TIFAC Centre of Relevance and Excellence in NDDS, Pharmacy Department, Faculty of Technology & Engineering, The M.S. University of Baroda, Vadodara, India.
TIFAC Centre of Relevance and Excellence in NDDS, Pharmacy Department, Faculty of Technology & Engineering, The M.S. University of Baroda, Vadodara, India; Tatyasaheb Kore College of Pharmacy, Warananagar, Tal: Panhala, Dist: Kolhapur, Maharashtra, India.
Int J Biol Macromol. 2019 Feb 1;122:367-379. doi: 10.1016/j.ijbiomac.2018.10.071. Epub 2018 Oct 17.
Acylated chitosan (Myristoyl and Octanoyl) coated paclitaxel-loaded liposomal formulation was developed with an aim to overcome the cremophor EL related toxicities. They were evaluated for drug entrapment, in vitro drug release, and cytotoxicity and cell uptake behavior using A549 cells. The Tc radio-labeled formulations were also evaluated in vivo in Ehrlich Ascites Tumor (EAT) bearing mice for biodistribution and tumor uptake. The mean particle size of both coated and uncoated liposomal formulations was found to be in the range of 180-200 nm with high drug entrapment efficiency (>90% in case of uncoated liposomes and 80 ± 5% in case of coated liposomes). The uncoated liposomes displayed negative zeta potential (-10.5 ± 4.9 mV) whereas coated liposomes displayed positive zeta potential in the range of +21 to +27 mV. Slower drug release was observed in case of liposomes coated with acylated chitosans as compared to uncoated and native chitosan coated liposomes. All liposomal formulations were found less cytotoxic than paclitaxel injection (Celtax™, Celon Labs, India). In vitro cell uptake and intracellular distribution studies confirmed the cytosolic delivery of uncoated and coated liposomes. The myristoyl chitosan coated liposomal system (LMC) exhibited improved pharmacokinetic, biodistribution and tumor uptake characteristics over other formulations. These obtained results confirmed the potential application of acylated chitosn coated liposomal delivery systems (LMC) in tumor targeting of paclitaxel and other drugs.
酰化壳聚糖（肉豆蔻酰和辛酰）包裹的紫杉醇载脂质体制剂的开发旨在克服聚氧乙烯蓖麻油相关的毒性。通过 A549 细胞评估了它们的药物包封率、体外药物释放、细胞毒性和细胞摄取行为。Tc 放射性标记的制剂也在荷 Ehrlich 腹水瘤（EAT）的小鼠体内进行了生物分布和肿瘤摄取评估。发现包裹和未包裹脂质体制剂的平均粒径均在 180-200nm 范围内，具有较高的药物包封效率（未包裹脂质体为>90%，包裹脂质体为 80±5%）。未包裹的脂质体显示出负的 ζ 电位（-10.5±4.9mV），而包裹的脂质体显示出正的 ζ 电位，范围在+21 到+27mV。与未包裹和天然壳聚糖包裹的脂质体相比，用酰化壳聚糖包裹的脂质体显示出较慢的药物释放。所有脂质体制剂的细胞毒性均低于紫杉醇注射液（Celtax™，Celon Labs，印度）。体外细胞摄取和细胞内分布研究证实了未包裹和包裹脂质体的细胞质递送。与其他制剂相比，肉豆蔻酰壳聚糖包裹的脂质体系统（LMC）表现出改善的药代动力学、生物分布和肿瘤摄取特性。这些结果证实了酰化壳聚糖包裹的脂质体给药系统（LMC）在紫杉醇和其他药物的肿瘤靶向中的潜在应用。
