Lipid nanovectors for oral delivery of curcumin and evaluation of their performance through PAMPA systems

Abstract

Therapeutic use of curcumin is strongly limited by low oral bioavailability [1]. Our work was focused on the development and characterization of different lipid nanovectors, namely solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and microemulsions containing curcumin. A comparison of their in vitro performance was carried out by Parallel Artificial Membrane Permeability Assay (PAMPA), a validated artificial method easy to use for predicting in vivo gastro-enteric permeability. The vectors were fully characterized, and stability and in vitro drug release were also investigated. The optimized Compritol® 888 ATO SLN formulation showed a mean particle size lower than 300nm, a zeta potential of -33 mV and 80% drug entrapment efficiency. It was stable over one month. The presence of round shape SLN with homogeneous size distribution was confirmed by TEM analysis. NLCs formulations contain 80% Compritol, 20% vitamin E or 95% glyceryl monostearate, 5% vitamin E. Both contain Poloxamer 188 and 20 mg of curcumin. Sizes were below 300nm and drug entrapment efficiency was about 60%. In both NLCs and SLNs, an immediate release of the curcumin within 30 minutes was evidenced, followed by a plateau phase for ca. 5 – 6 hours. PAMPA systems showed a considerable increasing of the amount of curcumin permeated in both SLNs and NLCs compared to curcumin suspension. Three microemulsions were developed using Cremophor EL, Tween 20, Tween 80 or Lecitin, olive oil, wheat germ oil, vitamin E. The optimized microemulsion contains vitamin E (3.3%), Tween® 20 (53.8%), ethanol (6.6%) and water (36.3%). It resulted the best in terms of size, polidispersity, encapsulation efficiency and positive influence on the solubility of curcumin (14.57 mg/ml). The microemulsion is stable for two months and showed a permeation % through the artificial membrane of about 70%. SLNs, NLCs and microemulsions offer a promising delivery systems for improving oral bioavailability of curcumin.