Targeted delivery of a poorly water-soluble compound to hair follicles using polymeric nanoparticle suspensions.

This study explored the utility of topically applied polymeric nanoparticle suspensions to target delivery of poorly water-soluble drugs to hair follicles. Several formulations of amorphous drug/polymer nanoparticles were prepared from ethyl cellulose and UK-157,147 (systematic name (3S,4R)-[6-(3-hydroxyphenyl)sulfonyl]-2,2,3-trimethyl-4-(2-methyl-3-oxo-2,3-dihydropyridazin-6-yloxy)-3-chromanol), a potassium channel opener, using sodium glycocholate (NaGC) as a surface stabilizer. Nanoparticle suspensions were evaluated to determine if targeted drug delivery to sebaceous glands and hair follicles could be achieved. In in vitro testing with rabbit ear tissue, delivery of UK-157,147 to the follicles was demonstrated with limited distribution to the surrounding dermis. Delivery to hair follicles was also demonstrated in vivo, based on stimulation of hair growth in tests of 100-nm nanoparticles with a C3H mouse model. The nanoparticles were well-tolerated, with no visible skin irritation. In vivo tests of smaller nanoparticles with a hamster ear model also indicated targeted delivery to sebaceous glands. The nanoparticles released drug rapidly in in vitro nonsink dissolution tests and were stable in suspension for 3 months. The present results show selective drug delivery to the follicle by follicular transport of nanoparticles and rapid release of a poorly water-soluble drug. Thus, nanoparticles represent a promising approach for targeted topical delivery of low-solubility compounds to hair follicles.

Rapid determination of trace amounts of minoxidil in hamster skin follicles with various formulations using narrow-bore LC/EC.

A sensitive liquid chromatographic method with electrochemistry (LC/EC) was developed for the determination of trace of minoxidil in hamster skin follicles after topical administration of the ear using various formulations. The minoxidil in the sebaceous glands of the hamster ear was isolated from the skin and the follicles in different skin layers were treated with aqueous trichloroacetic acid followed by acetonitrile. The supernatant was directly injected into the LC/EC system and minoxidil was detected by oxidation at +800 mV versus Ag/AgCl using a glassy carbon electrode. The analytical recoveries were between 94.4 and 103.1% and the linearity was excellent up to 250 microg/ml with a regression coefficient (r(2)) of 0.9988. The LC/EC and the widely used radiolabeled scintillation methods agree well and both show high sensitivities. The LC/EC method is rapid and cost-effective with a detection limit of only 1 ng/ml.