Combination of lipid nanoparticles and iontophoresis for enhanced lopinavir skin permeation: Impact of electric current on lipid dynamics

Nanostructured lipid carriers (NLC)-loaded with lopinavir (LPV) were developed for its iontophoretic transdermal delivery. Electronic paramagnetic resonance (EPR) spectroscopy of fatty acid spin labels and differential scanning calorimetry (DSC) were applied to investigate the lipid dynamic behavior of NLC before and after the electrical current. In vitro release and permeation studies, with and without anodic and cathodic iontophoresis were also performed.

NLC-LPV had nanometric size (179.0 ± 2.5 nm), high drug load (∼x223C 4.14%) and entrapment efficiency (EE) (∼x223C 80%). NLC-LPV was chemically and physically stable after applying an electric current. The electrical current reduced EE after 3 h (67.21 ± 2.64%), resulting in faster LPV in vitro release. EPR demonstrated that iontophoresis decreased NLC lipid dynamics, which is a long-lasting effect. DSC studies demonstrated that electrical current could trigger the polymorphic transition of NLC and drug solubilization in the lipid matrix.

NLC-LPV, combined with iontophoresis, allowed drug quantification in the receptor medium, unlike unloaded drugs. Cathodic iontophoresis enabled the quantification of about 7.9 µg/cm² of LPV in the receptor medium. Passive NLC-LPV studies had to be done for an additional 42 h to achieve similar concentrations. Besides, anodic iontophoresis increased by 1.8-fold the amount of LPV in the receptor medium, demonstrating a promising antiviral therapy strategy.

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Materials: LPV (≥ 99%) (MW 628.8 Da) was kindly donated by Cristália Indústria Farmacêutica (Itapira, Brazil) and IQUEGO (Indústria Química do Estado de Goiás, Goiânia, Brazil). HPLC grade acetonitrile was purchased from J. T. Baker (Phillipsburg, NJ, USA). Tween® 80, Span® 80, Span® 85, Pluronic® F-127, Pluronic® F-68, sodium taurodeoxycholate, oleic acid and spin label (5-doxyl stearic acid, 5-DSA) were purchased from Sigma Aldrich (St. Louis, MO, USA). Plurol® Oleic CC, Gelucire® 48/16 and Labrasol® were kindly donated by Gattefossé (France). Stearic acid (mp 58.77 °C) was from Vetec (São Paulo, Brazil). Ultrapurified water was used. All other chemicals were of analytical grade.

Article information: Rayssa Barbary Pedroza Moura, Lígia Marquez Andrade, Lais Alonso, Antonio Alonso, Ricardo Neves Marreto, Stephânia Fleury Taveira, Combination of lipid nanoparticles and iontophoresis for enhanced lopinavir skin permeation: Impact of electric current on lipid dynamics, European Journal of Pharmaceutical Sciences, Volume 168, 2022. https://doi.org/10.1016/j.ejps.2021.106048.