Synthesis of Sulfated Cyclodextrin Amphiphiles with Liposomal Encapsulation Properties

Tetsuya Furuike,Hiroshi Tamura,Koichi Nasu

doi:10.4236/jeas.2015.53012

Abstract

A novel class of amphiphiles with sulfate groups at the C-6 position and palmitoyl groups at the C-2, 3 positions of α-, β-, and γ-cyclodextrin (CD) were efficiently synthesized. These compounds formed stable monolayers with high collapse pressures at the air-water interface. The mixed monolayer behaviors of the 6-O-sulfated CD amphiphiles (SO3-CDC16) in the presence of dipalmitoyl phosphatidylcholine (DPPC) and cholesterol were discussed using the surface pressure-molecular area (π-A) isotherms. The collapse pressures showed maxima at molar ratios of SO3-CDC16 lower than 10 mol%. A morphological analysis of the liposomes containing DPPC and 4 mol% SO3-CDC16 formed in PBS was carried out using transmission electron microscopy with negative staining, and vesicles with maximum diameters of 350-500 nm were observed. Moreover, the releasing ability of these liposomes was examined using a fluorescent compound, calcein. It was clearly shown that liposomes containing SO3-CDC16 could release encapsulated calcein more easily than liposomes consisting only of DPPC, and that the release rate depended on the phase transition temperature of the SO3-CDC16 included in the liposome membrane.

Highlights

IntroductionThe surface pressure-molecular area (π-A) isotherms of the monolayers disclose the size of the molecules, as well as the stability and phase behaviors of the monolayer films
We reported the synthesis of 6-O-sulfated CD amphiphiles (SO3-CDC16) and preliminary data on the formation of liposomes containing these CD derivatives [34]
The obtained amphiphiles formed stable monolayers in the presence of dipalmitoyl phosphatidylcholine (DPPC) and cholesterol at the air-water interface, and the collapse pressures were maximized at molar ratios of SO3-CDC16 lower than 10 mol%

Summary

Introduction

The surface pressure-molecular area (π-A) isotherms of the monolayers disclose the size of the molecules, as well as the stability and phase behaviors of the monolayer films. The miscibility of mixed monolayers composed of two lipids with various concentration ratios can be elucidated from the π-A isotherms. Liposomes are artificial cell-like materials and have been considered as a strong candidate for a drug delivery carrier [29][33]. We reported the synthesis of 6-O-sulfated CD amphiphiles (SO3-CDC16) and preliminary data on the formation of liposomes containing these CD derivatives [34]. The miscibility of monolayers composed of SO3-CDC16 with dipalmitoyl phosphatidylcholine (DPPC) and cholesterol was investigated in detail. To test the encapsulation ability of the liposomes, 3,3’-bis [N,N-bis(carboxymethyl) aminomethyl]fluoroscein (calcein), an anionic dye was captured in the liposomes and changes in fluorescence intensity were used to monitor the time dependence of dye leakage

Methods

Results

Conclusion