Formulation, optimization, and in-vitro evaluation of polymeric microsponges for topical delivery of vanillin

Abstract

The development of ethylcellulose-based polymeric microsponges for the topical delivery of therapeutic agents has attracted the interest of pharmaceutical scientists around the globe in recent years. This work represents preparation, optimization (using Box–Behnken design [BBD]), and characterization (in-vitro and ex-vivo) of ethylcellulose microsponges loaded with vanillin for effective topical delivery to treat wounds. Vanillin-ethylcellulose microsponges were prepared by using quasi-emulsion solvent diffusion and optimized formulation (F9) (containing 100 mg ethylcellulose, 10 mL dichloromethane, 100 mg vanillin, and 90 mg polyvinyl alcohol) developed showed particle size (90.3 ± 2.9 µm), high entrapment of vanillin (79.0 ± 2.8%), and optimum colloidal properties (zeta potential = −37.91 ± 2.44 mV; polydispersity index (PDI) = 0.224 ± 0.23). Optimized formulation extended the release of vanillin (96.68 ± 3.11%) in-vitro for 24 h. Vanillin-ethylcellulose microsponges (F9) dispersed in Carbopol 940 gel showed limited ex-vivo skin permeation (steady-state flux, JSS = 243.7 ± 6.2 µg/cm2/h) and higher skin retention (82.46 ± 6.74%) for 24 h in pig ear skin compared to plain vanillin Carbopol 940 gel (steady-state flux, JSS = 1350 ± 10.8 µg/cm2/h, skin retention = 33.66 ± 4.53%). Results of confocal laser scanning microscopy (CLSM) of Vanillin-ethylcellulose microsponges (F9) Carbopol 940 gel revealed accumulation of microsponges in the stratum corneum layer of skin as a depot. Microsponges-based Carbopol 940 gel also displayed excellent in-vitro antibacterial activity (zone of inhibition = 24.2 ± 1.3 mm) against Staphylococcus aureus for 24 h compared to plain vanillin Carbopol 940 gel (zone of inhibition = 10.30 ± 1.2 mm) that was considered good for its wound healing activity. Therefore, developed vanillin-loaded ethylcellulose microsponges could be effectively used in the treatment of wounds by reducing side effects associated with vanillin and promoting its localized delivery in Carbopol 940 gel form.