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载顺铂脂质-壳聚糖杂化纳米粒的控释

Lipid-chitosan hybrid nanoparticles for controlled delivery of cisplatin.

机构信息

a Center of Pharmaceutical Biotechnology and Nanomedicines, Northeastern University , Boston , MA , USA.

b Department of Pharmacy, The Islamia University of Bahawalpur , Bahawalpur , Pakistan.

出版信息

Drug Deliv. 2019 Dec;26(1):765-772. doi: 10.1080/10717544.2019.1642420.

Abstract

Lipid-polymer hybrid nanoparticles (LPHNP) are delivery systems for controlled drug delivery at tumor sites. The superior biocompatible properties of lipids and structural advantages of polymers can be obtained using this system for controlled drug delivery. In this study, cisplatin-loaded lipid-chitosan hybrid nanoparticles were formulated by the single step ionic gelation method based on ionic interaction of positively charged chitosan and negatively charged lipid. Formulations with various chitosan to lipid ratios were investigated to obtain the optimal particle size, encapsulation efficiency, and controlled release pattern. Transmission electron microscope and dynamic light scattering analysis demonstrated a size range of 181-245 nm and a zeta potential range of 20-30 mV. The stability of the formulation was demonstrated by thermal studies. Cytotoxicity and cellular interaction of cisplatin-loaded LPHNP were investigated using cell-based assays using the A2780 ovarian carcinoma cell line. The pharmacokinetics study in rabbits supported a controlled delivery of cisplatin with enhanced mean residence time and half-life. These studies suggest that cisplatin loaded LPHNP have promise as a platform for controlled delivery of cisplatin in cancer therapy.

摘要

脂质-聚合物杂化纳米颗粒(LPHNP)是用于肿瘤部位药物控制释放的递药系统。通过该系统进行药物控制释放,可以获得脂质的优异生物相容性和聚合物的结构优势。在本研究中,通过基于带正电荷壳聚糖与带负电荷脂质之间的离子相互作用的单步离子凝胶化方法,制备了载顺铂的脂质-壳聚糖杂化纳米颗粒。考察了不同壳聚糖与脂质比例的配方,以获得最佳的粒径、包封效率和控制释放模式。透射电子显微镜和动态光散射分析表明粒径范围为 181-245nm,Zeta 电位范围为 20-30mV。通过热研究证明了配方的稳定性。使用基于细胞的测定法,使用 A2780 卵巢癌细胞系,研究了载顺铂的 LPHNP 的细胞毒性和细胞相互作用。在兔体内的药代动力学研究表明,载顺铂的 LPHNP 具有增强的平均驻留时间和半衰期,可实现顺铂的控制释放。这些研究表明,载顺铂的 LPHNP 有望成为癌症治疗中顺铂控制释放的平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a2b/6711028/127d64b3d015/IDRD_A_1642420_F0001_B.jpg

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