Enhanced topical delivery of finasteride using glyceryl monooleate-based liquid crystalline nanoparticles stabilized by cremophor surfactants.
The aim of this study was to investigate the capability of two surfactants, Cremophor RH 40 (RH) and Cremophor EL (EL), to prepare liquid crystalline nanoparticles (LCN) and to study its influence on the topical delivery of finasteride (FNS). FNS-loaded LCN was formulated with the two surfactants and characterized for size distribution, morphology, entrapment efficiency, in vitro drug release, and skin permeation/retention. Influence of FNS-loaded LCN on the conformational changes on porcine skin was also studied using attenuated total reflectance Fourier-transform infrared spectroscopy. Transmission electron microscopical image confirmed the formation of LCN. The average particle size of formulations was in the range of 165.1-208.6 and 153.7-243.0 nm, respectively. The formulations prepared with higher surfactant concentrations showed faster release and significantly increased skin permeation. Specifically, LCN prepared with RH 2.5% presented higher permeation flux (0.100 ± 0.005 μgcm(-2)h(-1)) compared with lower concentration (0.029 ± 0.007 μgcm(-2)h(-1)). Typical spectral bands of lipid matrix of porcine skin were shifted to higher wavenumber, indicating increased degree of disorder of the lipid acyl chains which might cause fluidity increase of stratum corneum. Taken together, Cremophor surfactants exhibited a promising potential to stabilize the LCN and significantly augmented the skin permeation of FNS.
College of Pharmacy, Yeungnam University, 214-1 Dae-dong, Gyeongsan, 712-749, South Korea.
Thiagarajan
T
Madheswaran
Rengarajan
R
Baskaran
Chul Soon
CS
Yong
Bong Kyu
BK
Yoo
D000279:Administration, Cutaneous; D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods; D018120:Finasteride / Q000008:administration & dosage / Q000737:chemistry*; D005989:Glycerides / Q000737:chemistry*; D005990:Glycerol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D050866:Liquid Crystals / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D010539:Permeability; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D013501:Surface-Active Agents / Q000008:administration & dosage / Q000737:chemistry*; D013552:Swine
D005989:Glycerides; D013501:Surface-Active Agents; C022131:cremophor; D011092:Polyethylene Glycols; D018120:Finasteride; C000515:cremophor EL; C005953:monoolein; D005990:Glycerol