Center for Research Development and Evaluation of Pharmaceutical Excipients and Generic Drugs, Department of Pharmaceutics, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
Department of Chemical Engineering, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, United States.
Biomaterials. 2018 Apr;160:107-123. doi: 10.1016/j.biomaterials.2018.01.022. Epub 2018 Feb 2.
Pneumonia is a major contributor to infection-based hospitalizations and deaths in the United States. Antibiotics such as azithromycin (AZM), although effective at managing pneumonia, often suffer from off-target diffusion and poor bioavailability when administered orally or via intravenous injection. The formation of biofilms at the disease sites makes the treatment more complicated by protecting bacteria from antimicrobial agents and thus necessitating a much higher dosage of antibiotics to eradicate the biofilms. As such, targeted pulmonary delivery of antibiotics has emerged as a promising alternative by providing direct access to the lung while also allowing higher local therapeutic concentrations but minimal systemic exposure. In this study, AZM was encapsulated in N-fumaroylated diketopiperazine (FDKP) microparticles for efficient pulmonary delivery. Both in vitro and in vivo results demonstrated that AZM@FDKP-MPs administered via intratracheal insufflation achieved at least a 3.4 times higher local concentration and prolonged retention times compared to intravenous injection and oral administration, suggesting their potential to better manage bacterial pneumonia.
肺炎是导致美国感染性住院和死亡的主要原因。尽管阿奇霉素（AZM）等抗生素在治疗肺炎方面有效，但口服或静脉注射时常常会出现非靶向扩散和生物利用度差的问题。在疾病部位形成生物膜会使治疗变得更加复杂，因为它可以保护细菌免受抗菌药物的侵害，因此需要更高剂量的抗生素来消灭生物膜。因此，抗生素的靶向肺部给药作为一种有前途的替代方法出现了，它可以直接进入肺部，同时允许更高的局部治疗浓度，但最小化全身暴露。在这项研究中，将阿奇霉素包封在富马酰化二酮哌嗪（FDKP）微球中，以实现有效的肺部递药。体内外实验结果表明，与静脉注射和口服给药相比，通过气管内滴注给予的阿奇霉素@FDKP-MP 至少实现了 3.4 倍的局部浓度提高和延长的滞留时间，这表明它们有可能更好地治疗细菌性肺炎。
