Formulation of pH-Sensitive Nanogels of Fluocinolone Acetonide for the Treatment of Psoriasis

Background and Aim: The word “Psoriasis” is derived from the Greek words meaning “an itching condition”. It is a chronic inflammatory multi-organ disease known to be the most prevalent autoimmune disease in humans. Currently available therapies for the treatment of psoriasis are either cosmetically unacceptable, require repeated administration or linked with significant adverse toxicity. Due to differences in the pH on the surface of healthy skin (pH 5.0-6.0) and at the psoriatic lesions (pH 4.0-5.0), pH-sensitive nanogels are an intelligent candidate for the treatment of psoriasis. N, N, N- Trimethyl Chitosan (TMC) is a quaternized derivative of chitosan (CS) with superior solubility over pH range 1-9, increased permeation, mucoadhesiveness and pH-stimulus properties. The aim of this study is to develop pH-sensitive nanogels (designated as FA-NG) containing the widely used anti-psoriatic drug Fluocinolone Acetonide (FA) and TMC as the polymeric carrier.

Methods: TMC was first synthesised in the laboratory from the widely available and economical polymer CS by a single step methylation reaction using methyl iodide and N-methyl pyrrolidone (NMP). FA-NGs were prepared by chemical cross-linking method using glutaraldehyde as the cross-linker. TMC solutions with different concentrations were prepared in deionised water and subjected to overnight stirring to ensure complete uniformity of the polymer. To the TMC solution, the drug Fluocinolone Acetonide dissolved in PEG 400 was added drop wise with constant stirring to allow for the proper loading of the drug in the gel and then sonicated for different times. The gels were then crosslinked by the addition different concentrations of 25% w/v aqueous Glutaraldehyde solution and stirred well to form the nanogels.

Results: FA-NGs were prepared by chemical cross-linking method using glutaraldehyde as the cross-linker.

Conclusions: FA was effectively entrapped in the FA-NG using chemical cross-linking method. TMC is a promising future candidate as a polymer for novel drug delivery systems. FA-NG can prove to be an ideal and novel candidate for treatment of psoriasis.

1. Conversion of CS to TMC

2. Development of FA-NG (Mourya et al., 2009, Oha et al., 2009, Rao et al., 2013).