LAUSR

Methicillin-resistant Staphylococcus aureus (MRSA) can cause harmful and potentially deadly infections. Vancomycin remains the first-line antibiotic treatment for MRSA-derived infections. Nevertheless, as a peptide drug, it is poorly absorbed when administered orally due to its high molecular weight and low permeability in the gastrointestinal tract, therefore, administered intravenously for the treatment of systemic diseases. In order to circumvent some of the many drawbacks associated with intravenous injection, other routes of drug delivery should be investigated. One of the strategies which has been employed to enhance transdermal drug delivery is based on microarray patches (MAP). This work, for the first time, describes successful transdermal delivery of vancomycin hydrochloride (VCL) using dissolving and hydrogel-forming MAPs. VCL was formulated into dissolving MAP (DMAP) and reservoirs (film dosage forms, lyophilised wafers and compressed tablets) using excipients, such as poly(vinyl pyrrolidone), poly(vinyl alcohol), sodium hyaluronate, D-sorbitol and glycerol. In this study, hydrogel-forming MAP (HFMAP) were manufactured using aqueous blends containing poly(methylvinyl ether-co-maleic acid) crosslinked by esterification with poly(ethylene glycol). VCL-loaded compressed tablets (60% w/w VCL) were the most promising reservoir to be integrated with HFMAP, based on the physicochemical evaluations performed. Both HFMAP and DMAP successfully delivered VCL in ex vivo studies with the percentage of drug that permeated across neonatal porcine skin recorded at 46.39 ± 8.04% and 7.99 ± 0.98 %, respectively. In in vivo studies, the area under the plasma concentration time curve from time zero to infinity (AUC0-inf) of 162.04 ± 61.84 μg.h/ml and 61.01 ± 28.50 μg.h/ml were achieved following application of HFMAP and DMAP, respectively. In comparison, the AUC0-inf of HFMAP was significantly greater than the oral administration control group which showed AUC0-inf at 30.50 ± 9.18 μg.h/ml (p < 0.05). This work demonstrates that transdermal delivery of VCL is feasible using DMAPs and HFMAPs and could prove effective in the treatment of infectious diseases caused by MRSA, such as skin and soft-tissue infections (SSTIs), lymphatic-related infections and neonatal sepsis.