Effect of gelatin nanoparticles’ size and charge on iontophoretic targeted deposition to the hair follicles

Hair follicles (HFs) represent a route of interest to drug delivery for treating several skin conditions. Iontophoresis, on the other hand, is a physical method to enhance drug permeation by applying a low electrical current to the formulation. HFs can be targeted following topical iontophoretic application, as they represent a pathway of lower electrical resistance, as well as a drug reservoir, in particular useful for nanoparticles (NPs), which can preferably accumulate in these structures. Combining both strategies may provide optimal results, but the literature still lacks evidence of the ideal NP characteristics for the iontophoretic drug delivery targeting the HFs. Here, we aimed to evaluate the effect of gelatin NPs’ size and charge under iontophoresis application on NPs’ deposition into the HFs. Four gelatin NP formulations were produced with varying gelatin concentrations and gelatin types (positively charged type A and negatively charged type B), with sizes ranging from 220 to 770 nm. A fluorescent dye, TRITC-dextran 150 kDa, was encapsulated for monitoring NPs deposition. Cutaneous penetration experiments were performed in vitro with and without iontophoresis for 6 h with pig ear skin. The deposition profile was assessed by confocal laser scanning microscopy. Photomicrographs showed a higher accumulation of the larger positively charged NPs (AL), reaching deeper portions of HFs, and showed iontophoresis further increased their deposition, resulting in the highest signal. In conclusion, these findings shed light on the applications of NPs and bring novel treatment opportunities for several diseases compromising the hair follicles.