Pharmaceutics and Pharmacokinetics Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, UP, 226031, India.
Parasitology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, UP, 226031, India.
Pharm Res. 2018 Feb 9;35(3):60. doi: 10.1007/s11095-017-2293-1.
To fabricate, characterize and evaluate 3-O-sn-Phosphatidyl-L-serine (PhoS) anchored PLGA nanoparticles for macrophage targeted therapeutic intervention of VL.
PLGA-AmpB NPs were prepared by well-established nanoprecipitation method and decorated with Phos by thin film hydration method. Physico-chemical characterization of the formulation was done by Zetasizer nano ZS and atomic force microscopy.
The optimized formulation (particle size, 157.3 ± 4.64 nm; zeta potential, - 42.51 ± 2.11 mV; encapsulation efficiency, ∼98%) showed initial rapid release up to 8 h followed by sustained release until 72 h. PhoS generated 'eat-me' signal driven augmented macrophage uptake, significant increase in in-vitro (with ∼82% parasite inhibition) and in-vivo antileishmanial activity with preferential accumulation in macrophage rich organs liver and spleen were found. Excellent hemo-compatibility justified safety profile of developed formulation in comparison to commercial formulations.
The developed PhoS-PLGA-AmpB NPs have improved efficacy, and necessary stability which promisingly put itself as a better alternative to available commercial formulations for optimized treatment of VL.
制备、表征和评价 3-O- sn -磷酰丝氨酸（PhoS）锚定的 PLGA 纳米粒，用于巨噬细胞靶向治疗 VL。
采用已建立的纳米沉淀法制备 PLGA-ampB NPs，并通过薄膜水化法用 Phos 进行修饰。通过 Zetasizer nano ZS 和原子力显微镜对制剂进行理化特性表征。
优化的配方（粒径 157.3 ± 4.64nm；zeta 电位-42.51 ± 2.11mV；包封效率约 98%）表现出初始快速释放，持续至 72h。PhoS 产生“吃我”信号，驱动巨噬细胞摄取增加，在体外（具有约 82%的寄生虫抑制作用）和体内抗利什曼原虫活性显著增加，在富含巨噬细胞的肝脏和脾脏等器官中优先积累。与商业制剂相比，良好的血液相容性证明了所开发制剂的安全性。
所开发的 PhoS-PLGA-ampB NPs 提高了疗效和必要的稳定性，有望成为现有商业制剂的更好替代品，用于优化 VL 的治疗。
