Colchicine mesoporous silica nanoparticles/hydrogel composite loaded cotton patches as a new encapsulator system for transdermal osteoarthritis management

Abstract

Colchicine is a drug from the past with a bright shining future. It has gained much attention nowadays due to the newly explored therapeutic avenues that were opened by its application in serious ailments. Colchicine has been recently observed as a potential treatment for osteoarthritis (OA). OA is a widespread joint degenerative disease that causes extensive pain and disability. Colchicine has been discovered to affect bone turnover and to reduce different cytokines like interleukin 6 (IL6). Colchicine oral administration has several limitations including extensive first-pass effect, poor bioavailability, and severe GIT side effects. The transdermal route circumvents these limitations. However, colchicine transdermal delivery is challenging owing to its high aqueous solubility and hence poor skin permeation. In this study, novel colchicine transdermal delivery systems were developed to conquer such obstacles. Cellulose-based patches were primed, where mesoporous silica nanoparticles (MSNs) were prepared and used as colchicine encapsulators. The free colchicine or the encapsulated drug was embedded into self-healing hydrogel. The hydrogel was prepared by reacting carboxyethyl chitosan and oxidized pullulan. These composites were used to treat cotton fabric to produce easily applicable and extended-release transdermal patches. Nitrogen adsorption-desorption isotherms, DLS, TEM, and SEM were used to estimate surface area, pore-volume, size, zeta potential, and morphology of MSNs. The hydrogel was characterized using FTIR and TEM. The prepared cotton patch was tested for fabric stiffness. Ex vivo drug permeation study through isolated rat skin was conducted. In comparison to free drug aqueous solution, the patches revealed enhanced drug flux and amplified permeated drug levels which were sustained all over 24 h. Skin permeation was further validated via confocal laser microscopy using fluorescein. The therapeutic investigation of colchicine formulated patches in mono-iodoacetate (MIA)-induced rat osteoarthritis model depicted improved locomotor activity, glutathione blood level, and remarkable decline in levels of malondialdehyde, nitric oxide, TNF-α, and COX-2. Histopathology of rats knee joint supported the OA protective effect of the developed patches, The obtained results revealed significant potentiality of the developed colchicine mesoporous silica nanoparticles/hydrogel patches in the offering, efficient safe and patient convenient formulation for OA management.

Keywords: Chitosan; Colchicine; Cotton fabric; Hydrogel; Mesoporous silica nanoparticles; Osteoarthritis; Pullulan; Transdermal.