Rehman Midhat, Sohail Saba, Ali Zakir, Alamri Ali H, Lahiq Ahmed A, Alqahtani Taha, Alyahya Saleh, Din Fakhar Ud
Nanomedicine Research Group, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
Pharm Dev Technol. 2025 Jul;30(6):821-839. doi: 10.1080/10837450.2025.2521055. Epub 2025 Jun 24.
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 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 ( < 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.
深静脉血栓形成（DVT）是仅次于心血管疾病和中风的第三大主要致死和致病原因。西洛他唑（CLZ）作为抗血小板药物之一，在DVT治疗中得到有效应用。然而，其口服给药存在一些问题，如胃肠道副作用和广泛的首过代谢。在此，制备了负载西洛他唑的传递体（CLZ-TEs），并将其掺入壳聚糖凝胶（CLZ-TEG）中用于透皮给药。使用Box-Behnken Design Expert软件对CLZ-TEs进行统计学优化。完成了CLZ-TEs的颗粒特性、透射电子显微镜（TEM）和傅里叶变换红外光谱（FTIR）分析，随后进行释放和渗透研究，并将其与CLZ-TEG、CLZ分散体（Ds）和CLZ-G进行比较。此外，还进行了优化后的CLZ-TEG的皮肤刺激性和药代动力学研究。优化后的CLZ-TEs平均粒径为174 nm，多分散指数为0.173，zeta电位为-30 mV，包封率为99%。TEM显示为球形纳米囊泡，FTIR证明了辅料的相容性。此外，CLZ-TEG均匀、光滑且易于涂抹。同样，CLZ-TEG显示出西洛他唑的缓释和渗透增强。此外，药代动力学研究表明，与CLZ-G和CLZ-Ds相比，CLZ-TEG的生物利用度显著提高（<0.05）。得出结论，CLZ-TEG可能是治疗DVT的潜在候选药物。
