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.

Chitosan hydrogel for topical delivery of ebastine loaded solid lipid nanoparticles for alleviation of allergic contact dermatitis.

Ebastine, is an antihistamine drug that exerts its effect upon oral administration in humans for the treatment of allergic contact dermatitis (ACD), it also has some systemic side effects like gastric distress, headache, drowsiness, and epistaxis. Moreover, topical corticosteroids are used for treatment of ACD, which causes the human skin to lose its thickness and elasticity. Hence, ebastine-loaded solid lipid nanoparticles (E-SLNs) were prepared and their topical efficacy against allergic contact dermatitis was determined. Compritol 888 ATO and tween 80 were used to prepare E-SLNs by cold dilution of the hot micro-emulsion. E-SLNs were optimized statistically by employing a central composite design using Design-Expert® version 11.0. Optimized E-SLNs showed spherical surface morphology, zeta potential of -15.6 ± 2.4 mV, PDI of 0.256 ± 0.03, and particle sizes of 155.2 ± 1.5 nm and th eentrapment efficiency of ebastine was more than 78%. Nanoparticles were characterized using FT-IR, XRD, and TEM. An E-SLNs loaded hydrogel was prepared using chitosan as a gelling agent and glutaraldehyde as a crosslinker. In vitro drug release studies performed for 24 hours on the E-SLNs dispersion and E-SLNs loaded hydrogel showed a sustained release of maximum 82.9% and 73.7% respectively. In vivo studies were conducted on BALB/c mice to evaluate the topical efficacy of the E-SLNs loaded hydrogel for allergic contact dermatitis. ACD was induced on the ear using picryl chloride solution. After induction, ears were treated daily with the E-SLNs loaded hydrogel for 15 days. Swelling behavior, mast cell count, and histopathological studies of the ear confirmed that the hydrogel alleviated the symptoms of allergic contact dermatitis.