Purpose: Microneedles as a transdermal delivery platform have gained lot of pharmaceutical importance in the recent times. Although, biodegradable microneedles (MN) and nanoparticles loaded MN have proven its potential there is still a need for an in-depth characterization and its fate onto skin on application pertaining to its topical distribution, extent of penetration, mechanism, dissolution, safety and biodegradation. In view to understand these mechanisms, the objective of this study was to observe the topical distribution profile, fate and penetration of needle and drug distribution of microneedles in skin.
Methods: To study the fate of microneedles in vivo, two set of microneedles were chosen for the study. FITC loaded microneedles as a representative hydrophilic molecule and Nile Red representing lipophilic molecule in Solid lipid nanoparticle (SLN) through microneedles were chosen which also assisted in visualization. Microneedles were inserted into rat skin at predetermined time intervals (0h, 0.25 h, 0.5h, 1h, 2h and 4h). Skin resealing kinetics was measured using a TEWL (Trans epidermal water loss) meter -Tewameter®. At the end of each time point the rat skin was isolated for imaging studies. On isolation, rat skin was observed for topical distribution under fluorescence microscope. Next, the skin was subjected to cryo-sectioning to study the penetration profile of each molecule.
Results: The skin resealing kinetics performed on the rats showed that the pore size of punctured site decreased within 1h which was supported by the decrease in TEWL value. At the end of 4h, the skin epidermis appeared to be completely sealed. Observance of the isolated rat skin for topical distribution showed distinct results for the two molecules chosen. The maximum distribution of FITC was observed at 30 min, after which the FITC intensity gradually decreased. Nile Red SLN intensity increased with time which could be attributed to the controlled release profile of SLNs. Histological staining of microneedles attributed to the depth of microneedle penetration.
Conclusion: With our limited studies, we observed that in vivo imaging is crucial in understanding the fate of drug distribution through microneedles as well as solid lipid nanoparticle delivery through microneedles. We found that the fate of Nile red loaded solid lipid nanoparticle had an increased distribution intensity with time, whereas FITC loaded microneedles drug distribution declined with time. This predicts the fate of hydrophilic and lipophilic molecule and opens the wide potential of MN in drug delivery. We found that the resealing of the epidermis was within the acceptance levels of irritancy thus overcoming the safety concerns. Overall results revealed that in vivo imaging should be used as a potential tool to evaluate microneedle-based devices.