Nano-active carboxymethyl cellulose hydrogels infused with sodium deoxycholate functionalized permeosomes to combat biofilm producing resistant pathogens associated with chronic wounds

Abstract

During the past decade, the incidence of chronic wounds has continued to rise due to the growing threat of multidrug-resistant (MDR) biofilm-producing bacteria residing inside the convoluted architecture of skin. Herein, we have developed sodium deoxycholate functionalized liposomes (nano-permeosomes) loaded with tea tree oil (TTO) infused inside carboxymethyl cellulose hydrogels (CMC-TTO-LP). Nano-permeosomes exhibited high encapsulation efficiency of TTO (91 % ± 0.36 %). SEM revealed the smooth and ultra-deformable morphology of nano-permeosomes. Nano-permeosomes exhibited an average size of 178.5 ± 6.42 nm with a zeta potential of -53.2 ± 7.03 mV. FTIR spectroscopy confirmed the presence of weak electrostatic interactions, including hydrophobic forces, among nano-permeosomes, TTO, and hydrogels. CMC-TTO-LP exhibited significant antibacterial and antibiofilm activity against MDR Pseudomonas aeruginosa and Staphylococcus aureus. CMC-TTO-LP exhibited high antioxidant activity (68 % ± 2.8 %), hemocompatibility, and cytocompatibility. Nano-permeosomes prevented the burst release and allowed sustained release kinetics of TTO from CMC-TTO-LP. Moreover, under ex vivo conditions, nano-active hydrogels exhibited high apparent permeability, average flux (42.9 ± 2.42 μL/cm²/h), and skin retention (24.94 ± 0.45 μL/cm²) of TTO across the dermal barrier of rabbit skin. Hence, these advanced nano-active hydrogels (CMC-TTO-LP) can potentially deliver TTO via the transdermal route and act as an appealing candidate in controlling chronic wound infections persisting due to MDR pathogens.

Keywords: Antimicrobial resistance; Bile salt; Carboxymethyl cellulose; Chronic wounds; Ex-vivo; Transdermal delivery.