High drug loading solid lipid nanoparticles, nanostructured lipid carriers and nanoemulsions for the dual drug delivery of the HIV drugs darunavir and ritonavir

Abstract

Drug delivery approaches can be used to enhance the bioavailability of current antiretroviral drugs used to treat HIV. Lipid nanocarriers are attractive drug delivery vehicles and these systems can be classified based on their lipid composition into solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs) and nanoemulsions (NEs). In order to develop high drug loading nanoformulations for the treatment of HIV, we investigate the factors that influence the comparative production of SLNs, NLCs and NEs with Imwitor 900k and soybean oil as the solid and liquid lipids respectively. These nanoformulations contained a therapeutically relevant drug mixture of darunavir (DRV) and ritonavir (RTV). We used a simple nanoprecipitation method that does not require any heating of the lipid phase and screened three key formulation factors (lipid concentration, surfactant selection and drug loading) in order to determine their effect on the particle properties and stability of the formulations. Two different surfactants were used, (Brij 78 and Tween 80) which had a significant effect on the ability to form a viable nanodispersion; using Brij 78 as the surfactant resulted in more viable formulations for our lipids. A concentration of the lipid in the organic phase of 4 mg/mL was determined to achieve a good balance between viable formulations and lipid loading resulting in nanoparticles with mean diameters ∼200–300 ​nm. Drug loadings of 10% w/w DRV/total lipid was achieved for SLNs, with loadings of 20% w/w was possible for NLCs and NEs, these values are amongst the highest reported for lipid nanoformulations. All formulations had encapsulation efficiencies of ≥92.5%. Overall, this study shows the versatility of the nanoprecipitation method for producing SLNs, NLCs and NEs. The ability to produce all three formulations with identical compositions (other than the lipids) may allow direct comparison of the biological properties in the future.