creator Drapala, Pawel advisor Perez-Luna, Victor H. In this dissertation, we develop an injectable polymer system to enable localized and prolonged release of therapeutic biomolecules for improved treatment of Age-Related Macular Degeneration (AMD). Thermo-responsive hydrogels derived from N-isopropylacrylamide (NIPAAm) and cross-linked with poly(ethylene glycol) (PEG) poly(L-Lactic acid) (PLLA) copolymer were synthesized via free-radical polymerization. These materials were investigated for (a) phase change behavior, (b) in-vitro degradation, (c) capacity for controlled drug delivery, and (d) biocompatibility. The volume-phase transition temperature (VPTT) of the PNIPAAm-co-PEG- b-PLLA hydrogels was adjusted using hydrophilic and hydrophobic moieties so that it is ca. 33 C. These hydrogels did not initially show evidence of degradation at 37 C due to physical cross-links of collapsed PNIPAAm. Only after addition of glutathione chain transfer agents (CTA)s to the precursor did the collapsed hydrogels become fully soluble at at 37 C. CTAs signi cantly a ected the release kinetics of biomolecules; addition of 1.0 mg/mL glutathione to 3 mM cross-linker accelerated hydrogel degradation, resulting in 100 % release in less than 2 days. This work also explored the e ect of PEGylation in order to tether biomolecules to the polymer matrix. It was demonstrated that non-site-speci c PEGylation can postpone the burst release of solutes (up to 10 days in hydrogels with 0.5 mg/mL glutathione). Cell viability assays showed that at least two 20-minute bu er extraction steps were needed to remove cytotoxic elements from the hydrogels. Clinically-used therapeutic biomolecules Lucentis® and Avastin® were demonstrated to be both stable and bioactive after release form PNIPAAm-co-PEG-b-PLLA hydrogels. The thermo-responsive hydrogels presented here o er a promising platform for the localized delivery of proteins such as recombinant antibodies. Submitted by Dana Lamparello (dlampare@iit.edu) on 2012-02-28T17:28:41Z No. of bitstreams: 1 110420 pd thesis final.pdf: 2674881 bytes, checksum: 083a8382fd653f2306155cdb4dd78f57 (MD5) Made available in DSpace on 2012-02-28T17:28:41Z (GMT). No. of bitstreams: 1 110420 pd thesis final.pdf: 2674881 bytes, checksum: 083a8382fd653f2306155cdb4dd78f57 (MD5) Previous issue date: 2011-05 Ph.D. in Chemical and Biological Engineering, May 2011 2011-04-20 2011-05 http://hdl.handle.net/10560/2500 en Dissertation born digital application/pdf In Copyright http://rightsstatements.org/page/InC/1.0/ Restricted Access ChBE / Chemical and Biological Engineering Illinois Institute of Technology Affiliated department