Antibiofilm Effects of Macrolide Loaded Microneedle Patches: Prospects in Healing Infected Wounds.

AIM: The aim of this study was to fabricate polymeric microneedles, loaded with macrolides (erythromycin, azithromycin), using hyaluronic acid and polyvinyl pyrollidone. METHODS: These microneedles were fabricated using a vacuum micromolding technique. The integrity of the microneedle patches was studied by recording their morphologic features, folding endurance, swelling and micro-piercing. Physicochemical characteristics were studied by differential scanning calorimetry, thermogravimetric analysis and fourier transform infrared spectroscopy. In-vitro drug release, antibiofilm and effect of microneedle patch on wound healing were also studied to confirm the efficacy of the formulations. RESULTS: Formulated patches displayed acceptable folding endurance (>100) and uniform distribution of microneedles (10 × 10) that can penetrate parafilm. Differential scanning calorimetry results depict a decrease in the crystallinity of macrolides following their incorporation in to a polymer matrix. Percentage release of azithromycin and erythromycin from the polymeric patch formulations (over 30 min) was 90% and 63% respectively. Broadly, the zone of bacterial growth inhibition follows the same order for Staphylococcus aureus, Escherichia coli and Salmonella enterica. After 5 days of treatment with azithromycin patches, the wound healing was complete and skin structure (e.g. hair follicles and dermis) was regenerated. CONCLUSION: It was concluded that azithromycin loaded microneedle patches can be used to treat biofilms in the infected wounds.

Fabrication and characterisation of self-applicating heparin sodium microneedle patches.

The aim of this study was to develop heparin sodium loaded microneedle patches using different compositions of polyvinyl alcohol polymer and sorbitol. A vacuum micromolding technique was used to fabricate microneedle patches while heparin sodium was loaded into needle tips. Physical features of patches were evaluated by measuring thickness, width, folding endurance and swelling percentage. Patches were also characterised by optical microscopy and scanning electron microscopy to determine the microneedle length and surface morphologies. A preliminary assessment of the microneedle performance was studied by examining the in-vitro insertion to the parafilm and recording the in-vitro drug release profile. In-vivo activity of patches was confirmed by measuring activated partial thromboplastin time and histological examination of the micropierced skin tissues. Prepared patches were clear, smooth; uniform in appearance; with sharp pointed microprojections and remained intact after 1000 folding. The microneedles were stiffer in nature, as they reproduce microcavities in the parafilm membrane following hand pushing without any structural loss. Insertion study results showed successful insertion of microneedles into the parafilm. Disrupted stratum corneum evident from histological examination confirmed successful insertion of the microneedle without affecting the vasculature. In-vitro release study confirmed ∼92% release of the loaded drug within 120 min. A significant prolongation of activated partial thromboplastin time (4 folds as compared to negative control) was recorded following the application of heparin sodium loaded microneedle patch onto rabbit skin. In conclusion microneedles are a valuable drug delivery system, benefiting the patients with minimal skin invasion and also allowing self-administration of heparin sodium in a sustained release manner for the management of chronic ailments.