Protein-based microneedles for biomedical applications: A systematic review.

Microneedles are minimally-invasive devices with the unique capability of bypassing physiological barriers. Hence, they are widely used for different applications from drug/vaccine delivery to diagnosis and cosmetic fields. Recently, natural biopolymers (particularly carbohydrates and proteins) have garnered attention as safe and biocompatible materials with tailorable features for microneedle construction. Several review articles have dealt with carbohydrate-based microneedles. This review aims to highlight the less-noticed role of proteins through a systematic search strategy based on the PRISMA guideline from international databases of PubMed, Science Direct, Scopus, and Google Scholar. Original English articles with the keyword "microneedle(s)" in their titles along with at least one of the keywords "biopolymers, silk, gelatin, collagen, zein, keratin, fish-scale, mussel, and suckerin" were collected and those in which the proteins undertook a structural role were screened. Then, we focused on the structures and applications of protein-based microneedles. Also, the unique features of some protein biopolymers that make them ideal for microneedle construction (e.g., excellent mechanical strength, self-adhesion, and self-assembly), as well as the challenges associated with them were reviewed. Altogether, the proteins identified so far seem not only promising for the fabrication of "better" microneedles in the future but also inspiring for designing biomimetic structural biopolymers with ideal characteristics.

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

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 1143 µm resulting 5-7 times increase in transepidermal water loss (TEWL). Release studies showed 2.2, 6.8, and 8.1 µg silver release from the whole body (obeying Higuchi's release model) and 0.33, 0.45, and 0.78 µg from the needles alone (obeying Fickian-cylindrical type release) for 1, 3, and 5% AgNP microneedles, respectively. Also, prolonged antibacterial activity (for 34 days) was observed. Skin studies over 72 h 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.