Controlling the Evolution of Selective Vancomycin Resistance through Successful Ophthalmic Eye-Drop Preparation of Vancomycin-Loaded Nanoliposomes Using the Active-Loading Method

Abstract

Vancomycin is the front-line defense and drug of choice for the most serious and life-threatening methicillin-resistant Staphylococcus aureus (MRSA) infections. However, poor vancomycin therapeutic practice limits its use, and there is a consequent rise of the threat of vancomycin resistance by complete loss of its antibacterial activity. Nanovesicles as a drug-delivery platform, with their featured capabilities of targeted delivery and cell penetration, are a promising strategy to resolve the shortcomings of vancomycin therapy. However, vancomycin’s physicochemical properties challenge its effective loading. In this study, we used the ammonium sulfate gradient method to enhance vancomycin loading into liposomes. Depending on the pH difference between the extraliposomal vancomycin–Tris buffer solution (pH 9) and the intraliposomal ammonium sulfate solution (pH 5–6), vancomycin was actively and successfully loaded into liposomes (up to 65% entrapment efficiency), while the liposomal size was maintained at 155 nm. Vancomycin-loaded nanoliposomes effectively enhanced the bactericidal effect of vancomycin; the minimum inhibitory concentration (MIC) value for MRSA decreased 4.6-fold. Furthermore, they effectively inhibited and killed heteroresistant vancomycin-intermediate S.aureous (h-VISA) with an MIC of 0.338 μg mL−1. Moreover, MRSA could not develop resistance against vancomycin that was loaded into and delivered by liposomes. Vancomycin-loaded nanoliposomes could be a feasible solution for enhancing vancomycin’s therapeutic use and controlling the emerging vancomycin resistance.

Safety assessment of Enterococcus lactis strains complemented with comparative genomics analysis reveals probiotic and safety characteristics of the entire species

“…The antibiotic susceptibility test was performed following the disc diffusion method [ 24 , 25 ], as described before by Halder and Mandal [ 22 ], using MRS agar and approximately10 8 CFU inoculum from the probiotic strains. The antibiotic discs (Bioanalyse, Turkey) used were Gentamicin (CN: 10-µg/disc), Tetracycline (TE: 30-µg/disc), Chloramphenicol (C: 30-µg/disc), Clindamycin (DA: 2-μg/disc), Erythromycin (E: 15-µg/disc), Kanamycin (K: 30-µg/disc), Streptomycin (S: 10-µg/disc) and Vancomycin (VA: 30-µg/disc).…”

Selection of Excipients for the Preparation of Vancomycin-Loaded Poly(D,L-lactide-co-glycolide) Microparticles with Extended Release by Emulsion Spray Drying

“…DSC studies were performed on the following samples: pure polymer and VAN (Figure 4a), VAN-loaded PLGA microparticles M1-M4 (Figure 4b) and their corresponding physical mixtures containing the same substances as the microparticle formulations (Figure 4c). The baseline shift in the thermogram of the pure VAN compound with a midpoint at 62 °C (Figure 4a) corresponds to a phase transition, which is characteristic of the amorphous drug [30]. Resomer 502H has a Tg value of 44.68 °C.…”

“…DSC studies were performed on the following samples: pure polymer and VAN (Figure 4a), VAN-loaded PLGA microparticles M1-M4 (Figure 4b) and their corresponding physical mixtures containing the same substances as the microparticle formulations (Figure 4c). The baseline shift in the thermogram of the pure VAN compound with a midpoint at 62 • C (Figure 4a) corresponds to a phase transition, which is characteristic of the amorphous drug [30]. Resomer 502H has a Tg value of 44.68 • C. In the DSC thermograms of the microparticles loaded with VAN (Figure 4c) and their physical mixtures (Figure 4d), endothermic events related to the dehydration of vancomycin and the glass transition temperature of the polymer were observed, with no other events detected.…”