Department of Pharmaceutical Biotechnology, Poona College of Pharmacy, Bharati Vidyapeeth University, Pune, India.
Curr Drug Deliv. 2012 Sep;9(5):477-86. doi: 10.2174/156720112802650653.
Lack of suitable formulations often obscures the potential of natural medicine. Moreover, the presence of myriad of constituents with varied physicochemical properties makes fabrication of stable phyto-formulation extremely difficult. Bee propolis is one such material that suffers inadequate clinical application, despite having diverse pharmacological activities, solely attributed to deficit of appropriate formulations. In this study, we have presented a possibility of fabricating liposomes as a platform nano-formulation for enhancement of hepatoprotective activity of propolis. Hepatoprotective efficacy of the propolis is limited by its poor oral absorption. Moreover, the exact composition of the propolis being yet undefined, indeed unconfined, it cannot be administered parenterally. In order to address the foregoing issue, propolis liposomes suitable for oral administration and having higher entrapment efficiency were formulated through a modified ethanol injection method. Effect of phospholipids (PL) and cholesterol (CH) concentration on the formulation characteristics was checked statistically by 3(2) factorial approach. Liposomes were characterized for vesicle diameter (Dv), entrapment efficiency (EE), zeta potential (ζ p), TEM and drug release kinetics. Clinical efficacy of the formulation was assessed using acetaminophen induced hepatotoxicity in rat model. Biochemical parameters such as AST, ALT, ALP and TBARS, as well as histopathological aspects were studied. Stable unilamellar vesicles were formed according to 3(2) factorial approach. Dv, EE and ζ p were ranging between 216 to 437 nm, 79.53 to 93.01% & -27.8 to -31.2 mV, respectively. Marked positive effect of PL and CH and propolis concentrations was seen on Dv as well as EE. Release of propolis in acidic media followed zero order kinetics while in alkaline media it followed 1(st) order kinetics. Formulation was able to suppress AST, ALT, ALP & TBARS levels in hepatotoxicity induced experimental animals and promote tissue healing, in a manner more effective than plain EEP as well as silymarin. In conclusion, suitability of liposomes as a fundamental formulation for enhancing hepatoprotective activity of multi-component propolis was justified.
缺乏合适的制剂常常掩盖了天然药物的潜力。此外，由于存在多种具有不同物理化学性质的成分，使得稳定的植物制剂的制造变得极其困难。蜂胶就是这样一种材料，尽管具有多种药理活性，但由于缺乏合适的制剂，其临床应用仍然不足。在这项研究中，我们提出了一种可能性，即通过制备脂质体作为平台纳米制剂来提高蜂胶的保肝活性。蜂胶的保肝作用受到其口服吸收不良的限制。此外，由于蜂胶的确切成分尚未确定，实际上是不确定的，因此不能进行肠胃外给药。为了解决上述问题，我们通过改良的乙醇注入法制备了适合口服给药且具有更高包封效率的蜂胶脂质体。通过 3(2) 因子设计检查了磷脂 (PL) 和胆固醇 (CH) 浓度对制剂特性的影响。对脂质体的粒径 (Dv)、包封效率 (EE)、Zeta 电位 (ζ p)、TEM 和药物释放动力学进行了表征。通过在大鼠模型中用对乙酰氨基酚诱导肝毒性来评估制剂的临床疗效。研究了生化参数如 AST、ALT、ALP 和 TBARS，以及组织病理学方面。根据 3(2) 因子设计形成了稳定的单层囊泡。Dv、EE 和 ζ p 的范围分别为 216 至 437nm、79.53 至 93.01%和-27.8 至-31.2mV。PL 和 CH 以及蜂胶浓度对 Dv 和 EE 均有显著的正效应。在酸性介质中，蜂胶的释放遵循零级动力学，而在碱性介质中遵循一级动力学。制剂能够抑制肝毒性诱导的实验动物中 AST、ALT、ALP 和 TBARS 水平，并促进组织愈合，其效果优于普通 EEP 和水飞蓟素。总之，脂质体作为增强多组分蜂胶保肝活性的基本制剂是合理的。
