Pradhan Madhulika, Singh Deependra, Singh Manju Rawat
University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur, Chhattisgarh, 492010, India.
University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur, Chhattisgarh, 492010, India.
Chem Phys Lipids. 2015 Feb;186:9-16. doi: 10.1016/j.chemphyslip.2014.11.004. Epub 2014 Nov 20.
The aim of this study was to develop, optimize and evaluate the potential of solid lipid nanoparticles (SLNs) as a topical delivery system for targeted and prolonged release of Fluocinolone acetonide (FA). FA loaded SLNs were successfully developed by an emulsification-ultrasonication method and optimized using 17-run, 3-factor, 3-level Box-Behnken design of Design Expert software. SLNs were evaluated for particle size, polydispersity index, zeta potential, drug encapsulation efficiency and drug loading. Shape and surface morphology of the SLNs confirmed spherical shape of nanoparticles when investigated under a transmission electron microscope. Complete encapsulation of drug in the nanoparticles was confirmed by powder X-ray diffraction and differential scanning calorimetry. The drug release study confirmed prolonged release from the SLNs following Higuchi release kinetics with R(2) value of 0.995 where as pure drug suspension exhibited faster drug release following zero order release kinetics with R(2) value of 0.992. Stability study confirmed that SLNs were stable for 3 months at 4 °C. Furthermore, in vitro skin distribution studies showed presence of significant amount of FA on the epidermal layer of skin when treated with FA loaded SLNs suspension while plain FA suspension showed minimum amount of FA in the epidermis and dermis. Moreover, selective accumulation of FA in the epidermis might eliminate adverse side effects associated with systemic exposure. Results demonstrated that FA loaded SLNs could be a promising modality for psoriasis treatment but to establish clinical utility of the present system further studies are required in clinically relevant models.
本研究的目的是开发、优化并评估固体脂质纳米粒（SLNs）作为醋酸氟轻松（FA）靶向和长效释放的局部给药系统的潜力。通过乳化超声法成功制备了负载FA的SLNs，并使用Design Expert软件的17次运行、三因素、三水平Box-Behnken设计进行优化。对SLNs的粒径、多分散指数、zeta电位、药物包封率和载药量进行了评估。在透射电子显微镜下观察时，SLNs的形状和表面形态证实了纳米粒呈球形。粉末X射线衍射和差示扫描量热法证实药物完全包裹在纳米粒中。药物释放研究证实，SLNs符合Higuchi释放动力学，呈现长效释放，R(2)值为0.995，而纯药物混悬液符合零级释放动力学，药物释放较快，R(2)值为0.992。稳定性研究证实，SLNs在4℃下可稳定3个月。此外，体外皮肤分布研究表明，用负载FA的SLNs混悬液处理皮肤时，表皮层存在大量FA，而普通FA混悬液在表皮和真皮中的FA含量最低。此外，FA在表皮中的选择性蓄积可能消除与全身暴露相关的不良副作用。结果表明，负载FA的SLNs可能是治疗银屑病的一种有前景的方式，但要确定本系统的临床实用性，还需要在临床相关模型中进行进一步研究。
