Optimization of nanostructured lipid carriers for Zidovudine delivery using a microwave-assisted production method

• Published in: European journal of pharmaceutical sciences 2018-09, Vol.122, p.22-30
• Main Authors: Cavalcanti, S.M.T., Nunes, C., Costa Lima, S.A., Soares-Sobrinho, J.L., Reis, S.
• Format: Article
• Language: English
• Subjects: Anti-viral drug; Design of experiments (DOE); In vitro drug release assays; Jurkat cells; Lipid nanoparticles; Microwave; Quality by Design (QbD)
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2018.06.017

An adapted methodology for obtaining lipid nanoparticles that only uses the microwave reactor in the synthesis process was developed. The method has the following features: one-pot, one-step, fast, practical, economical, safe, readiness of scaling-up, lack of organic solvents and production of nanoparticles with low polydispersity index (PDI) (below 0.3). This new method was applied for the development of nanostructured lipid carriers (NLC) loaded with a hydrophilic drug, the antiretroviral agent zidovudine (AZT). The aim of the present work was to develop, evaluate and compare optimized NLC formulations produced by two different methods – hot ultrasonication and microwave-assisted method. The development and optimization of the NLC formulations were supported by a Quality by Design (QbD) approach. All formulations were physicochemically characterized by the same parameters. The optimized formulations presented a suitable profile for oral administration (particle size between 100 and 300 nm, PDI −20 mV). Furthermore, the morphologies assessed by TEM showed spherical shape and confirmed the results obtained by DLS. Both AZT loaded formulations were physically stable for at least 45 days and non-toxic on Jurkat T cells. Drug release studies showed a controlled release of AZT under gastric and plasma-simulated conditions. [Display omitted]