Toxicity and efficacy studies of clobetasol and methotrexate loaded nanogels for the treatment of psoriasis

Abstract

Use of nanodrug delivery systems for improved skin penetration and better skin localization is found to be beneficial for effective topical delivery of drugs, for which stratum corneum permeability is a limiting factor. Research works in the field of nanotechnology have introduced the need for developing nanogel systems which prove their potential to deliver drugs in controlled, sustained and targetable manner. By selecting appropriate polymers it is possible to modify the surface charge of the nanogel system and thus control the interaction with skin and hence the transdermal flux. In addition, the gel like consistency of nanogel achieved through the use of suitable polymers makes it skin compatible and ideal for topical use. In the present work, we used chitin based nanogel system for topical delivery of two anti-psoriatic drugs clobetasol and methotrexate. It is expected that the rich OH and NHCOCH3 functionalities present in the chitin will help for effective interaction of selected drugs with the polymer, resulting in better loading of the drugs into the nanogel system. Also we used 72% acetylated chitin, as in remaining 28% of monomers, the -NH2 groups are free which may provide an overall positive charge to the developed system. This positive charge helps to interact with keratinocytes of skin and may provide improved drug permeation. Also the greater drug retention in deep layers of epidermis and dermis offered by chitin nanogel system will provide additional benefits as these are the major sites involved in psoriasis pathology. In the first part of the work, the chitin nanogel loaded with selected anti-psoriatic drugs, clobetasol loaded chitin nanogel (CLCNG) and methotrexate loaded chitin nanogel (MCNG) was prepared by using simple regeneration chemistry. The prepared nanogels were characterized by DLS, TEM and FTIR. Both CLCNG and MCNG are showing nanosize with cationic charge. Various in vitro evaluations such as swelling studies, drug release studies, skin permeation ( abstract attached).