Temperature-Enhanced Follicular Penetration of Thermoresponsive Nanogels

Hair follicles can serve as an effective reservoir for dermal drug delivery upon the topical application of particulate substances. Here, the follicular penetration of an indodicarbocyanine-labelled thermoresponsive nanogel (189 nm) having a cloud point temperature of 34 degrees C and linked via an acid-labile linker to the model drug indocarbocyanine was investigated. In total, 227 hair follicles of porcine ear skin were examined after topical application of the thermoresponsive nanogels at room temperature (21 degrees C), physiological skin surface temperature (32 degrees C) and core body temperature (37 degrees C) for the follicular penetration depths of indodicarbocyanine and indocarbocyanine using confocal laser scanning microscopy. The results showed a significantly increased mean follicular penetration of the carrier to a depth of 298.8 +/- 85.8 mu m after incubation at 37 degrees C compared to samples incubated at 21 degrees C and 32 degrees C with mean follicular penetration depths of 202.7 +/- 81.7 mu m and 219.4 +/- 52.9 mu m, respectively (p < 0.001). Possibly structural changes in the thermoresponsive nanogel induced by the increased incubation temperature led to an enhancement of follicular penetration. Therefore, thermoresponsive nanogels may be suitable for the temperature- enhanced penetration into the hair follicles under physiological conditions.