Madbouly Neveen Adel, Nashee Hayam, Elgendy Ashraf Ahmed, Rabee Ibraheem, El Amir Azza
Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt.
Chemistry Laboratory, Abou El Nomros Central Hospital, Giza, Egypt.
Infect Chemother. 2020 Dec;52(4):550-561. doi: 10.3947/ic.2020.52.4.550.
The present study was designed to investigate the antigiardial efficacy of low metronidazole dose loaded-D.L-lactide-co-glycolide (LMD-PLGA) nanoparticles (NPs) and to compare it with the standard high dose of metronidazole either free (HMD) or loaded on PLGA (HMD-PLGA).
PLGA NPs were prepared by single emulsification method, metronidazole (MTZ) was loaded in low and high doses. The nanoparticles were evaluated for mice model. The infected mice were treated by LMD and HMD either free or PLGA NPs loaded, the parasitic load and ployclonal antigiardial serum antibodies (IgG and IgA) were recorded. Histopathological studies on intestinal and liver sections were applied.
MTZ-PLGA NPs was successfully prepared with 81.68% encapsulation efficiency and with an average particle size of approximately 228.00 ± 43.19 nm and -32.28 ± 0.07 mV Zeta potential. Experimentally, it was observed that infected animals administered with LMD-PLGA had completely eliminated cyst shedding and trophozoite count compared with -infected mice. Further, it was found that animals belonging to LMD-PLGA group had significantly reduced levels of antigiardial IgA (0.99 ± 0.05) antibodies in serum compared with -infected. Histopathologyically, also animals belonging to LMD-PLGA treated group had intact mucosal epithelium lining, and normal villi with no detection of trophozoites. In addition to the less toxic effect on the liver tissue compared to free HMD, HMD-PLGA and infected-untreated groups using Ishak grading system.
Our study showed that PLGA nanoparticles could be atrial delivery systems for antigiardial drugs to improve their therapeutic efficacy and minimize their side effects that results from frequent dosing.
本研究旨在探究低剂量甲硝唑负载的聚乳酸-羟基乙酸共聚物(LMD-PLGA)纳米颗粒(NPs)的抗贾第虫疗效,并将其与标准高剂量的游离甲硝唑(HMD)或负载于PLGA的甲硝唑(HMD-PLGA)进行比较。
采用单乳化法制备PLGA NPs,分别负载低剂量和高剂量的甲硝唑。对小鼠模型进行纳米颗粒评估。用游离或负载PLGA NPs的LMD和HMD治疗感染小鼠,记录寄生虫负荷和多克隆抗贾第虫血清抗体(IgG和IgA)。对肠道和肝脏切片进行组织病理学研究。
成功制备了MTZ-PLGA NPs,包封率为81.68%,平均粒径约为228.00±43.19 nm,Zeta电位为-32.28±0.07 mV。实验观察到,与未感染小鼠相比,给予LMD-PLGA的感染动物完全消除了囊肿脱落和滋养体计数。此外,发现LMD-PLGA组动物血清中的抗贾第虫IgA抗体水平(0.99±0.05)与未感染动物相比显著降低。组织病理学上,LMD-PLGA治疗组动物的黏膜上皮内衬完整,绒毛正常,未检测到滋养体。与游离HMD、HMD-PLGA和未治疗的感染组相比,LMD-PLGA对肝脏组织的毒性作用更小(使用Ishak分级系统)。
我们的研究表明,PLGA纳米颗粒可作为抗贾第虫药物的心房给药系统,以提高其治疗效果并最大限度地减少频繁给药引起的副作用。