Modulated Drug Delivery and Gene Therapy:

Above a critical gelation temperature and polymer concentration, the micelles formed by the multi-block copolymers described above self-assemble to form macroscale thermoreversible physical gels. Since the critical gelation temperatures are close to room temperature, these polymers can be used as injectable delivery devices and have significant advantages over other crosslinked stimuli-sensitive hydrogels that have been investigated. These physical gels eventually dissolve in the body. The copolymers also exhibit significantly reduced cytotoxicities compared to the parent cationic homopolymers. These polymers are ideal candidates for self-regulating systems for drug delivery. We have obtained insights into dissolution and release mechanisms from these and other gels using novel diffusional and spectroscopic techniques coupled with predictive models. These cationic polymers exhibit complexation with DNA and serve as excellent injectable controlled gene delivery vectors. 

Templates for Biomineralization:

This new multi-investigator project focuses on growing magnetite nanocrystals using our hierarchically self-assembled polymers described above, using aptamers and mineralization proteins. This approach aims to recreate the structure of magnetite nanocrystals embedded in organic tissue seen in many different living species, that confers super-paramagnetic properties. The combination of the “soft” mechanical properties of the polymer with the strong magnetic response of the magnetite offers new materials properties like giant shape memory effects, field induced deformations, or a magnetic field tuned sound spectrum.

Publications

•  Peleshanko, S., Anderson , K. D., Goodman, M., Determan, M. D., Mallapragada, S.K., and Tsukruk, V., “Thermoresponsive Behavior of Multistimuli Pluronic ® -based Pentablock Copolymers at the Air-Water Interface”, Langmuir (submitted)

•  Prozorov, T., Mallapragada, S.K., Narasimhan, B., Nilsen-Hamilton, M., Williams, T. J., Bazylinski, D., Prozorov, R., and Canfield, P.C., “ Protein-Mediated Synthesis of Superparamagnetic Magnetite Nanocrystals”, Adv. Func. Mater. (in press).

•  Determan, M.D., Cox, J. P. and Mallapragada, S.K., “Drug Release from pH-Responsive Thermogelling Pentablock Copolymers ”, J. Biomed. Mater. Res . (in press).

•  Determan, M. D., Thiyagarajan, P. and Mallapragada, S.K., “Supramolecular Self-assembly of Multiblock Copolymers in Solution”, Langmuir , 22 , 1469-1473 (2006).

•  Agarwal, A., Unfer, R. C., and Mallapragada, S. K., “Novel Cationic Pentablock Copolymers as Non Viral Vectors for Gene Delivery”, J. Control. Rel ., 103 , 245-258 (2005).

•  Determan, M. D. and Mallapragada, S. K., “Self-assembling Nanostructured Injectable Polymeric Gels for Drug Delivery”, in Handbook of Nanostructured Biomaterials and Their Applications”, Nalwa, H. S. (ed.), American Scientific, Los Angeles , CA , Vol.2, pp 458-471 (2005).

•  Anderson, B. C., Cox, S. M., Bloom, P.D, Sheares, V. V., and Mallapragada, S.K., “Synthesis and Characterization of Diblock and Gel Forming Pentablock Copolymers of Tertiary Amine Methacrylates, Poly(Ethylene Glycol) and Poly(Propylene Glycol)”, Macromolecules, 36 , 1670-76 (2003).

•  Anderson , B.C, and Mallapragada, S.K., “Synthesis and Characterization of Injectable, Water-soluble Copolymers of Tertiary Amine Methacrylates and Poly(Ethylene Glycol) Containing Methacrylates”, Biomaterials , 23 , 4345-59 (2002).

•  Anderson , B.C, Cox, S.M., Ambardekar, A., and Mallapragada, S.K., “Effect of Salts on the Micellization Temperature of Aqueous Poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) Solutions and the Dissolution Rate and Water Diffusion Coefficient in their Corresponding Gels”, J. Pharm. Sci. , 91 , 180-188 (2002).

•  Anderson, B., Amanda, A., and Mallapragada, S.K., “Microencapsulation Methods Using Poly(vinyl alcohol)”, in Methods of Tissue Engineering , Atala, A., and Lanza, R., (Eds.), Chap.74, pp. 835-839, Academic Press, San Diego, CA (2001).

•  Anderson, B.C, Bloom, P.D., Sheares, V.V. and Mallapragada, S.K., “Synthesis and Characterization of Water Soluble Block Copolymers for pH Sensitive Drug Delivery”, in Biomaterials for Drug Delivery and Tissue Engineering, Eds. Mallapragada, S.K., Tracy, M., Narasimhan, B., Mathiowitz, E., and Korsmeyer, R., Materials Research Society Symp. Ser, 662 (2001).