Topical Proretinal Nanoparticles: Biological Activities, Epidermal Proliferation and Differentiation, Follicular Penetration, and Skin Tolerability.

Proretinal nanoparticles, the retinilidene-chitosan nanoparticles, have been developed to overcome the physicochemical instability of retinal and to lessen the dose-dependent cutaneous irritation, through sustaining the release of retinoid. Compared to conventional retinal at the same concentration, proretinal nanoparticles had no cytotoxicity and could induce a spontaneously immortalized human keratinocyte line to express more cellular retinoic acid binding protein-2. Compared to rats topically applied with conventional retinal which showed clear skin irritation and inflammation, daily topical application of proretinal nanoparticles to rats for 28 consecutive days produced neither irritation nor inflammation but significantly increased epidermal proliferation, epidermal thickness, cellular retinoic acid binding protein- 2 expression, and up-regulation of various differentiation markers including keratin 5, keratin 10, keratin 14, cellular retinoic acid binding protein-2, and proliferating cell nuclear antigen. Through the use of confocal laser scanning microscopy, we observed the in vivo follicular penetration of proretinal nanoparticles with the depth of penetration independent of postapplication time. Proretinal nanoparticles provide better biological activities of retinoids on epidermis and could eliminate the side effect of retinoid dermatitis.