Photopolymerized hydrogel carriers for live vaccine ballistic delivery.

Photopolymerized poly(ethylene glycol) (PEG)-crosslinked hydrogels were assessed for their ability to serve as a payload vehicle to deliver a viable bacterial vaccine (Brucella abortus strain RB51 (RB51) to bison in Yellowstone National Park) ballistically using thermoplastic degradable Biobullets. PEG modified with degradable glycolide or lactide oligomers capped with photopolymerizable methacrylate groups served to crosslink the hydrogel vaccine carrier inside commercial hydroxypropylcellulose Biobullets. Release of 1 microm diameter model fluorescent particles from hydrogels followed known degradation trends for glycolide- and lactide-modified PEG hydrogels. All particles were released from PEG-co-glycolide hydrogels after approximately 10 days and PEG-co-lactide hydrogels after approximately 45 days following gel degradation. Minimal particle release was observed from pure PEG dimethacrylate hydrogels over 40 days. P. aeruginosa (strain PAO1) and RB51 live vaccines exhibit excellent viability following exposure to photopolymerization encapsulation within these gel matrices. Hydrogels photopolymerized into the payload chamber of Biobullets exhibit similar ballistic properties to commercially available Biobullets and penetrate and remain intact when fired intramuscularly into live elk for release of their gel payload in the host.

Design and synthesis of a new polymer drug delivery conjugate.

This work describes the design and synthesis of a novel polymer conjugate to facilitate intracellular release of attached cargo. Water soluble poly[N(2-hydroxypropyl) methacrylamide] with derivatizable pendant side chains was used as the polymer carrier. The membrane active Tat peptide was masked with poly(ethylene glycol) to inhibit non-specific interactions with exterior cell membranes, and then covalently linked to poly[N-(2-hydroxypropyl) methacrylamide]. A novel heterobifunctional crosslinker was synthesized containing both maleimide and aldehyde functionality to allow attachment of peptides to the polymer backbone through a pH sensitive bond. Analysis of the proposed conjugate by gel permeation chromatography, nuclear absorbance spectroscopy, and absorbance measurements indicate that the desired compound has been synthesized.