Formulation And Characterization Of Pyochelin Conjugated Liposome Oleic Acid CoEncapsulated With Antibiotics Against Multi Drug Resistant Pseudomonas Aeruginosa

Abstract

Microbial resistance to various antibiotics is one of the major health problems globally. An efficient antibiotic delivery approach is highly essential to fight bacterial resistance. Encapsulating the antibiotics (Ab) into nanocarrier molecules is a promising strategy to deliver the drugs to the infection site. Liposomes are potential pharmaceutical carriers widely used to encapsulate various therapeutic agents due to its enhanced stability and reduced toxicity. In this scenario, the aim of the study was to engineer a biodegradable liposome antibiotic complex to specifically target and eradicate multidrug resistant Pseudomonas aeruginosa (MDRPa). Liposomes were prepared by thin film hydration method with their stability enhanced by the addition of oleic acid (OA) in its hydrophobic layer. Among 223 samples collected from various clinical sources such as pus, sputum, urine and ear swab, 76 positive P. aeruginosa isolates were recovered and tested for its virulence against piperacillin-tazobactam, imipenem, gentamicin, tobramycin, cephalexin, ampicillin, nitrofurantoin, ceftazidime, cefepime, ceftriaxone, ciprofloxacin and amikacin by disc diffusion and MIC assay. Ceftazidime, ampicillin and cephalexin were highly ineffective against several isolates. In order to increase the efficacy of these antibiotics, siderophore mediated Trojan horse strategy was preferred using pyochelin (Pch), a siderophore specific to P. aeruginosa. The Pch was derived from a five step procedure to get an average yield of 94% Pch was tagged to the liposomes with the terminal sulfhydryl (-SH) concentration ranging between 137.5 to 171.2 µmol/mL with a final newline newline newline newlineantibiotic concentration of 1.021 mg/mL. An average size of 87nm and stability (-48 mV to -60 mV) was maintained for the PEGylated liposomal pyochelin encapsulating ceftazidime (PEG-LP-CAZ), cefepime (PEG- LP-CPM) and imipenem (PEG-LP-IPM) respectively. The highly resistant strain PS88 was susceptible on exposure to PEG-LP-CAZ at newline32.04 µg/mL, PEG-LP-CPM at 16.3 ug/mL and PEG-LP-IPM a