Jose L Rios1, Gongcheng Lu1, Na Eun Seo2, Tamara Lambert2, David Putnam3,4. 1. Meinig School of Biomedical Engineering, Cornell University, 147 Weill Hall, Ithaca, New York, 14853, USA. 2. Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York, 14853, USA. 3. Meinig School of Biomedical Engineering, Cornell University, 147 Weill Hall, Ithaca, New York, 14853, USA. dap43@cornell.edu. 4. School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York, 14853, USA. dap43@cornell.edu.
Abstract
PURPOSE: Therapeutic proteins have become an integral part of health care. However, their controlled delivery remains a challenge. Protein function depends on a delicate three dimensional structure, which can be damaged during the fabrication of controlled release systems. This study presents a microgel-based controlled release system capable of high loading efficiencies, prolonged release and retention of protein function. METHODS: A new DMSO/Pluronic microemulsion served as a reaction template for the crosslinking of poly(acrylic acid) and oligo (ethylene glycol) to form microgels. Poly(acylic acid) molecular weights and microgel crosslinking densities were altered to make a series of microgels. Microgel capacity to capture and retain proteins of different sizes and isoelectric points, to control their release rate (over ~30 days) and to maintain the biofunctionality of the released proteins were evaluated. RESULTS: Microgels of different sizes and morphologies were synthesized. Loading efficiencies of 100% were achieved with lysozyme in all formulations. The loading efficiency of all other proteins was formulation dependent. Release of lysozyme was achieved for up to 30 days and the released lysozyme retained over 90% of its activity. CONCLUSIONS: High loading efficiencies and prolonged release of different proteins was achieved. Furthermore, lysozyme's functionality remained uncompromised after encapsulation and release. This work begins to lay the foundation for a broad platform for the delivery of therapeutic proteins.
PURPOSE: Therapeutic proteins have become an integral part of health care. However, their controlled delivery remains a challenge. Protein function depends on a delicate three dimensional structure, which can be damaged during the fabrication of controlled release systems. This study presents a microgel-based controlled release system capable of high loading efficiencies, prolonged release and retention of protein function. METHODS: A new DMSO/Pluronic microemulsion served as a reaction template for the crosslinking of poly(acrylic acid) and oligo (ethylene glycol) to form microgels. Poly(acylic acid) molecular weights and microgel crosslinking densities were altered to make a series of microgels. Microgel capacity to capture and retain proteins of different sizes and isoelectric points, to control their release rate (over ~30 days) and to maintain the biofunctionality of the released proteins were evaluated. RESULTS: Microgels of different sizes and morphologies were synthesized. Loading efficiencies of 100% were achieved with lysozyme in all formulations. The loading efficiency of all other proteins was formulation dependent. Release of lysozyme was achieved for up to 30 days and the released lysozyme retained over 90% of its activity. CONCLUSIONS: High loading efficiencies and prolonged release of different proteins was achieved. Furthermore, lysozyme's functionality remained uncompromised after encapsulation and release. This work begins to lay the foundation for a broad platform for the delivery of therapeutic proteins.
Authors: Sotirios Koutsopoulos; Larry D Unsworth; Yusuke Nagai; Shuguang Zhang Journal: Proc Natl Acad Sci U S A Date: 2009-03-09 Impact factor: 11.205