Effect of new Curcumin-containing nanostructured lipid dispersions on human keratinocytes proliferative responses

The present study describes the production and characterization of nanostructured lipid dispersions (NLD) containing curcumin (CUR) as new tools for curcumin topical delivery. Four types of NLD based on monoolein in association with different emulsifiers were produced: Na cholate and poloxamer 407 (NLD1), poloxamer alone (NLD2), the mixture of Na cholate and Na caseinate (NLD3) and Na cholate alone (NLD4). Morphology, dimensional distribution of lipid dispersions were investigated by cryo-TEM and Photon Correlation Spectroscopy (PCS). In vitro studies based on Franz cell, membrane nylon and stratum corneum-epidermis (SCE) were carried out in order to compare the four NLDs in term of cytotoxicity in human keratinocytes and CUR diffusion. Our PCS studies showed differences in particles diameter among the different NLDs. In addition, cytotoxicity results in HaCaT cells evidenced that NLD1 and NLD2 were toxic at doses over 1 μM. Therefore Cryo-TEM was determined only for NLD3 and NLD4 showing that CUR did not affect their structure. Diffusion measurement in SCE and nylon membrane evidenced that CUR had a time delayed release for NLD4. The “wound healing” effect of NLD3 and NLD4 with and without CUR was analysed keratinocytes in vitro and a clear inhibition of cell proliferation/migration by CUR was observed. This effect was mediated by the inhibition of cyclin D1 expression as a consequence of the impaired NFkB activation. This study confirms the antiproliferative properties of CUR and evidenced a new possible model of CUR topical delivery for hyperproliferative cutaneous diseases such as psoriasis.