Preparation and properties of poly(vinyl alcohol)-stabilized liposomes

doi:10.1016/j.ijpharm.2006.03.016

International Journal of Pharmaceutics

Volume 318, Issues 1–2, 2 August 2006, Pages 55-61

https://doi.org/10.1016/j.ijpharm.2006.03.016 Get rights and content

Abstract

The purpose of this work is to evaluate the improvement in physical stability of poly(vinyl alcohol) (PVA) modified liposomes. Liposomes composed of soya phosphatidylcholile (SPC) and cholesterol (1:1 molar ratio) were prepared by reverse phase evaporation method. Two types of interaction between liposome and PVA were investigated: PVA addition into lipid bilayer during liposome preparation and coating of already formed liposomes with PVA. The microparticles system was morphologically characterized by transmission electron microscopy (TEM) and particles analysis. Changes in particles size and zeta potential confirmed the existence of a thick polymer layer on the surface of liposomes. The amount of PVA adsorbing to liposomes and the encapsulation efficiency increased with increasing polymer concentration. The physical stability was evaluated by measuring the release rate of contents at 20 and 37 °C, the PVA modified liposomes were more stable than the conventional liposomes. Comparing with PVA-coated liposomes, the liposomes with PVA addition to the bilayer were more stable, and had higher entrapment efficiency.

Introduction

Liposomes have been first described by Bangham (Bangham et al., 1965). Due to their biocompatibility and capability of incorporating both hydrophilic and lipophilic drugs, liposomes have been investigated as effective drug carrier (Gregoriadis, 1995, Amamath and Umas, 1997, Lasic and Papahadjopoulos, 1996, Lasic, 1998).

However, the limited stability of liposomes during storage and administration restricts their application and development (in vitro and in vivo). Many attempts have been made to enhance the stability of liposomes. The initial research showed dramatically improved stability of liposomes composed of cholesterol and neutral long chain saturated phospholipids (Kerby et al., 1980). However, the modification of bilayer composition alone is not sufficient to get stable liposomes. Successful results were obtained by the modification of liposome with several substances, such as, poly(ethylene glycol) (PEG) (Klibanov et al., 1990, Allen et al., 1991, Lebanon et al., 1990) poloxamer (Jamshaid et al., 1988), polysorbate 80 (Kronberg et al., 1990, Jorg, 2001), carboxymethyl chitin (Dong and Rogers, 1991), chitosan (Guo et al., 2003, Rengel and Barisic, 2002) and dextran derivatives (Elferink et al., 1992) have been used for preparation of polymer-coated liposomes.

Apart from these polymers, Poly(vinyl alcohol) (PVA) and PVA-R are also used to improve liposomal physical stability (Takeuchi et al., 1998, Takeuchi et al., 1999, Takeuchi et al., 2000), which was made by simply mixing the liposomal suspension with the polymer solution.

In this study, liposomes were modified with PVA in two different methods, the morphological property of liposome were investigated with transmission electron microscopy (TEM). Properties of coatings were evaluated by measuring the particle size and zeta potential. The physical stability of the polymer-coated liposomes was investigated by evaluating the change in the retention of entrapped calcein after incubation at 20 and 37 °C.

Section snippets

Materials

Soya phosphatidylcholine (SPC) (self-made, ⩾98%), poly(vinyl alcohol) (95%, hydrolysis M.W.9500) was purchased from ACROS, Calcein and cholesterol were purchased from Sigma, water used as distilled twice. All other chemicals were reagent grade and used as received.

PVA-coated liposome

Liposomes composed of SPC and cholesterol were prepared by reverse phase evaporation method. SPC and cholesterol (1:1 molar ratio) dissolved in chloroform (3 ml) were taken in round-bottomed flask. It was then attached directly to the

Morphology

Fig. 1 shows the morphological characterization of liposomes and PVA modified liposomes. In all cases, the presence of spherical-shaped vesicles were predominant. When PVA is introduced to liposomes, a different trend in morphological change is observed. In contrast to Fig. 1a, much bigger vesicles (Fig. 1b and c) exist, resulting from the reorganization of SPC liposome with PVA modified.

Liposome size distribution

The particles sizes distribution for all liposome is shown in Fig. 2. We used liposomes without calcein in

Conclusion

The micrograph clearly showed the spherical shape of SPC liposomes and polymerized liposomes, the size, zeta potential and the adsorbing amount of polymer confirmed the thicker layer on the surface of the liposome. PVA-coated liposome and loaded liposome have larger entrapment efficiency and a prolonged period of release. Based on these results, a thicker polymer layer on the surface of liposomes is necessary to improve the physical stability.

Comparing with PVA-loaded liposomes, the coated

Acknowledgements

The authors would like to thank the Science Foundation of Guangdong province of China for financially supporting this research work under Grant 2KM02801G.

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Preparation and properties of poly(vinyl alcohol)-stabilized liposomes

Abstract

Introduction

Section snippets

Materials

PVA-coated liposome

Morphology

Liposome size distribution

Conclusion

Acknowledgements

Biochim. Biophys. Acta

J. Control Release

Biochim. Biophys. Acta

Trend. Biotechnol.

Int. J. Pharm.

Int. J. Pharm.

FEBS Lett.

J. Pharm. Sci.

TTBETECH

Curr. Opin. Solid State Mater. Sci.