Enhancement of topical delivery from biodegradable nanoparticles

• Published in: Pharmaceutical research 2004-10, Vol.21 (10), p.1818-1825
• Main Authors: Alvarez-Román, Rocío, Naik, Aarti, Kalia, Yogeshvar N, Guy, Richard H, Fessi, Hatem
• Format: Article
• Language: English
• Subjects: Administration, Topical; Animals; Chromatography, High Pressure Liquid; Drug Carriers; Drug Compounding; Drug Delivery Systems; Fluorescent Dyes; In Vitro Techniques; Microscopy, Confocal; Microspheres; Nanoparticles; Permeability; Polyesters; Skin Absorption; Solubility; Swine
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1023/B:PHAM.0000045235.86197.ef

To determine whether and how encapsulation of lipophilic compounds in polymeric nanoparticles is able to improve topical delivery to the skin. The penetration of octyl methoxycinnamate (OMC; Parsol MCX), a highly lipophilic sunscreen, into and across porcine ear skin in vitro was investigated, subsequent to encapsulation in poly(epsilon-caprolactone) nanoparticles, using tape-stripping. Confocal laser scanning microscopy (CLSM) was used to visualize the distribution of nanoparticles, charged with Nile red (NR), a lipophilic and fluorescent dye. Quantification of OMC in the skin using tape-stripping demonstrated that nanoparticulate encapsulation produced a 3.4-fold increase in the level of OMC within the stratum corneum (SC), although the use of nanoparticles did not appear to increase skin permeation (it was not possible to detect OMC in the receiver compartment after 6 h). The confocal images showed that the fluorescence profile observed in the skin after application of NR-containing nanoparticles was clearly different from that seen following application of NR dissolved in propylene glycol. Two hours postapplication of NR-containing nanoparticles, fluorescence was perceptible at greater depths (up to 60 microm) within the skin. i) Nanoparticulate encapsulation of OMC increased its "availability" with the SC. ii) The altered distribution of NR when delivered via nanoparticles was due, at least in part, to its altered thermodynamic activity (relative to that in propylene glycol) and, as a result, an increase in its partition coefficient into the SC.