Liposomal Formulation and Characterization of the Opioid Peptide Leucine Enkephalin
Liposomal Formulation and Characterization of the Opioid Peptide Leucine Enkephalin
复制标题
阿片肽亮氨酸脑啡肽的脂质体配方和表征
DOI：
10.1111/j.2042-7158.1997.tb00502.x
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
A. Banga
中科院分区：
文献类型：
--
作者：
G. Betageri;N. B. Vutla;A. Banga
本研究的目的是将阿片肽亮氨酸脑啡肽包封在不同脂质组成的脂质体中，并在粒径、稳定性和释放特性方面进行表征。采用薄膜水化法制备多层脂质体（MLV），然后通过0·1 μm聚碳酸酯膜正压挤出，得到所需大小的大单层脂质体（LUV）。使用离心法（MLV）和鱼精蛋白聚集法（LUV）估计包封。
通过添加硬脂胺用于正电荷和磷脂酰丝氨酸用于负电荷，在脂质体表面上诱导电荷。研究了电荷、脂质组成和亮氨酸脑啡肽浓度对脂质体包封量的影响。还研究了电荷对脂质体制剂稳定性的影响。对脂质体制剂的粒度进行了表征，并研究了所有三种脂质体制剂在各种条件下的稳定性。
亮氨酸脑啡肽在LUVs中的包封受到脂质浓度、脂肪酸链长度、表面电荷和胆固醇添加的影响。包封率也随着药物浓度的增加而增加，最高可达1 mg mL −1。稳定性研究表明，在各种强制降解条件下，带有表面电荷的脂质体的聚集最小化。
药物从带正电荷的脂质体中的释放显著低于中性和带负电荷的脂质体，表明药物与脂质体之间存在静电相互作用。通过选择合适的脂质组成和药物浓度，可以获得最佳的包封率、稳定性和释放特性。
The objective of this study was to encapsulate opioid peptide leucine enkephalin in liposomes of various lipid composition, and characterize in terms of particle size, stability and release characteristics. Multilamellar liposomes (MLV) were prepared by a thin-film hydration method and subsequently converted to the desired sized large unilamellar liposomes (LUV) by extruding through 0·1 μm polycarbonate membrane using positive pressure. The encapsulation was estimated using centrifugation for MLVs and protamine aggregation method for LUVs.
Charge was induced on the liposome surface by adding stearylamine for positive charge and phosphotidylserine for negative charge. Effect of charge, lipid composition, and leucine enkephalin concentration on the amount of encapsulation in liposomes was studied. Effect of charge on the stability of liposome formulations was also investigated. Particle size of liposome preparations was characterized and stability of all three liposome formulations under various conditions was investigated.
Encapsulation of leucine enkephalin in LUVs was influenced by the lipid concentration, fatty acid chain length, surface charge and addition of cholesterol. The encapsulation also increased as a function of drug concentration up to 1 mg mL −1. Stability studies indicated that aggregation of liposomes was minimized with liposomes bearing surface charge under various stress conditions.
The release of drug from positively charged liposomes was significantly lower compared with neutral and negatively charged liposomes, indicating electrostatic interaction between the drug and liposome. It can be concluded that optimum encapsulation, stability and release characteristic can be achieved by choosing appropriate lipid composition and drug concentration.