Solid and liquid lipid-based binary solid lipid nanoparticles of diacerein: in vitro evaluation of sustained release, simultaneous loading of gold nanoparticles, and potential thermoresponsive behavior

Abstract

Mubashar Rehman,1 Asadullah Madni,1 Ayesha Ihsan,2 Waheed Samraiz Khan,2 Muhammad Imran Khan,1 Muhammad Ahmad Mahmood,1 Muhammad Ashfaq,1 Sadia Zafar Bajwa,2 Imran Shakir31Department of Pharmacy, Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, Pakistan; 2Nanobiotechnology Group, Industrial Biotechnology Division, National Institute of Biotechnology and Genetic Engineering, Faisalabad, Pakistan; 3Sustainable Energy Technologies (SET) centre, College of Engineering, King Saud University, Riyadh, Saudi ArabiaAbstract: Binary fatty acid mixture-based solid lipid nanoparticles (SLNs) were prepared for delivery of diacerein, a novel disease-modifying osteoarthritis drug, with and without simultaneously loaded gold nanoparticles (GNPs). In order to optimize SLNs for temperature-responsive release, lipid mixtures were prepared using different ratios of solid (stearic acid or lauric acid) and liquid (oleic acid) fatty acids. SLNs were prepared by microemulsification (53 nm), hot melt encapsulation (10.4 nm), and a solvent emulsification-evaporation technique (7.8 nm). The physicochemical characteristics of SLNs were studied by Zetasizer, Fourier transform infrared, and X-ray diffraction analysis. High encapsulation of diacerein was achieved with diacerein-loaded and simultaneously GNP-diacerein-loaded SLNs. In vitro dissolution studies revealed a sustained release pattern for diacerein over 72 hours for diacerein-loaded SLNs and 12 hours for GNP-diacerein-loaded SLNs. An increase in diacerein payload increased the release time of diacerein while GNPs decreased it. In addition, rapid release of diacerein over 4 hours was observed at 40°C (melting point of optimized fatty acid mixture), demonstrating that these binary SLNs could be used for thermoresponsive drug delivery. Kinetic modeling indicated that drug release followed zero order and Higuchi diffusion models (R2>0.9), while the Korsmeyer-Peppas model predicted a diffusion release mechanism (n<0.5).Keywords: diacerein, thermoresponsive, binary, gold nanoparticles, lipids, nanoparticles