Chitosan-Graft-Poly(N-Isopropylacrylamide)/PVA Cryogels as Carriers for Mucosal Delivery of Voriconazole

Abstract

The objective of this study was to prepare and characterize physically crosslinked gel formulations of chitosan (CS)-graft-poly(N-isopropyl acrylamide) (PNIPAAm) and polyvinyl alcohol (PVA) for smart delivery of an antifungal drug, Voriconazole, for mucosal applications. For this purpose, cryogels of CS-g-PNIPAAm/PVA and CS/PVA were tested by means of texture profile analysis and rheology to determine optimal matrix properties for topical application. The ratio of 75/25 v/v % CS-g-PNIPAAm/PVA was selected to be used for formulation since it gave low compressibility and hardness (1.2 and 0.6 N) as well as high adhesion properties and non-Newtonian flow behavior. The cryogels and formulations were further characterized by means of FTIR spectroscopy, swelling behavior, texture analysis, scanning electron microscopy (SEM), thermal (differential scanning calorimetry (DSC) and TGA), and rheological behavior. The drug loading capacity and in vitro release profile of the drug, storage stability, and cytotoxicity tests were also performed for the gel formulation. The FTIR, DSC, and TGA results verified the successful formation of cryogels. Swelling studies revealed a pH-dependent swelling ability with a maximum swelling degree of 1200% in acid and 990% in phosphate buffer (pH = 7.4). Thermal studies showed that CS-g-PNIPAAm/PVA 75/25 had higher thermal stability proving the structural complexity of the polymer. The loading capacity of Voriconazole was found to be 70% (w/w). The in vitro release profiles of Voriconazole showed Fickian release behavior for CS-g-PNIPAAm/PVA 75/25 gel with an approximate delivery of 38% within 8 h, slower than matrices containing unmodified chitosan. The storage stability test exhibited that the gel formulation was still stable even after aging for two months. Moreover, the cell culture assays revealed a non-toxic character of the polymeric matrix. Overall results showed that the CS-g-PNIPAAm/PVA 75/25 hydrogel has the potential to be used as a smart polymeric vehicle for topical applications.

On the Development of Chitosan-Graft-Poly(n-Isopropylacrylamide) by Raft Polymerization Technique

“…Thermal stability, together with the ability to respond to pH and temperature, allowed the use of CS-g-PNIPAAm as part of a hydrogel pharmaceutical formulation for topical application. 17 Hydrogels based on Cs-g-PNIPAAm presented, alongside pH and temperature responsivity, bioadhesivity and nontoxicity, thus being suitable for topical drug delivery systems. Other modified chitosan based hydrogels were also found suitable for topical application, the evidence being the number of studies performed in this field.…”

“…Other modified chitosan based hydrogels were also found suitable for topical application, the evidence being the number of studies performed in this field. [17][18][19][20]…”

Biocompatible non-covalent complexes of chitosan and different polymers: Characteristics and application in drug delivery

“…However, they are formed mainly by the formation of hydrogen bonds between hydroxyl or amino groups of chitosan and hydroxyl groups of PVA (1). They can be readily prepared using different methods, such as the autoclaving method (98) and the freeze/thaw method (99)(100)(101). The structure of complexes could be different depending on the preparation method.…”

“…The complexes prepared by the autoclaving method are formed by mixing and autoclaving the PVA and chitosan dispersions to form highly elastic hydrogels (98). Hydrogels obtained by the freeze/thaw method are formed by repeating the freezing and thawing cycles of chitosan and PVA dispersions (99)(100)(101). Complexes prepared by the autoclaving method can be dissolved under acidic conditions and are not suitable as drug carriers.…”

Emerging trends in nanomedicine for topical delivery in skin disorders: Current and translational approaches

“…15 F I G U R E 1 The microscopic structure of the skin F I G U R E 2 Mechanistic absorption routes from topical drug delivery systems Nanoparticles have been studied and evaluated for several biomedical applications. [19][20][21][22][23][24] These drug delivery systems enhance drug absorption and allow sustained release for a longer duration. The nanocarriers also protect encapsulated drug material from chemical degradation.…”