Bhardwaj Ankur, Grobler Anne, Rath Goutam, Goyal Amit Kumar, Jain Amit Kumar, Mehta Abhinav
IIPC Lab, ISF College of Pharmacy, Ferozepur GT Road, Ghal Kalan, Moga-142001, Punjab, India.
Curr Drug Deliv. 2016;13(6):909-22. doi: 10.2174/1567201813666151231093605.
Mycobacterium tuberculosis (M. TB) remains the prime cause of bacterial mortality and morbidity world-wide. Therefore, effective delivery and targeting of drug to the cellular tropics is essentially required to generate significant results for tuberculosis treatment. The aim of the present study was to develop and characterize ligand anchored pH sensitive liposomes (TPSL) as dry powder inhaler for the targeted delivery of drugs in the target site i.e. lungs.
Ligand anchored PSL (TPSL) was prepared by thin film hydration for the combined delivery of Isoniazid (INH) and Ciprofloxacin HCl (CIP HCl) using 4-aminophenyl-α-D mannopyranoside (Man) as surface functionalized ligand and characterized using different parameters.
It was observed that size of the ligand anchored liposomes (TPSL) was slightly more than the non-ligand anchored liposomes (PSL). Drug release was studied at different pH for 24 hrs and it was observed that liposomes exhibited slow release at alkaline pH (58-64%) as compared to macrophage pH (81-87%) where it increased dramatically due to the destabilization of pH sensitive liposome (PSL). In vitro cellular uptake study showed that much higher concentration was achieved in the alveolar macrophage using ligand anchored liposomes as compared to its counterpart. In vivo study showed that maximum drug accumulation was achieved in the lung by delivering drug using ligand anchored PSL as compared to conventional PSL.
It was concluded that ligand anchored pH sensitive liposome is one of the promising systems for the targeted drug therapy in pulmonary tuberculosis.
结核分枝杆菌仍然是全球细菌性死亡和发病的主要原因。因此，为了在结核病治疗中取得显著效果，必须有效地将药物输送并靶向到细胞嗜性部位。本研究的目的是开发并表征配体锚定的pH敏感脂质体（TPSL）作为干粉吸入器，用于将药物靶向递送至靶部位即肺部。
采用薄膜水化法制备配体锚定的PSL（TPSL），以4-氨基苯基-α-D-甘露吡喃糖苷（Man）作为表面功能化配体，用于联合递送异烟肼（INH）和盐酸环丙沙星（CIP HCl），并使用不同参数对其进行表征。
观察到配体锚定脂质体（TPSL）的尺寸略大于非配体锚定脂质体（PSL）。在不同pH下研究了24小时的药物释放情况，发现脂质体在碱性pH下表现出缓慢释放（58 - 64%），而在巨噬细胞pH下（87 - 81%）释放量显著增加，这是由于pH敏感脂质体（PSL）的不稳定所致。体外细胞摄取研究表明，与非配体锚定脂质体相比，使用配体锚定脂质体在肺泡巨噬细胞中实现了更高的浓度。体内研究表明，与传统PSL相比，使用配体锚定的PSL递送药物时，肺部实现了最大的药物积累。
得出结论，配体锚定的pH敏感脂质体是肺结核靶向药物治疗的有前景的系统之一。
