersomes helped achieve enhanced transepidermal flux through Wistar rat skin [10]. The thermoresponsive activity of the triblock polymer nanoparticles promoted the diffusion of drugs into the stratum corneum [11]. Most drugs are limited with respect to their diffusion ability

Methods

Results

Conclusion