Swelling lecithin: cholesterol implants for the controlled release of proteins

Abstract

This work demonstrated the effect of two salts as potential simple formulation excipients in modifying hydration properties, phase behavior, and protein release from lecithin-based implants. In vitro release of a model protein, bovine serum albumin (BSA), from cylindrical-shaped lecithin and lecithin:cholesterol (1:1 w/w) implants containing 0, 10, or 30% w/w NaCl or CaCl₂ was studied. In the absence of salts, BSA was released from lecithin and lecithin:cholesterol implants with a high monomer content and the release profiles were similar to those previously reported. Cholesterol increased the swelling, induced the formation of myelin structures, and reduced BSA release from the matrices. Addition of the salts to lecithin:cholesterol implants further enhanced the swelling, altered the hydrated morphology, and inhibited protein release. Analyses showed that BSA associated into multimers within these swollen lipid matrices but retained a high degree of protein native structure. Factors that may have contributed to the inhibition of the in vitro release included 1) the swollen multilamellar layers assembled as diffusional barriers, 2) adsorption of BSA onto the hydrated lipid vesicles, and 3) formation of protein aggregates.

Keywords::

• Controlled release
• protein
• lecithin:cholesterol
• salt
• swellable
• solid implants

Acknowledgments

The authors would like to thank the School of Pharmacy, University of Otago, for a PhD stipend for R.T. This work was carried out with financial support from a University of Otago Research Grant.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.