Fabrication and development of controlled release PLGA microneedles for macromolecular delivery using FITC-Dextran as model molecule

Abstract

The use of biodegradable polymers has been prominent in the field of drug delivery due to its degradability and biocompatible properties. These polymers when used to prepare microneedles, impart high mechanical strength, sustained drug release profile, and long term biocompatibility. In this study, PLGA (poly (D, L-lactic co-glycolic acid)) and PVA (Polyvinyl Alcohol) were used in combination to optimize the microneedle fabrication for high molecular weight FITC Dextran (4 kDa MW) to be used as a model drug. FITC-Dextran loaded PLGA microneedles were fabricated using a mold casting technique. MNs were characterized for the textural properties, FITC-Dextran release profile, and in-vitro permeation profile. The fate of microneedles in the skin (ex vivo) was characterized using fluorescence and confocal imaging. The FITC -Dextran MNs (10 × 10 array) had a dimension of 415 ± 2.65 μm height, 207 ± 1.63 μm width of the base and a needle pitch of 463 ± 1.45 μm. The texture analysis data showed puncture force for FITC-Dextran loaded PLGA microneedles (28.46 ± 0.23 g) and PLGA microneedles (16.92 ± 0.04 g). The Cumulative permeation of FITC-Dextran after 48 h was 2.34 ± 0.40 μg/cm2 and it showed a 31 fold higher permeation profile than its respective control. Ex vivo imaging studies were used to characterize the fluorescence intensity of FITC-Dextran in the skin. This study demonstrates that incorporating higher molecular weight molecules into PLGA microneedles proved to be an effective strategy to sustain the release of macromolecules across stratum corneum/epidermis for transdermal delivery.