Edwards Alexander D, Slater Nigel K H
Department of Chemical Engineering and Biotechnology, University of Cambridge, New Museums Site, Cambridge CB2 3RA, UK.
Vaccine. 2009 Jun 12;27(29):3897-903. doi: 10.1016/j.vaccine.2009.04.006. Epub 2009 Apr 23.
We previously demonstrated that a dry, room temperature stable formulation of a live bacterial vaccine was highly susceptible to bile, and suggested that this will lead to significant loss of viability of any live bacterial formulation released into the intestine using an enteric coating or capsule. We found that bile and acid tolerance is very rapidly recovered after rehydration with buffer or water, raising the possibility that rehydration in the absence of bile prior to release into the intestine might solve the problem of bile toxicity to dried cells. We describe here a novel formulation that combines extensively studied bile acid adsorbent resins with the dried bacteria, to temporarily adsorb bile acids and allow rehydration and recovery of bile resistance of bacteria in the intestine before release. Tablets containing the bile acid adsorbent cholestyramine release 250-fold more live bacteria when dissolved in a bile solution, compared to control tablets without cholestyramine or with a control resin that does not bind bile acids. We propose that a simple enteric coated oral dosage form containing bile acid adsorbent resins will allow improved live bacterial delivery to the intestine via the oral route, a major step towards room temperature stable, easily administered and distributed vaccine pills and other bacterial therapeutics.
我们之前证明，一种干燥、室温稳定的活细菌疫苗制剂对胆汁高度敏感，并表明这将导致任何使用肠溶包衣或胶囊释放到肠道中的活细菌制剂的活力显著丧失。我们发现，用缓冲液或水复水后，胆汁和酸耐受性能非常迅速地恢复，这增加了在释放到肠道之前在无胆汁情况下复水可能解决胆汁对干燥细胞毒性问题的可能性。我们在此描述一种新型制剂，它将经过广泛研究的胆汁酸吸附树脂与干燥细菌相结合，以暂时吸附胆汁酸，并在释放前使细菌在肠道中复水并恢复胆汁抗性。与不含消胆胺或含有不结合胆汁酸的对照树脂的对照片剂相比，含有胆汁酸吸附剂消胆胺的片剂在胆汁溶液中溶解时释放的活细菌多250倍。我们提出，一种含有胆汁酸吸附树脂的简单肠溶口服剂型将允许通过口服途径将活细菌更好地递送至肠道，这是朝着室温稳定、易于给药和分发的疫苗丸及其他细菌疗法迈出的重要一步。
