Ghosh Santanu, Kar Nabanita, Bera Tanmoy
Laboratory of Nanomedicine, Division of Pharmaceutical Biotech., Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700 032, West Bengal, India.
Laboratory of Nanomedicine, Division of Pharmaceutical Biotech., Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700 032, West Bengal, India.
Int J Biol Macromol. 2016 Dec;93(Pt A):961-970. doi: 10.1016/j.ijbiomac.2016.09.014. Epub 2016 Sep 17.
Oleanolic acid (OA) has low aqueous solubility and low permeability, which results poor bioavailability. To surmount the inadequacy, our aim was to fabricate oleanolic acid loaded poly lactic co- glycolic acid (PLGA)- d-α- tocopheryl polyethylene glycol 1000 succinate (TPGS) nanoparticles, which could be efficacious for the treatment of Leishmania donovani mediated visceral leishmaniasis (VL). OA loaded PLGA- TPGS nanoparticles were prepared by emulsion solvent evaporation technique. Cellular uptake was investigated. In vitro cumulative drug release study was carried out. In vitro susceptibility was confirmed against the amastigotes of Leishmania donovani AG83 wild and drug resistant strains. In vivo antileishmanial activity was evaluated against wild type amastigotes of L. donovani. OA loaded nanoparticles were successfully formulated. The highest drug loading was found to be 11.08%±0.35%. 85.66%±0.56% was the highest in vitro OA release for 30days among the formulations. In vivo study revealed that, 98.82±1.92% amastigote burden in spleen of BALB/c mice were suppressed by the polymeric nanoformulation of OA. Experimental OA nanoparticle formulation proved itself as an attractive carrier for OA which was significantly efficacious against both in vitro and in vivo amastigote form of Leishmania donovani than pure OA for chemotherapeutic intervention of visceral leishmaniasis.
齐墩果酸(OA)的水溶性和渗透性较低,导致其生物利用度较差。为克服这一不足,我们的目标是制备负载齐墩果酸的聚乳酸-乙醇酸共聚物(PLGA)-d-α-生育酚聚乙二醇1000琥珀酸酯(TPGS)纳米颗粒,其可有效治疗杜氏利什曼原虫介导的内脏利什曼病(VL)。通过乳液溶剂蒸发技术制备了负载OA的PLGA-TPGS纳米颗粒。研究了细胞摄取情况。进行了体外药物累积释放研究。证实了对杜氏利什曼原虫AG83野生株和耐药株无鞭毛体的体外敏感性。评估了对杜氏利什曼原虫野生型无鞭毛体的体内抗利什曼活性。成功制备了负载OA的纳米颗粒。发现最高载药量为11.08%±0.35%。在各制剂中,30天的最高体外OA释放率为85.66%±0.56%。体内研究表明,OA的聚合物纳米制剂可抑制BALB/c小鼠脾脏中98.82±1.92%的无鞭毛体负荷。实验性OA纳米颗粒制剂证明自身是一种有吸引力的OA载体,对于内脏利什曼病的化疗干预,其对杜氏利什曼原虫的体外和体内无鞭毛体形式均比纯OA具有显著疗效。