Shaaban Mona I, Shaker Mohamed A, Mady Fatma M
Pharmaceutics and Pharmaceutical Technology Department, College of Pharmacy, Taibah University, PO Box 30040, Al Madina, Al Munawara, Saudi Arabia.
Microbiology and Immunology Department, Faculty of Pharmacy, Mansoura University, PO Box 35516, Mansoura, Egypt.
J Nanobiotechnology. 2017 Apr 11;15(1):29. doi: 10.1186/s12951-017-0262-9.
Carbapenem-resistance is an extremely growing medical threat in antibacterial therapy as the incurable resistant strains easily develop a multi-resistance action to other potent antimicrobial agents. Nonetheless, the protective delivery of current antibiotics using nano-carriers opens a tremendous approach in the antimicrobial therapy, allowing the nano-formulated antibiotics to beat these health threat pathogens. Herein, we encapsulated imipenem into biodegradable polymeric nanoparticles to destroy the imipenem-resistant bacteria and overcome the microbial adhesion and dissemination. Imipenem loaded poly Ɛ-caprolactone (PCL) and polylactide-co-glycolide (PLGA) nanocapsules were formulated using double emulsion evaporation method. The obtained nanocapsules were characterized for mean particle diameter, morphology, loading efficiency, and in vitro release. The in vitro antimicrobial and anti adhesion activities were evaluated against selected imipenem-resistant Klebsiella pneumoniae and Pseudomonas aeruginosa clinical isolates.
The obtained results reveal that imipenem loaded PCL nano-formulation enhances the microbial susceptibility and antimicrobial activity of imipenem. The imipenem loaded PCL nanoparticles caused faster microbial killing within 2-3 h compared to the imipenem loaded PLGA and free drug. Successfully, PCL nanocapsules were able to protect imipenem from enzymatic degradation by resistant isolates and prevent the emergence of the resistant colonies, as it lowered the mutation prevention concentration of free imipenem by twofolds. Moreover, the imipenem loaded PCL eliminated bacterial attachment and the biofilm assembly of P. aeruginosa and K. pneumoniae planktonic bacteria by 74 and 78.4%, respectively.
These promising results indicate that polymeric nanoparticles recover the efficacy of imipenem and can be considered as a new paradigm shift against multidrug-resistant isolates in treating severe bacterial infections.
碳青霉烯耐药性在抗菌治疗中是一个日益严重的医学威胁，因为无法治愈的耐药菌株很容易对其他强效抗菌剂产生多重耐药作用。尽管如此，使用纳米载体对现有抗生素进行保护性递送为抗菌治疗开辟了一条极具潜力的途径，使纳米制剂抗生素能够战胜这些对健康构成威胁的病原体。在此，我们将亚胺培南封装到可生物降解的聚合物纳米颗粒中，以杀灭耐亚胺培南细菌，并克服微生物的黏附和传播。采用双乳液蒸发法制备了负载亚胺培南的聚ε-己内酯（PCL）和聚乳酸-羟基乙酸共聚物（PLGA）纳米胶囊。对所制备的纳米胶囊进行了平均粒径、形态、载药效率和体外释放等特性表征。针对所选的耐亚胺培南肺炎克雷伯菌和铜绿假单胞菌临床分离株，评估了其体外抗菌和抗黏附活性。
所得结果表明，负载亚胺培南的PCL纳米制剂提高了亚胺培南的微生物敏感性和抗菌活性。与负载亚胺培南的PLGA和游离药物相比，负载亚胺培南的PCL纳米颗粒在2 - 3小时内就能更快地杀灭微生物。成功的是，PCL纳米胶囊能够保护亚胺培南不被耐药菌株酶解，并防止耐药菌落的出现，因为它将游离亚胺培南的防突变浓度降低了两倍。此外，负载亚胺培南的PCL分别使铜绿假单胞菌和肺炎克雷伯菌浮游菌生物膜的形成和细菌黏附减少了74%和78.4%。
这些令人鼓舞的结果表明，聚合物纳米颗粒恢复了亚胺培南的疗效，可被视为治疗严重细菌感染中对抗多重耐药菌株的一种新的范式转变。
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