title: Live RB51 vaccine lyophilized hydrogel formulations with increased shelf life for practical ballistic delivery.
abstract: Ballistic delivery capability is essential to delivering vaccines and other therapeutics effectively to both livestock and wildlife in many global scenarios. Here, lyophilized poly(ethylene glycol) (PEG)-glycolide dimethacrylate crosslinked but degradable hydrogels were assessed as payload vehicles to protect and deliver a viable bacterial vaccine, Brucella abortus strain RB51 (RB51), ballistically using commercial thermoplastic cellulosic degradable biobullets. Degradable PEG hydrogel rods loaded with ∼10(10) live RB51 bacteria (CFUs) were fabricated using three different polymerization methods, cut into fixed-sized payload segments, and lyophilized. Resulting dense, glassy RB51 vaccine-loaded monoliths were inserted into thermoplastic biobullet 100-μL payload chambers. Viability studies of lyophilized formulations assessed as a function of time and storage temperature supported the abilities of several conditions to produce acceptable vaccine shelf-lives. Fired from specifically designed air rifles, gel-loaded biobullets exhibit down-range ballistic properties (i.e., kinetic energy, trajectory, accuracy) similar to unloaded biobullets. Delivered to bovine tissue, these hydrogels rehydrate rapidly by swelling in tissue fluids, with complete hydration observed after 5h in serum. Live RB51 vaccine exhibited excellent viability following carrier polymerization, lyophilization, and storage, at levels sufficient for vaccine dosing to wild range bison, the intended target. These data validate lyophilized degradable PEG hydrogel rods as useful drug carriers for remote delivery of both live vaccines and other therapeutics to livestock, wildlife, or other free-range targets using ballistic technologies.
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Falconer
authors.affiliation: Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: R James
authors.initials: RJ
authors.lastname: Christie
authors.affiliation: Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Pollard
authors.affiliation: Bacterial Diseases of Livestock Research Unit, National Animal Disease Center, USDA/ARS, Ames, IA 50010, USA.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Olsen
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA. Electronic address: david.grainger@utah.edu.
authors.forename: David W
authors.initials: DW
authors.lastname: Grainger
mesh_terms: D000818:Animals; D002003:Brucella abortus / Q000737:chemistry*; D002417:Cattle; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems / Q000379:methods*; D004343:Drug Implants / Q000008:administration & dosage / Q000737:chemistry*; D004355:Drug Stability; D005612:Freeze Drying / Q000379:methods; D020100:Hydrogels / Q000008:administration & dosage / Q000737:chemistry*; D014611:Vaccination / Q000379:methods*
chemical_list: D004343:Drug Implants; D020100:Hydrogels
keywords: Animal health; Bio-bullet; Bison; Brucellosis; Polyethylene glycol; Polymerization; Remote delivery; Wildlife