Curcumin Nanoparticles Improved Diabetic Wounds Infected With Methicillin-Resistant Staphylococcus aureus Sensitized With HAMLET

Abstract

Accurately orchestrated course of events normally observed in healing are not followed in diabetic wounds, and bacterial colonization/infection further messes up the process. Novel therapeutic options for treatment of infections caused by multidrug-resistant Staphylococcus aureus are urgently needed. HAMLET (human α-lactalbumin made lethal to tumor cells) has been reported to be able to sensitize bacterial pathogens to traditional antimicrobial agents. The aim was to assess the wound healing activity of curcumin nanoparticles in diabetic wounds infected with methicillin-resistant Staphylococcus aureus (MRSA) sensitized with HAMLET. Fifty male rats were randomized into 5 groups of 10 animals each. In CONTROL group, 0.1-mL sterile saline 0.9% solution was added to the wounds with no infection. In MRSA group, the wounds were infected with MRSA and only treated with 0.1-mL sterile saline 0.9% solution. In MRSA/HAMLET group, infected wounds were treated with HAMLET (100 µg). In MRSA/CNP group, animals with infected wounds were treated with 0.1 mL topical application of 1 mg/mL curcumin nanoparticles. In MRSA/CNP/HAMLET group, animals with infected wounds were treated with topical application of 0.1 mL solution of curcumin nanoparticles (1 mg/mL) and HAMLET (100 µg). All test formulations were applied for 10 days, twice a day, starting from first treatment. Microbiological examination; planimetric, biochemical, histological, and quantitative morphometric studies; immunohistochemical staining for angiogenesis; determination of hydroxyproline levels; and reverse transcription polymerase chain reaction for caspase 3, Bcl-2, and p53 showed that there was significant difference between animals in MRSA/CNP/HAMLET group compared with other groups ( P < .05). Curcumin nanoparticles improved diabetic wounds infected with MRSA sensitized with HAMLET and had the potential to offer more attention to this safer agent for topical use in infected diabetic wounds.

Accelerative Effect of Cinnamon Nanoparticles as well as HAMLET on Healing of Wounds Infected with MRSA in Diabetic Rats

“…We followed the methods of others to prepare the HAMLET [ 16 ]. In this method, ethylenediaminetetraacetic acid- (EDTA-) treated, partially unfolded α -lactalbumin as well as oleic acid (C18:1) on an anion exchange matrix was converted to a stable protein-lipid combination.…”

“…We followed the methods of others to develop diabetes [ 16 ]. Accordingly, the rats underwent fasting for one night.…”

“…We followed the methods of others to develop wounds and infection [ 16 ]. To anesthetize the animals, they received combination of 70 mg/kg ketamine and 5 mg/kg xylazine intraperitoneally.…”

“…We followed the methods of others for microbiological tests [ 16 ]. We aseptically excised the granulated tissues 7 and 14 days after wound creation to get the total bacterial count.…”

“…We followed the methods of others for planimetric studies in the excisional wound model [ 16 ]. In brief, the process of healing was investigated via measurement of reduction in the wound surface; therefore, we put a ruler as a scale next to the wounds, and with a digital camera immediately after wounding and on days 6, 9, 12, 15, 18, and 21, photographs were taken.…”