RESUMEN
Background: Scar is an unpleasant skin lesion that occurs following deep wounds or burns. The application of local triamcinolone is a common treatment for scar treatment and prevention, which should be repeated several times in conventional dosage forms. An effort has been made here to provide a prolonged triamcinolone dermal delivery by microneedle technology, which can also be used for wound closure. Objectives: This study aimed to develop a long-lasting polylactic acid (PLA) microneedle patch for the prolonged release of triamcinolone acetonide (TrA) that could potentially be used for closure of wound edges and scar prevention and treatment. Methods: In this study, 3% and 10% TrA-containing polymeric microneedles were fabricated using the micro molding-solvent casting method. Optical microscopy, X-ray diffraction analysis (XRD), Fourier-transform infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC) were used for the characterization of microneedles. Mechanical strength was evaluated using a compression test and methylene blue staining. Additionally, the insertion depth was determined by histopathological sectioning of human skin samples and also insertion into Parafilm®M as a skin model. The in vitro drug release profile of the microneedles was studied over 34 days, and the kinetic model was determined. The ex-vivo skin permeation of TrA was studied using a Franz-diffusion cell. Results: The TrA-containing PLA microneedles were fabricated with a uniform structure without any failure, deterioration, or loss of needles. Fourier-transform infrared spectroscopy and differential scanning calorimetry showed no interaction between TrA and PLA, and no effect on crystallinity and thermal behavior of TrA on polymer was detected. Microneedles showed appropriate mechanical properties, which were able to penetrate to about 900 - 1000 µm depth. Release profile from the whole body of 10% and 3% microneedle fitted to Higuchi model with cumulative amounts of 625 µg and 201.64 µg over 34 days. Release from the needles followed zero-order kinetic with cumulative amounts of 30.04 µg and 20.36 µg for 10% and 3%, respectively, for 34 days. Permeation was calculated to be 17 µg/day for 10% TrA-containing microneedle. Conclusions: The results suggested that suitable PLA microneedles containing TrA with prolonged release behavior can be successfully constructed with the solvent casting method.
RESUMEN
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.
Asunto(s)
Materiales Biocompatibles , Biomimética , Animales , Biopolímeros , Sistemas de Liberación de Medicamentos , AgujasRESUMEN
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.