Novel Enhanced Therapeutic Efficacy of Dapoxetine HCl by Nano-Vesicle Transdermal Gel for Treatment of Carrageenan-Induced Rat Paw Edema

Novel Enhanced Therapeutic Efficacy of Dapoxetine HCl by Nano-Vesicle Transdermal Gel for Treatment of Carrageenan-Induced Rat Paw Edema:

Abstract

The aim of this was to develop a well-balanced, replaceable, and patient non-infringing innovative transdermal drug delivery system “nano-vesicle transdermal gel” (NVTG) approaches for inhibiting inflammation. To consummate this objective, we developed a skin permeation nanogel system containing surface active agent along with ethanol. Carbopol 971p, hydroxypropyl methyl cellulose (HPMC K15M), and chitosan were used to fabricate the nanogels. The nanogel system was evaluated for pH, content uniformity, spreadability, rheological studies, in vitro skin permeation, and drug release. Carbapol 971p with the desired in vitro skin permeation was utilized to investigate skin irritation test and effects on inflammation using acute inflammatory paw edema models. Moreover, in vivo pharmacokinetic study was assessed. pH of this nanogels was found within the range of 6.1–7.2, whereas the viscosity was found 310.13 to 6361 cps. The ex vivo skin permeation gels showed permeation flux range, 5.9 ± 0.80 to 17.92 ± 1.13 μg/cm² h. The highest permeation flux (17.92 ± 1.13 μg/cm² h) was observed, which was 3.14-folds higher than that of the plain DH gel (10.72 ± 0.84 μg/cm² h. Additionally, from toxicological study, no obvious signs of toxicity such as skin irritation (of laboratory rats) were identified. The in vivo anti-inflammatory behavior in carrageenan-induced rats showed comparatively higher inhibition of rat paw edema swelling by the prepared nanogel compared to that of the plain DH gel and marketed ibuprofen over 6 h. The amount of drug accumulated in the skin after topical application was much higher than oral application. In conclusion, developed NVTG formulation loaded with dapoxetine HCl (DH) offers new opportunities for creating novel therapeutic modality for inflammation patients with fewer adverse effects.