Yingsukwattana Koson, Puttipipatkhachorn Satit, Ruktanonchai Uracha, Sarisuta Narong
a Department of Manufacturing Pharmacy, Faculty of Pharmacy , Mahidol University , Bangkok , Thailand .
b National Nanotechnology Center, National Science and Technology Development Agency , Pathumthani , Thailand , and.
J Liposome Res. 2016;26(1):69-79. doi: 10.3109/08982104.2015.1039030. Epub 2015 May 6.
Oral delivery of peptide and protein drugs still remains the area of challenges due to their low stability and permeability across GI tract. Among numerous attempts, the receptor-mediated drug targeting is a promising approach to enhance GI permeability.
The aim of this study was to prepare mannosylated buserelin acetate (MANS-BA) proliposome powders grafted with N-octadecyl-d-mannopyranosylamine (SAMAN) as targeting moiety and evaluate their permeability across Caco-2 cell monolayers.
The MANS-BA proliposome powders were prepared by coprecipitation method. The targeting moiety SAMAN was synthesized in-house and confirmed by characterization using Fourier transform infrared (FTIR) and differential scanning calorimeter (DSC).
The MANS-BA liposomes reconstituted from proliposome powders exhibited the oligolamellar vesicular structure of phospholipid bilayer. Their size, zeta potential and entrapment efficiency were in the ranges of 93.11-218.95 nm, -24.03 to -37.15 mV and 21.12-33.80%, respectively. The permeability of reconstituted MANS-BA liposomes across Caco-2 cell monolayers was significantly enhanced to about 1.2- and 2.2-fold over those of conventional BA liposomes and solution, respectively.
Increase in dicetylphosphate, cholesterol and SAMAN contents resulted in significant increase in size and zeta potential of reconstituted MAN-BA liposomes. The entrapment efficiency was increased with increasing dicetylphosphate and mannitol contents in liposomes containing cholesterol.
The significantly enhanced permeability across Caco-2 cell monolayers of MANS-BA liposomes might be due to the role of mannose receptor on intestinal enterocytes.
肽类和蛋白质药物的口服给药仍然是一个具有挑战性的领域，因为它们在胃肠道中的稳定性和渗透性较低。在众多尝试中，受体介导的药物靶向是一种增强胃肠道渗透性的有前途的方法。
本研究的目的是制备接枝有N-十八烷基-D-甘露糖胺（SAMAN）作为靶向部分的甘露糖基化醋酸布舍瑞林（MANS-BA）前体脂质体粉末，并评估它们对Caco-2细胞单层的渗透性。
通过共沉淀法制备MANS-BA前体脂质体粉末。靶向部分SAMAN在内部合成，并通过傅里叶变换红外光谱（FTIR）和差示扫描量热仪（DSC）表征进行确认。
由前体脂质体粉末重构的MANS-BA脂质体呈现出磷脂双层的寡层囊泡结构。它们的大小、ζ电位和包封率分别在93.11 - 218.95nm、-24.03至-37.15mV和21.12 - 33.80%范围内。重构的MANS-BA脂质体对Caco-2细胞单层的渗透性分别比传统BA脂质体和溶液显著提高了约1.2倍和2.2倍。
磷酸二鲸蜡酯、胆固醇和SAMAN含量的增加导致重构的MAN-BA脂质体的大小和ζ电位显著增加。在含有胆固醇的脂质体中，随着磷酸二鲸蜡酯和甘露醇含量的增加，包封率增加。
MANS-BA脂质体对Caco-2细胞单层的渗透性显著增强可能归因于肠道肠细胞上甘露糖受体的作用。
