دانلود رایگان مقاله میسل های پلیمری هیالورونان برای دارورسانی موضعی

ABSTRACT

Nanosized materials offer promising strategy for topical drug delivery due to their enhancing effect on drug percutaneous transport across the stratum corneum barrier. In this work, polymeric micelles made from hydrophobized hyaluronic acid (HA) were probed for skin delivery. Compared to non-polymeric micelle solutions containing similar drug amount, in vitro skin penetration analysis indicated 3 times larger deposition of drug in the epidermis and 6 times larger drug deposition in the dermis after 5 h of topical treatment in Franz diffusion cells. The drug deposition was further increased with prolonged time of topical treatment. Laser confocal microscopy revealed the accumulation of both, the HA forming the vehicle and the payload, in the epidermis and dermis. Although fluorescent labeling of the HA would suggest co-transport of the HA and the drug, loading FRET pair dyes in the micellar core clearly demonstrated gradual micelle disruption with increasing skin depth. Transcellular penetration was the predominant pathway for the loaded drug. The HA polymeric micelles also demonstrated increased bioactivity of loaded compound in vitro and in vivo. In addition, the loaded micelles were found to be stable in cream formulations and thus they have great potential for topical applications for cosmetic and pharmaceutical purposes.

5. Conclusion

HA polymeric micelles enhance skin permeation of loaded compounds. Although the mechanism by which these micelles induce such an effect is not known, the observed data suggest micellar disruption in the topmost skin layers, accompanied by drug release and drug and vehicle penetration into deeper epidermal and dermal layers. The predominant penetration pathway, for both, the HA vehicle and the payload, is transcellular. The HAC18:1 polymeric micelles were also found to improve in vitro and in vivo bioactivity ofthe payload. These micelles are stable after incorporation in o/w cream formulations, and thus represent great potential for topical delivery systems of apolar cosmetic and pharmaceutical compounds.