title: Targeted delivery of a poorly water-soluble compound to hair follicles using polymeric nanoparticle suspensions.
abstract: 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.
authors: Bend Research Inc., Bend, OR 97701, USA.
authors: Michael
authors: M
authors: Morgen
authors: Guang Wei
authors: GW
authors: Lu
authors: Daniel
authors: D
authors: Du
authors: Randall
authors: R
authors: Stehle
authors: Franz
authors: F
authors: Lembke
authors: Jessica
authors: J
authors: Cervantes
authors: Susan
authors: S
authors: Ciotti
authors: Roy
authors: R
authors: Haskell
authors: Dan
authors: D
authors: Smithey
authors: Kevin
authors: K
authors: Haley
authors: Conglin
authors: C
authors: Fan
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001578:Benzopyrans / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D006224:Cricetinae; D004339:Drug Compounding / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D018859:Hair Follicle / Q000187:drug effects*; D051379:Mice; D008809:Mice, Inbred C3H; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D011817:Rabbits; D012627:Sebaceous Glands / Q000187:drug effects; D012995:Solubility; D013450:Sulfones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013535:Suspensions / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D001578:Benzopyrans; D011108:Polymers; D013450:Sulfones; D013535:Suspensions; C420110:UK 157147; C013517:ethyl cellulose; D002482:Cellulose