Development and optimization of cilostazol loaded transethosomal gel for improved performance.

Abstract

Deep vein thrombosis (DVT) is the third major leading cause of mortality and morbidity after cardiovascular disease and stroke. Cilostazol (CLZ) being one of the antiplatelet agents is effectively used in DVT. However, its oral administration is associated with several problems, such as gastrointestinal side effects and extensive first-pass metabolism. Herein, CLZ-loaded transethosomes (CLZ-TEs) were prepared and incorporated in chitosan gel (CLZ-TEG) for transdermal administration. Box-Behnken Design Expert^® software was used to statistically optimize CLZ-TEs. Particle properties, Transmission electron microscopy (TEM), and Fourier Transform Infrared spectroscopy (FTIR) analyses of CLZ-TEs were accomplished followed by in vitro release and permeation studies and its comparison with CLZ-TEG, CLZ-dispersion (Ds) and CLZ-G. Moreover, skin irritation and pharmacokinetics studies of the optimized CLZ-TEG were executed. The optimized CLZ-TEs showed a mean particle size of 174 nm, polydispersity index of 0.173, zeta potential of -30 mV, and entrapment efficiency of 99%. TEM exhibited spherical nanovesicles and FTIR demonstrated compatibility of the excipients. Moreover, CLZ-TEG was homogeneous, smooth, and spreadable. Similarly, CLZ-TEG displayed sustained release and enhanced permeation of the CLZ. Furthermore, pharmacokinetic study showed significantly improved (p < 0.05) bioavailability of CLZ-TEG when compared with CLZ-G and CLZ-Ds. It was concluded that CLZ-TEG may be a potential candidate for the management of DVT.