Barsoum I S, Kopydlowski K M, Cuenin P, Setterstrom J A
US Army Dental Research Detachment, Walter Reed Army Institute of Research, Washington, DC 20307-5300, USA.
J Antimicrob Chemother. 1997 Jan;39(1):63-9. doi: 10.1093/jac/39.1.63.
The purpose of this study was to determine if the sustained release of ampicillin from a biodegradable drug-delivery system (microencapsulated ampicillin anhydrate (MEAA)) will increase or decrease the intensity of a hypersensitivity reaction compared with that observed with free drug. Ovalbumin, which is known to elicit a marked hypersensitivity reaction in guinea pigs, and microencapsulated ovalbumin (MOVA) were tested in parallel with ampicillin and MEAA. Guinea pigs were sensitized biweekly by subcutaneous and intramuscular injections of ampicillin, MEAA, ovalbumin, MOVA or placebo microspheres (test articles), each mixed with Freund's adjuvant, and challenged 2 weeks later, intradermally, with the free compounds. In a separate set of experiments, guinea pigs were sensitized by implantation of the same agents in the caudal thigh of anaesthetized animals. Skin allergic reactions were tested at 1 and 3 weeks following local implantation of the test articles. Sera of sensitized guinea pigs were tested for specific IgG antibodies by enzyme-linked immunosorbent assay, and skin samples from the site of the inflammatory reaction were fixed, stained and evaluated histologically. Guinea pigs sensitized systemically with MEAA or MOVA showed smaller, but not statistically different skin allergic response than animals given corresponding free compounds. However, guinea pigs sensitized by local implantation of MEAA showed a significantly lower inflammatory response (P < 0.0001) than those given an equivalent dose of the free drug. Guinea pigs sensitized with placebo microspheres showed a low inflammatory skin reaction which was similar to those sensitized with all doses of MEAA. There was no significant difference in specific IgG antibody response in the sera of guinea pigs sensitized locally with either free or microencapsulated ampicillin or ovalbumin. Histology of skin revealed a milder inflammatory reaction with MEAA or MOVA than with ampicillin or ovalbumin, respectively. We conclude that the encapsulated ampicillin or ovalbumin and subsequent release of each agent will elicit a reduced hypersensitivity reaction in guinea pigs than will the free agent.
本研究的目的是确定与游离药物相比，氨苄西林从可生物降解给药系统（微囊化无水氨苄西林（MEAA））中的持续释放是否会增加或降低超敏反应的强度。已知卵清蛋白可在豚鼠中引发明显的超敏反应，微囊化卵清蛋白（MOVA）与氨苄西林和MEAA同时进行测试。豚鼠每两周通过皮下和肌肉注射氨苄西林、MEAA、卵清蛋白、MOVA或安慰剂微球（受试物）进行致敏，每种受试物均与弗氏佐剂混合，并在2周后皮内注射游离化合物进行激发。在另一组实验中，豚鼠通过在麻醉动物的尾侧大腿植入相同的药物进行致敏。在局部植入受试物后1周和3周测试皮肤过敏反应。通过酶联免疫吸附测定法检测致敏豚鼠血清中的特异性IgG抗体，并对炎症反应部位的皮肤样本进行固定、染色和组织学评估。与给予相应游离化合物的动物相比，用MEAA或MOVA进行全身致敏的豚鼠表现出较小但无统计学差异的皮肤过敏反应。然而，通过局部植入MEAA致敏的豚鼠比给予等量游离药物的豚鼠表现出显著更低的炎症反应（P<0.0001）。用安慰剂微球致敏的豚鼠表现出低炎症皮肤反应，这与用所有剂量的MEAA致敏的豚鼠相似。局部用游离或微囊化氨苄西林或卵清蛋白致敏的豚鼠血清中特异性IgG抗体反应无显著差异。皮肤组织学显示，与氨苄西林或卵清蛋白相比，MEAA或MOVA引起的炎症反应更轻。我们得出结论，与游离药物相比，包裹的氨苄西林或卵清蛋白以及每种药物的后续释放将在豚鼠中引发更低的超敏反应。
