Bhadra Dipankar, Bhadra Sulekha, Jain N K
Dept. of Pharmaceutical Sciences, Dr. H.S. Gour University, Sagar (MP), India.
J Pharm Pharm Sci. 2005 Sep 2;8(3):467-82.
A newer polymeric amphiphilic micellar system was developed in the present study for solubilization and controlled delivery of an antimalarial drug, Artemether (ART). Methoxy polyethylene glycol (MPEG) 2000 and 5000 were used as hydrophilic terminal.
The hydrophobic di-Fluorene methoxycarbonyl-l-lysine (di-FMOC-L-lysine) was linked initially to the single reactive end of MPEG, and to the two amino groups of l-lysine by consecutive peptide linkages and deprotection upto 2.5 generations (G). Half-generations are diFMOC-lysine terminated systems and full-generations are deprotected l-lysine terminated systems. The half-generation (0.5 G, 1.5 G and 2.5 G) dendritic micelles of MPEG 2000 and 5000 were used to solubilize artemether. IR, NMR and Mass spectroscopy characterized the synthesis of these micellar systems. The CMC of the systems was determined. Then formulations made were characterized for solubility enhancement (i.e. drug loading) and drug-release profile.
There is considerable solubility enhancement of artemether upto three to fifteen times depending on concentration, generation and type of dendritic micelles used. The size and shape were studied using transmission electron microscopy. The stability of the micellar formulation was also determined by storing the micelles at various temperatures for a definite period of time followed by its successive dilutions. The dendritic carriers were found to form stable micelles at 10-30 microg/ml (lower CMCs) depending on generation and type of MPEG used. The formulations increased the stability of the drug and also prolonged the release of artemether upto 1-2 days in vitro.
From all the studies performed, it can be concluded that these micellar systems can be used for the safe and effective delivery of insoluble bioactive.
在本研究中开发了一种新型的聚合物两亲性胶束系统，用于抗疟药物蒿甲醚（ART）的增溶和控释。甲氧基聚乙二醇（MPEG）2000和5000用作亲水端基。
首先将疏水性的二芴甲氧羰基-L-赖氨酸（二-FMOC-L-赖氨酸）连接到MPEG的单反应端，并通过连续的肽键连接和脱保护，直至2.5代（G），连接到L-赖氨酸的两个氨基上。半代是二-FMOC-赖氨酸终止的系统，全代是脱保护的L-赖氨酸终止的系统。使用MPEG 2000和5000的半代（0.5 G、1.5 G和2.5 G）树枝状胶束来增溶蒿甲醚。通过红外光谱、核磁共振和质谱对这些胶束系统的合成进行了表征。测定了系统的临界胶束浓度（CMC）。然后对制备的制剂进行增溶特性（即载药量）和药物释放曲线的表征。
根据所用树枝状胶束的浓度、代数和类型，蒿甲醚的溶解度显著提高了三到十五倍。使用透射电子显微镜研究了其大小和形状。通过将胶束在不同温度下储存一定时间，然后进行连续稀释，也测定了胶束制剂的稳定性。发现树枝状载体在10 - 30微克/毫升（较低的CMC）时形成稳定的胶束，这取决于所用MPEG的代数和类型。这些制剂提高了药物的稳定性，并且在体外将蒿甲醚的释放延长至1 - 2天。
从所有进行的研究可以得出结论，这些胶束系统可用于安全有效地递送不溶性生物活性物质。
