Dendritic polyglycerol and N-isopropylacrylamide based thermoresponsive nanogels as smart carriers for controlled delivery of drugs through the hair follicle

Nanoparticles with a size of several hundred nanometers can effectively penetrate into the hair follicles and may serve as depots for controlled drug delivery. However, they can neither overcome the hair follicle barrier to reach the viable cells nor release the loaded drug adequately. On the other hand, small drug molecules cannot penetrate deep into the hair follicles. Thus, the most efficient way for drug delivery through the follicular route is to employ nanoparticles that can release the drug close to the target structure upon exposure to some external or internal stimuli. Accordingly, 100-700 nm sized thermoresponsive nanogels with a phase transition temperature of 32-37 degrees C were synthesized by the precipitation polymerization technique using N-isopropylacrylamide as a monomer, acrylated dendritic polyglycerol as a crosslinker, VA-044 as an initiator, and sodium dodecyl sulphate as a stabilizer. The follicular penetration of the indodicarbocyanine (IDCC) labeled nanogels into the hair follicles and the release of coumarin 6, which was loaded as a model drug, in the hair follicles were assessed ex vivo using porcine ear skin. Confocal laser scanning microscopy (CLSM) enabled independent tracking of the nanogels and the loaded dye, although it is not as precise and accurate as standard analytical methods. The results showed that, unlike smaller nanogels (<100 nm), medium and larger sized nanogels (300-500 nm) penetrated effectively into the hair follicles with penetration depths proportional to the nanogel size. The release of the loaded dye in the hair follicles increased significantly when the investigation on penetration was carried out above the cloud point temperature of the nanogels. The follicular penetration of the nanogels from the colloidal dispersion and a 2.5% hydroxyethyl cellulose gel was not significantly different.