Characterization of Nanoparticles Made of Ethyl Cellulose and Stabilizing Lipids: Mode of Manufacturing, Size Modulation, and Study of Their Effect on Keratinocytes.

We have developed an ethyl cellulose-based nanoparticulate system for encapsulation of sparingly soluble active pharmaceutical ingredients. Cannabidiol (CBD) and curcumin (CUR) were selected as model active ingredients. Using the nanoprecipitation method, nanoparticles ranged between 150 nm and 250 nm were obtained with an entrapment efficiency of >80%. It has been shown that incorporation of stabilizing lipids significantly reduced aggregation, increased the yield and the active ingredient-to-polymer ratio. In this study, we have explored the influence of process parameters on the extent of new particle core formation: chemical properties of the active ingredients, polymer concentrations, non-solvent addition rate, and the volume of the organic solvent for nanoparticle size control. The relationship between the particle radius [R] and the polymer concentration [Pol] was defined by R ∝ [Pol]n when n < ⅓. The extent of polymer supersaturation was related to the value of n, when the high polymer supersaturation increased the formation rate of new particle cores while decreasing polymer layering on the existing cores and the nanoparticles size. The obtained nanoparticles have shown low toxicity in keratinocytes, however, higher loadings of CUR or CBD resulted in increased toxicity. The nanoparticles effectively internalized into keratinocytes, implying their applicability for dermal delivery.