Falconer Jonathan L, Christie R James, Pollard Emily J, Olsen Steven C, Grainger David W
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA.
Int J Pharm. 2016 Feb 10;498(1-2):187-94. doi: 10.1016/j.ijpharm.2015.12.040. Epub 2015 Dec 15.
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.
在许多全球场景中，弹道输送能力对于有效地向家畜和野生动物输送疫苗及其他治疗剂至关重要。在此，冻干的聚（乙二醇）（PEG）-乙交酯二甲基丙烯酸酯交联但可降解的水凝胶被评估为有效载荷载体，以保护并通过商业热塑性纤维素可降解生物子弹以弹道方式输送一种有活性的细菌疫苗——流产布鲁氏菌RB51菌株（RB51）。使用三种不同的聚合方法制备了装载约10¹⁰个活RB51细菌（CFU）的可降解PEG水凝胶棒，将其切成固定尺寸的有效载荷段并冻干。将所得致密、玻璃状的装载RB51疫苗的整块材料插入热塑性生物子弹100μL的有效载荷腔室中。作为时间和储存温度函数的冻干制剂的活力研究支持了几种条件产生可接受疫苗保质期的能力。从专门设计的气步枪发射时，装载凝胶的生物子弹表现出与未装载生物子弹相似的射程弹道特性（即动能、轨迹、精度）。这些水凝胶输送到牛组织后，通过在组织液中溶胀迅速再水化，在血清中5小时后观察到完全水化。活RB51疫苗在载体聚合、冻干和储存后表现出优异的活力，其水平足以对目标野生野牛进行疫苗接种。这些数据验证了冻干的可降解PEG水凝胶棒作为有用的药物载体，可使用弹道技术将活疫苗和其他治疗剂远程输送到家畜、野生动物或其他自由放养目标。
