Stability of proteins within biodegradable microspheres

In the past decade, biodegradable polymers have become the materials of choice for a variety of biomaterials applications. In particular, poly(lactic-co-glycolic acid) (PLGA) microspheres have been extensively studied for controlled-release protein delivery. However, significant issues arise in formulating such delivery systems since few proteins have been successfully encapsulated and released from these microspheres. Here, methods are developed to determine the causes of protein instability and solutions are provided for overcoming these problems. A commonly used technique for protein encapsulation in PLGA microspheres is the double-emulsion method. The harsh processing associated with this method can cause denaturation of the encapsulated protein. Herein, we have used Fourier transform infrared (FTIR) spectroscopy to determine the secondary structures of two model proteins, bovine serum albumin (BSA) and chicken egg-white lysozyme, within PLGA microspheres. This is a novel technique for in situ evaluation of proteins within microspheres and potentially a powerful and quick method for assessment of formulations. Results for both proteins indicate changes in structure upon entrapment within the microspheres. However, addition of the stabilizing excipient trehalose prevents the denaturing effects incurred during processing. In addition, BSA released from microspheres is improved by incorporation of trehalose. With microspheres made by double emulsion, there is often a large, initial burst of drug release upon injection. This results in inefficient use of therapy. To prevent this loss, a modified spontaneous emulsification method was explored.

Department dc:contributor.department

Harvard University--MIT Division of Health Sciences and Technology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2000

Author dc:creator

• Fu, Karen, 1967-

Advisor dc:contributor.advisor

• Robert S. Langer and Alexander M. Klibanov.

• Harvard University--MIT Division of Health Sciences and Technology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/8422

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/8422