Maurya Lakshmi, Singh Sanjay, Rajamanickam Vijayakumar M, Narayan Gopeshwar
Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), Varanasi, U.P, India.
Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, U.P, India.
Curr Drug Deliv. 2018;15(8):1135-1145. doi: 10.2174/1567201815666180409105410.
Vinorelbine bitartrate (VRL), a semi synthetic vinca alkaloid approved for breast cancer, has been proven to be beneficial as first line and subsequent therapies. However, its hydrophilic and thermo labile nature provides hindrance to oral clinical translation.
The current work focused on the application of DOE a modern statistical optimization tool for the development and optimization of a solid lipid nanoparticle (SLN) formulation that can encapsulate hydrophilic and thermolabile Vinorelbine bitartrate (VRL) to a maximum extent without compromising integrity and anticancer activity of the drug.
SLNs were prepared by solvent diffusion technique employing Taguchi orthogonal array design with optimized formulation and process variables. The emulsifying nature and low melting point of glyceryl mono-oleate (GMO) were exploited to enhance entrapment and minimizing temperature associated degradation, respectively. Moreover, two types of surfactants, Vitamin E TPGS (TPGS) and Poloxamer-188 were utilized to obtain TPGS-VRL-SLNs and PL-VRL-SLNs, respectively. The SLNs were characterized for various physicochemical properties, in-vitro drug release kinetics and anticancer activity by MTT assay on MCF-7 cancer cell lines.
The SLNs were found to be spherical in shape with entrapment efficiency (EE) up to 58 %. Invitro release studies showed biphasic release pattern following Korsemeyer peppas model with fickian release kinetics. Results of MTT assay revealed that TPGS-VRL-SLNs and PL-VRL-SLNs were 39.5 and 18.5 fold more effective, respectively, compared to the pristine VRL.
DOE approach was successfully applied for the development of VRL-SLNs. Enhanced entrapment and anticancer efficacy of TPGS-VRL-SLN can be attributed to emulsifying nature of GMO and inherent cytotoxic nature of TPGS, respectively, which synergizes with VRL. Therefore, TPGS associated SLNs may be potential carrier in cancer chemotherapeutics.
酒石酸长春瑞滨（VRL）是一种已被批准用于乳腺癌治疗的半合成长春花生物碱，已被证明作为一线及后续治疗是有益的。然而，其亲水性和热不稳定的性质阻碍了其口服临床转化。
目前的工作集中于应用DOE（一种现代统计优化工具）来开发和优化一种固体脂质纳米粒（SLN）制剂，该制剂能够在不损害药物完整性和抗癌活性的前提下，最大程度地包封亲水性和热不稳定的酒石酸长春瑞滨（VRL）。
采用溶剂扩散技术，利用田口正交阵列设计制备SLN，优化制剂和工艺变量。分别利用单油酸甘油酯（GMO）的乳化性质和低熔点来提高包封率并将与温度相关的降解降至最低。此外，使用两种类型的表面活性剂，维生素E TPGS（TPGS）和泊洛沙姆-188，分别获得TPGS-VRL-SLN和PL-VRL-SLN。通过MTT法在MCF-7癌细胞系上对SLN的各种物理化学性质、体外药物释放动力学和抗癌活性进行表征。
发现SLN呈球形，包封率（EE）高达58%。体外释放研究表明，按照Korsemeyer peppas模型呈现双相释放模式，具有菲克扩散释放动力学。MTT法结果显示，与原始VRL相比，TPGS-VRL-SLN和PL-VRL-SLN的有效性分别高39.5倍和18.5倍。
DOE方法成功应用于VRL-SLN的开发。TPGS-VRL-SLN包封率和抗癌效果的提高可分别归因于GMO的乳化性质和TPGS固有的细胞毒性性质，它们与VRL协同作用。因此，TPGS相关的SLN可能是癌症化疗中的潜在载体。
