Chitosan-carrageenan microbeads containing nano-encapsulated curcumin: Nano-in-micro hydrogels as alternative-therapeutics for resistant pathogens associated with chronic wounds.

Antimicrobial resistance is an issue of global relevance for the treatment of chronic wound infections. In this study, nano-in-micro hydrogels (microbeads) of chitosan and κ-carrageenan (CCMBs) containing curcumin-loaded rhamnosomes (Cur-R) were developed. The potential of Cur-R-CCMBs for improving the antibacterial activity and sustained release of curcumin was evaluated. Curcumin-loaded rhamnosomes (rhamnolipids functionalized liposomes) had a mean particle size of 116 ± 7 nm and a surface-charge of -24.5 ± 9.4 mV. The encapsulation efficiency of curcumin increased from 42.83 % ± 0.69 % in Cur-R to 95.24 % ± 3.61 % respectively after their embedding in CCMBs. SEM revealed smooth surface morphology of Cur-R-CCMBs. FTIR spectroscopy confirmed the presence of weak electrostatic and hydrophobic interactions among curcumin, rhamnosomes, and microbeads. Cur-R-CCMBs had demonstrated significant antibacterial activity against multi-drug resistant chronic wound pathogens including Staphylococcus aureus and Pseudomonas aeruginosa. Cur-R-CCMBs also exhibited significantly higher anti-oxidant (76.85 % ± 2.12 %) and anti-inflammatory activity (91.94 % ± 0.41 %) as well as hemocompatibility (4.024 % ± 0.59 %) as compared to pristine microbeads. In vivo infection model of mice revealed significant reduction in the viable bacterial count of S. aureus (∼2.5 log CFU/mL) and P. aeruginosa (∼2 log CFU/mL) for Cur-R-CCMBs after 5 days. Therefore, nano-in-micro hydrogels can improve the overall efficacy of hydrophobic antimicrobials to develop effective alternative-therapeutics against resistant-pathogens associated with chronic wound infections.