Paclitaxel-loaded lipid nanoparticles for topical application: the influence of oil content on lipid dynamic behavior, stability, and drug skin penetration

摘要

Paclitaxel (PAC) has shown potential for regulating hyperkeratosis in skin diseases and its encapsulation in lipid nanoparticles could improve topical treatments. So, solid lipid nanoparticles (SLN) and nanostructured lipid carriers with 12.5 % (NLC1) and 25 % (NLC2) oil content were obtained and characterized. Lipid dynamic behavior was investigated through electron paramagnetic resonance spectroscopy (EPR) and comparative evaluations of EPR, and stability and skin permeation studies were performed. High entrapment efficiency was obtained for all formulations (over 90 %). The absence (SLN) or addition of 12.5 % oil (NLC1) did not significantly alter nanoparticle mean diameter, but 25 % oil (NLC2) produced smaller particles (270.6 +/- 13.5 nm). EPR studies showed that 12.5 % oil increased NLC1 fluidity at the surface. Surprisingly, more oil increased NLC2 superficial rigidity, due to the decrease in nanoparticle mean diameter and additional PAC accumulation in the superficial environment. The oil in lipid matrices improved the physicochemical stability of NLC formulations, and drug-oil chemical affinity prevented PAC expulsion during storage time. NLC2 improved PAC skin penetration and was the only formulation capable of enhancing PAC penetration to deeper skin layers (about 6.48 +/- 1.39 mu g/cm(2)). PAC-NLC2 seemed to be very promising nanocarriers for the topical delivery of PAC.