Original Article
Cholesterol succinyl chitosan anchored liposomes: preparation, characterization, physical stability, and drug release behavior

https://doi.org/10.1016/j.nano.2009.09.005Get rights and content

Abstract

The purpose of this study was to prepare cholesterol succinyl chitosan anchored liposomes (CALs) and to investigate their characterization, physical stability, and drug release behavior in vitro. Three cholesterol succinyl chitosan (CHCS) conjugates with different substitution degrees (DS) of the cholesterol moiety were synthesized and used as the anchoring materials to coating on the liposome surface by the incubation method. CALs were almost spherical and had a classic shell-core structure. Compared with plain liposomes and chitosan-coated liposomes (CCLs), CALs had larger sizes, higher zeta potentials, and better physical stability after storage at 4 ± 2°C and 25 ± 2°C. Epirubicin, as a model drug, was effectively loaded into CALs and exhibited the more sustained release in both phosphate buffer solution (pH 7.4) and 1% (vol/vol) aqueous fetal bovine serum compared to plain liposomes and CCLs.

From the Clinical Editor

Cholesterol succinyl chitosan anchored liposomes (CAL) as delivery vehicles are characterized in this work, including their physical stability and drug release behavior in vitro. Epirubicin as a model drug, was effectively loaded into CALs, and exhibited sustained release behavior both in phosphate buffer solution (PBS, pH 7.4) and 1% (V/V) aqueous fetal bovine serum (FBS).

Section snippets

Materials

Biomedical grade chitosan (deacetylation degree was 92%, viscosity average molecular weight was 8.0 × 104 Da) was supplied by Yuhuan Ocean Biochemical Co., Ltd. (Zhejiang, China). Three CHCS conjugates were synthesized by the method that we previously reported.14 The substitution degrees (DS) of the cholesterol moiety of CHCS, defined as the amount of cholesterol moieties per 100 glucosamine units of chitosan, was determined by the colloid titration method,15 and the DS values of three CHCS

Preparation and characterization of CALs

In our study, the different polysaccharide/lipid weight ratios were investigated to prepare CAL. Figure 1 shows the effects of polysaccharide/lipid weight ratio on the size (Figure 1, A) and the zeta potential (Figure 1, B) of CAL, and the same trend occurred among CALs with different DS of the cholesterol moiety. Compared with the plain liposomes (size 148.2 ± 3.0 nm and zeta potential −4.75 mV), CALs had significantly larger sizes and positive zeta potentials, which indicated that CHCS

Discussion

Recently, many investigations into CCL have been performed to enhance the stability of liposomes and increase their intestinal uptake.22, 23, 24 We previously hoped to use CCL as the carrier of anticancer drugs, but the chitosan layer formed by the electrostatic attractive interaction between the positively charged amino groups in chitosan molecules and the negatively charged surface of liposomes was not effective enough to significantly stabilize liposomes in vitro, so that the anchoring

Acknowledgment

The authors thank Drs. Xindu Yang, Wenzhi Yang, and Hongli Chen for their helpful discussion and suggestions.

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    This work was supported by the National Natural Science Foundation of China (grant no. 30900303).

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