Fabrication of controlled-release silver nanoparticle polylactic acid microneedles with long-lasting antibacterial activity using a micro-molding solvent-casting technique.

Abstract

Most topical drug delivery techniques do not provide therapeutic concentrations for treatment of surgical site and other local infections and, therefore, require some kind of enhancement, such as physical methods like microneedles, the subject of the present investigation. Here, controlled-release long-lasting antibacterial polylactic acid (PLA) microneedles containing 1, 3, and 5% silver nanoparticles (AgNP) were prepared using micro-molding solvent-casting technique. Microneedles were characterized using optical microscopy, SEM, FTIR, XRD, and DSC. Also, mechanical strength, barrier disruption ability, insertion depth, in-vitro release kinetics, antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa, and silver permeation through rat skin were studied. Microneedles showed good mechanical strength with no signs of failure at an optimum PLA concentration of 25%(w/v). FTIR revealed no chemical interaction between ingredients, and XRD confirmed presence of AgNP in microneedles. Microneedles penetrated the skin model at depth of up to 1143μm resulting 5-7 times increase in transepidermal water loss (TEWL). Release studies showed 2.2, 6.8, and 8.1µg silver release from the whole body (obeying Higuchi's release model) and 0.33, 0.45, and 0.78µg from the needles alone (obeying Fickian-cylindrical type release) for 1, 3, and 5% AgNP microneedles, respectively. Also, prolonged antibacterial activity (for 34days) was observed. Skin studies over 72h indicated that besides needles, silver is also released from the baseplate which had a marginal share in total silver permeation through the skin. In conclusion, a straightforward solvent-casting technique can be used to successfully prepare strong AgNP-containing PLA microneedles capable of long-lasting antibacterial activity.