Biodegradable and Soluble Polymers for Sustained Drug and Protein Delivery
Maria Torres
This thrust deals with the development of biodegradable polyanhydrides for drug and protein delivery and stabilization. Part of this effort involves development of combinatorial approaches for synthesis of these copolymers and high-throughput methods for testing drug release profiles from polymers.
Combinatorial Synthesis of Polyanhydrides for Drug Delivery: The overall goal of this project is to design novel biodegradable nanocarriers for protein stabilization and immune modulation. We have synthesized random copolymers of various anhydride monomers, which play a major role in polypeptide stabilization and vaccine delivery. We have developed high-throughput strategies for synthesizing libraries of polyanhydride copolymers simultaneously. These libraries of copolymers with various compositions are being screened rapidly to obtain information about phase behavior as well as release profiles. We have synthesized a library of 100 different polyanhydride copolymers and characterized it using FTIR microscopy. Altogether, this integrated approach will provide novel insights into the mechanisms of adjuvanticity and tailor the chemistry and size of the biodegradable nanoadjuvants to elicit appropriate immune responses. |
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Polyanhydrides for Protein Delivery: We have synthesized modified polyanhydrides that contain oligoethyeleneglycol units in the monomers to control the amphiphilic balance in the resulting copolymers to enable protein stabilization. These copolymers are being explored for protein and vaccine delivery and have been shown to modulate the immune response. |
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Publications |
• Torres, M. P., Mallapragada, S. K., and Narasimhan, B., “Protein Stabilization and Release from Novel Amphiphilic Polyanhydrides”, Biomaterials (submitted). |
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• Torres, M., Vogel, B., Narasimhan, B. and Mallapragada, S.K., “Erosion Mechanism of Novel Polyanhydrides Containing Oligomeric Ethylene Glycol”, J . Biomed. Mater. Res ., 76A , 102-110 (2006). |
Reprint |
| • Vogel, B., Eidelman, N., Narasimhan, B. and Mallapragada, S.K., “Parallel Synthesis and Dissolution Testing of Polyanhydride Random Copolymers”, J. Comb. Chem., 7 , 921-28 (2005). | Reprint |
• Torres, M. P., Determan, A., Mallapragada, S.K. and Narasimhan, B., “Polyanhydrides”, in Encyclopedia of Chemical Processing , Taylor and Francis, (in press). |
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• Vogel, B., and Mallapragada, S. K., “Synthesis of Novel Biodegradable Polyanhydrides Containing Aromatic and Glycol Functionality for Tailoring of Hydrophilicity in Controlled Drug Delivery Devices”, Biomaterials , 26 , 721-728 (2005). |
Reprint |
| • Vogel, B. and Mallapragada, S. K., “Synthesis of Polyanhydrides”, in Handbook of Biodegradable Polymeric Materials and Their Applications , Eds. Mallapragada, S.K. and Narasimhan, B., Vol. 1, American Scientific, Los Angeles, CA, pp. 329-347 (2005). | |
| • Mallapragada, S.K., Vogel, B. and Narasimhan, B., “Combinatorial Methods for Synthesis and Characterization of Polyanhydride Copolymer ”, Polym. Mater. Sci. Eng. Proceed. , 93 , 818-819 (2005). | |
| • M.P. Torres, B. Narasimhan, and S.K. Mallapragada, “A New Class of “Bulk Erodible” Polyanhydrides,” Polym. Prepr. , 46(1) , 234-235 (2005). | |
• Vogel, B., Mallapragada, S. K., and Narasimhan, B., “ Rapid Synthesis of Polyanhydrides by Microwave Polymerization”, Macromol. Rapid Comm ., 25 , 330-333 (2004). |
Reprint |
| • Mallapragada, S. K. and McCarthy-Schroeder, S., “Poly(vinyl alcohol) as a Drug Delivery Carrier”, in Handbook of Pharmaceutical Controlled Release Technology , Wise, D. L. (Ed.), pp. 31-47, Marcel Dekker, New York, NY (2000). | |
| • Mallapragada, S. K. , and Chin, S. –F., “Multilayered Semicrystalline Polymeric Controlled Release Systems”, in Materials for Controlled Drug Delivery Applications , Ed. McCulloch, I., American Chemical Society Ser., 709 , 176-184 (1998). | |
• Sondhof, A. F., Mallapragada, S. K., Booth, L. C., Heath, C. A., Rosenbuch, R., Apley, M., and Hsu, W., “Poly(lactic acid) Biodegradable Microspheres for Sustained Antimicrobial Drug Release in the Equine Joint: Preliminary In vivo Results”, Proceed. Intern. Symp. Control. Rel. Bioact. Mater., 25 , 651-652(1998). |
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| • Mallapragada, S. K., and Narasimhan, B., “Drug Delivery Systems”, in Handbook of Biomaterials Evaluation , von Recum, A. (Ed.), Taylor and Francis, NY, Chap. 27 ., pp. 425-437 (1998). | |
| • Mallapragada, S. K. and Peppas, N. A. , “ Crystal Dissolution-Controlled Release Systems: I. Physical Characteristics and Modeling Analysis”, J. Controlled Rel., 45 , 87-94 (1997). | Reprint |
| • Mallapragada, S. K., Peppas, N. A. , and Colombo , P., “Crystal Dissolution Controlled Release Systems: II. Metronidazole Release From Semicrystalline Poly(vinyl alcohol)”, J. Biomed. Mater. Res. , 36 , 125-130 (1997). | Reprint |
• Mallapragada, S. K., and Chin, S. –F., “Multilayered Crystal-Dissolution Controlled Release Systems for Drug Delivery”, Polym. Prep. , 38 (2) , 622-623 (1997). |
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• Mallapragada, S. K., Peppas, N. A. , and Colombo, P., “Modification of Drug Release Profiles and Swelling Behavior in Poly(vinyl alcohol) Due to the Presence of a Crystalline Phase”, Polym. Mater. Sci. Eng. Proceed, 74 , 416-417 (1996). |
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• Peppas, N. A., and Mallapragada, S. K., “ Crystal Dissolution-Controlled Release Systems: A Novel Technology for Facile Programmed Release of Drugs”, Proceed. Adv. Control. Deliv. 1 , 89-90 (1996). |