Evaluation of MDR-specific phage Pɸ-Mi-Pa loaded mucoadhesive electrospun nanofibrous scaffolds against drug-resistant Pseudomonas aeruginosa- induced wound infections in an animal model.

Given the escalating prevalence of drug-resistant wounds, there is a justified imperative to explore innovative and more efficacious therapies that diverge from conventional, ineffective wound healing approaches. This research has introduced a strategy to address multi-drug resistant (MDR) Pseudomonas aeruginosa infections in a chronic wound model, employing MDR-specific phage Pɸ-Mi-Pa loaded onto mucoadhesive electrospun scaffolds. A cocktail of three isolates of P. aeruginosa-specific lytic phages, Pɸ-Mi-Pa 51, Pɸ-Mi-Pa 120, and Pɸ-Mi-Pa 133 were incorporated into varying ratios of fabricated PCL-PVP polymer. These formulations were assessed for their therapeutic efficacy in achieving bacterial clearance in P. aeruginosa-induced wound infections. The study encompassed biological characterization through in vivo wound healing assessments, histology, and histomorphometry. Additionally, morphological, mechanical, and chemical analyses were conducted on the fabricated PCL-PVP electrospun nanofibrous scaffolds. Three clonal differences of the MDR P. aeruginosa-specific phages (Pɸ-Mi-Pa 51, Pɸ-Mi-Pa 120, and Pɸ-Mi-Pa 133) produced lytic activity and were seen to produce distinct and clear zones of inhibition against MDR P. aeruginosa strains Pa 051, Pa 120 and Pa 133 respectively. The average porosity of the nanofibrous scaffolds PB 1, PB 2, PB 3, and PB 4 were 12.2 ± 0.3 %, 22.1 ± 0.7 %, 31.1 ± 2.4 %, 28.0 ± 0.8 % respectively. In vitro cumulative release of MDR-specific phage Pɸ-Mi-Pa from the mucoadhesive electrospun nanofibrous scaffolds was found to be 70.91 % ± 1.02 % after 12 h of incubation after an initial release of 42.8 % ± 3.01 % after 1 h. Results from the in vivo wound healing study revealed a substantial reduction in wound size, with formulations PB 2 and PB 3 exhibiting the most significant reduction in wound size, demonstrating statistically significant results on day 5 (100 % ± 31.4 %). These findings underscore the potential of bacteriophage-loaded electrospun PCL-PVP nanofibrous scaffolds for treating drug-resistant wounds, generating tissue substitutes, and overcoming certain limitations associated with conventional wound care matrices.

Encapsulation of Andrographolide in poly(lactide-co-glycolide) Nanoparticles: Formulation Optimization and in vitro Efficacy Studies.

Andrographolide is a potential chemopreventive and chemotherapeutic agent that suffers from poor aqueous solubility. Encapsulation in poly(lactide-co-glycolide) (PLGA) nanoparticles can overcome solubility issues and enable sustained release of the drug, resulting in improved therapeutic efficacy. In this study, andrographolide was encapsulated in PLGA nanoparticles via emulsion solvent evaporation technique. Effect of various formulation parameters including polymer composition, polymer molecular weight, polymer to drug ratio, surfactant concentration and the organic solvent used on nanoparticle properties were investigated. A selected formulation was used to determine the effect of encapsulation in nanoparticles on andrographolide's in vitro anticancer efficacy. Nanoparticles formulated using a polymer with 85:15 lactide to glycolide ratio and ethyl acetate as the organic solvent were found to be optimal based on average hydrodynamic particle size (135 ± 4 nm) and drug loading (2.6 ± 0.6%w/w). This formulation demonstrated sustained release of andrographolide over 48 h and demonstrated significantly greater in vitro anticancer efficacy compared to free drug in a metastatic breast cancer cell line. These results suggest that additional, more in-depth efficacy studies are warranted for the nanoparticle formulation of andrographolide.