Maleimide conjugated PEGylated liposomal antibiotic to combat multi-drug resistant Escherichia coli and Klebsiella pneumoniae with enhanced wound healing potential
Darshan Narendrabhai Ladva, Pradeep Pushparaj Selvadoss, Grishma Kantibhai Chitroda, D. Sivaraman, Jayshree Nellore, Jayakrishna Tippabathani, Sundar Manoharan Solomon
Abstract
Antibiotic resistance is a significant threat, leaving us vulnerable to bacterial infections. Novel strategies are needed to combat bacterial resistance beyond discovering new antibiotics. This research focuses on using maleimide conjugated PEGylated liposomes (Mal-PL-Ab) to individually encapsulate a variety of antibiotics (ceftriaxone, cephalexin, doxycycline, piperacillin, ampicillin, and ceftazidime) and enhance their delivery against multi-drug resistant (MDR) bacteria like Escherichia coli ( E. coli ) and Klebsiella pneumoniae ( K. pneumoniae ). Mal-PL-Ab, with an average size of 84.2 nm ± 4.32 nm, successfully encapsulated these antibiotics with an encapsulation efficiency of 37.73 ± 3.19%. Compared to non-PEGylated liposomes (L-Ab), Mal-PL-Ab exhibited reduced toxicity in human dermal cells, emphasizing the importance of PEGylation in minimizing adverse effects. Mal-PL-Ab significantly decreased the minimum inhibitory concentration (MIC) values against both E. coli and K. pneumoniae by 9.33-fold and eightfold reduction (compared to non-PEGylated liposomes with 2.33-fold and 2.33fold reduction), respectively, indicating enhanced efficacy against MDR strains. Furthermore, in vitro scratch assay and gene expression analysis of human dermal fibroblast revealed that Mal-PL-Ab promoted cell proliferation, migration, and wound healing through upregulation of cell cycle, DNA repair, and angiogenesis-related genes. Harnessing the power of encapsulation, Mal-PL-Ab presents a novel avenue for enhanced antibiotic delivery and wound healing, potentially transcending the limitations of traditional options.