title: Imipenem/cilastatin encapsulated polymeric nanoparticles for destroying carbapenem-resistant bacterial isolates.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Mona I
authors.initials: MI
authors.lastname: Shaaban
authors.affiliation: Pharmaceutics and Pharmaceutical Technology Department, College of Pharmacy, Taibah University, PO Box 30040, Al Madina, Al Munawara, Saudi Arabia. mshaker@mun.ca.|Pharmaceutics Department, Faculty of Pharmacy, Helwan University, PO Box 11795, Cairo, Egypt. mshaker@mun.ca.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Shaker
authors.affiliation: Pharmaceutics and Pharmaceutical Technology Department, College of Pharmacy, Taibah University, PO Box 30040, Al Madina, Al Munawara, Saudi Arabia.|Pharmaceutics Department, Faculty of Pharmacy, El-Minia University, El-Minia, Egypt.
authors.forename: Fatma M
authors.initials: FM
authors.lastname: Mady
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001422:Bacterial Adhesion / Q000187:drug effects; D001424:Bacterial Infections / Q000188:drug therapy; D018441:Biofilms / Q000187:drug effects; D015377:Cilastatin / Q000494:pharmacology*; D000077728:Cilastatin, Imipenem Drug Combination; D004337:Drug Carriers / Q000737:chemistry; D004338:Drug Combinations; D024901:Drug Resistance, Multiple, Bacterial; D015378:Imipenem / Q000494:pharmacology*; D007711:Klebsiella pneumoniae / Q000187:drug effects*; D019344:Lactic Acid / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D018440:beta-Lactam Resistance
chemical_list: D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D004338:Drug Combinations; D011091:Polyesters; D015377:Cilastatin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C016240:polycaprolactone; D011100:Polyglycolic Acid; D019344:Lactic Acid; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination
keywords: Antibiotic resistance; Biodegradable; Imipenem; Nanoparticles; PCL; PLGA