A water-soluble, mucoadhesive quaternary ammonium chitosan-methyl-β-cyclodextrin conjugate forming inclusion complexes with dexamethasone

The ocular bioavailability of lipophilic drugs, such as dexamethasone, depends on both drug water solubility and mucoadhesion/permeation. Cyclodextrins and chitosan are frequently employed to either improve drug solubility or prolong drug contact onto mucosae, respectively. Although the covalent conjugation of cyclodextrin and chitosan brings to mucoadhesive drug complexes, their water solubility is restricted to acidic pHs. This paper describes a straightforward grafting of methyl-β-cyclodextrin (MCD) on quaternary ammonium chitosan (QA-Ch60), mediated by hexamethylene diisocyanate. The resulting product is a water-soluble chitosan derivative, having a 10-atom long spacer between the quaternized chitosan and the cyclodextrin. The derivative is capable of complexing the model drug dexamethasone and stable complexes were also observed for the lyophilized products. Furthermore, the conjugate preserves the mucoadhesive properties typical of quaternized chitosan and its safety as solubilizing excipient for ophthalmic applications was preliminary assessed by in vitro cytotoxicity evaluations. Taken as a whole, the observed features appear promising for future processing of the developed product into 3D solid forms, such as controlled drug delivery systems, films or drug eluting medical devices

Smart hydrogel for the pH-selective drug delivery of antimicrobial compounds

Infection is a major prompt of chronic wounds, increasing the pH on the injury tissues. Thus, pH can be used as trigger for antimicrobial agents' delivery, preventing chronic wounds. Hence, the present work aimed to develop a hydrogel with drug delivery capacity, modulated by environmental pH. Chitosan was used as electrolyte monomer and it was crosslinked with hydroxypropyl methylcellulose and 2-hydroxypropyl-beta-cyclodextrin. The polymeric network assembly was confirmed by FTIR and thermal analysis. The developed hydrogels behaved as superabsorbent systems, with higher swelling at pH 7. Caffeic acid loading was ruled by the inclusion complex formation between the phenolic acid and cyclodextrin. Chitosan hydrogels delivery capacity was pH-dependent and, also, more efficient at pH 7. Based on the Peppas-Sahlin model, fickian diffusion was the main mechanism responsible for caffeic acid release. Based on the results, the developed hydrogel can be used to prevent wound infection, due to its ability to release antimicrobial agents when the wound pH rises.This article is a result of the project TSSiPRO-NORTE-01-0145-FEDER-000015-supported by the regional operational program NORTE 2020, under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund. The authors, also, wishing to acknowledge the Project UID/CTM/00264/2019 of 2C2T - Centro de Ciencia e Tecnologia Textil, funded by National Founds through FCT/MCTES