Chloramphenicol encapsulated in poly-ε-caprolactone–pluronic composite: nanoparticles for treatment of MRSA-infected burn wounds

Abstract

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) infection has increased precipitously over the past several decades, with far-reaching health care and societal costs. MRSA infections in the context of burn wounds lead to invasive disease that could potentially cause mortality. Chloramphenicol is a well-known broad-spectrum bacteriostatic antibiotic that has been used since 1949, but due to its hydrophobicity, poor penetration in skin, fast degradation, and toxicity, its application has been hindered. Furthermore, it has been demonstrated that old antibiotics such as chloramphenicol remained active against a large number of currently prevalent resistant bacterial isolates due to their low-level use in the past. Recently, the novel nanoparticulate drug-delivery system has been used and reported to be exceptionally useful for topical therapeutics, due to its distinctive physical characteristics such as a high surface-to-volume ratio and minuscule size. It helps to achieve better hydrophilicity, bioavailability, and controlled delivery with enhanced therapeutic index, which has resulted in decreased toxicity levels compared to the crude drug. Here, we report a novel chloramphenicol loaded with poly(ε-caprolactone) (PCL)-pluronic composite nanoparticles (CAM-PCL-P NPs), physicochemical characterizations, and its bioactivity evaluation in a MRSA-infected burn-wound animal model. CAM-PCL-P NPs could encapsulate 98.3% of the drug in the nanoparticles and release 81% of the encapsulated drug over 36 days with a time to 50% drug release of 72 hours (51%). Nanoparticle suspensions maintained the initial properties with respect to size and encapsulation efficiency, even after 6 months of storage at 4°C and 25°C, respectively ( P >0.05). Significant reduction in the level of toxicity was observed for CAM-PCL-P NPs compared with that of free drug as confirmed from hemolytic activity against human blood erythrocytes and cytotoxicity assay against an MCF-7 breast cancer cell line. In vitro antibacterial activities were performed by zone of inhibition, minimum inhibitory concentrations, minimum bacterial concentration, and time-kill assays, which showed that CAM-PCL-P NPs exhibited significantly enhanced anti-MRSA activity against ten clinical isolates of MRSA strains. The augmented activity of CAM-PCL-P NPs was further tested on a MRSA-infected burn-wound animal model and achieved quicker efficacy in MRSA clearance and improved the survival rate compared with free-chloramphenicol treatment. Thus, we propose CAM-PCL-P NPs as a promising novel antimicrobial candidate that may have a good potential for preclinical applications.

Antifungal potential of some collagen-based nanocomposites Against Candida lusitaniae

“…If we compare effectiveness of the test nanomaterials, it can be concluded that the most effective against C. lusitaniaе was Chloramphenicol in the nutrient medium in combination withhold: RGO (2:1) followed by Coll: Ag/ SiO 2 /RGO (2:1)>Coll: ZnTiO3 (2:1)>Coll: Ag/ZnO/ZnTiO 3 (2:0.8)>Coll: Ag/RGO (2:0.7). Our results are comparable with these previously reported by other authors [61,62,63,64]. Strongest effect of Coll: Ag/ SiO 2 /RGO nanocomposite without antibiotic in nutrient medium was possibly due to the role of SiO 2 as dispersing agent (vehiculum).…”

Surface-functionalized cockle shell–based calcium carbonate aragonite polymorph as a drug nanocarrier

“…Furthermore, these comparable patterns of XRD patterns also demonstrate that the drug molecule was loaded within the nanocarriers. Similar patterns of findings were also observed by other studies 8,21,56,57…”

Protective Effect of Bioactivity Guided Fractions of Ziziphus jujuba Mill. Root Bark against Hepatic Injury and Chronic Inflammation via Inhibiting Inflammatory Markers and Oxidative Stress

“…Tetrazolium salt assay (MTT) was used to determine the cytotoxic concentration of ZJME and ZJWF (Kalita S. et al, 2015, 2016; Kandimalla et al, 2016b; Konwar et al, 2016). Briefly, the cells from the culture flask were trypsinized and seeded in 96-well plate at 5 × 10 3 cells/well in a culture medium and incubated in the CO 2 incubator at 37°C for 24 h. Then the culture medium from the wells was replaced with new media and ZJME and ZJWF at different concentrations (5, 25, 50,125, 250, and 500 μg/mL).…”