Microneedles assisted controlled and improved transdermal delivery of high molecular drugs via in situ forming depot thermoresponsive poloxamers gels in skin microchannels
Skin is considered as an attractive route for variety of drug molecule administration. However, it is proved to be the main physical barrier for drug flux owing to their poor permeability and low bioavailability across stratum corneum layer. In the current study, novel approach has been used to enhance transdermal delivery via microporation through combination of poloxamers gels and microneedles (MNs) arrays. The phase transition of poloxamers at various concentrations from sol–gel was evaluated using AR2000 rheometer to confirm MNs-assisted in situ forming depots. Temperature test confirmed gelation between 32 and 37 °C. Curcumin was loaded in poloxamer formulations at variable concentrations and its effect showed reduction in critical gelation temperature (CGT) owing to its hydrophobic nature. Microneedle arrays (600 µm) prepared from Gantrez S-97, PEG10000 and gelatin B using (19 × 19) laser-engineered silicone micromoulds showed high mechanical stability investigated via Texture analyzer. From in situ dissolution profile, gelatin 15% w/w based MNs displayed quicker dissolution rate in comparison to PG10000. VivoSight® OCT scanner and dye tracking confirmed that PG10000 MNs arrays pierced SC layer, infiltrate the epidermis and goes to dermis layer. From in vitro permeation, it was concluded that 20% w/w PF127® gel formulations containing (0.1% and 0.3%) curcumin displayed high curcumin permeation for comparatively longer time through microporated skin samples in comparison to non-microporated skin. The curcumin distribution in skin tissues with higher florescence intensity was noted in MNs treated skin samples by confocal microscopy. FTIR confirmed the structure formation of fabricated MNs, while TGA showed dry, brittle and rigid nature of gelatin MNs.