RESUMO
Lipid nanoparticles have proved an attractive approach for drug delivery; however, the challenges of optimising formulation stability and increasing drug loading have limited progression. In this work, we investigate the role of unpegylated lipid surfactants (helper lipids) in nanoparticle formation and the effect of blending helper lipids with pegylated lipid surfactants on the formation and stability of lipid-based nanoparticles by nanoprecipitation. Furthermore, blends of unpegylated/pegylated lipid surfactants were examined for ability to accommodate higher drug loading formulations by means of a higher weight percentage (wt%) of drug relative to total mass of formulation components (i.e. drug, surfactants and lipids). Characterisation included evaluation of particle diameter, size distribution, drug loading and nanoformulation stability. Our findings demonstrate that the addition of unpegylated lipid surfactant (Lipoid S100) to pegylated lipid surfactant (Brij S20) enhances stability, particularly at higher weight percentages of the core material. This blending approach enables drug loading capacities exceeding 10% in the lipid nanoparticles. Notably, Lipoid S100 exhibited nucleating properties that aided in the formation and stabilisation of the nanoparticles. Furthermore, we examined the incorporation of a model drug into the lipid nanoparticle formulations. Blending the model drug with the core material disrupted the crystallinity of the core, offering additional potential benefits in terms of drug release and stability. This comprehensive investigation provides valuable insights into the interplay between surfactant properties, core material composition, and nanoparticle behaviour. The study enhances our understanding of lipid materials and offers guidance for the design and optimisation of lipid nanoparticle formulations.
RESUMO
Human Immunodeficiency Virus (HIV) is a global health concern to which nanomedicine approaches provide opportunities to improve the bioavailability of existing drugs used to treat HIV.In this article, lipid polymer hybrid nanoparticles (LPHNs) were developed as a system to provide a combination drug delivery of two leading antiretroviral drugs; darunavir (DRV) and its pharmacokinetic enhancer ritonavir (RTV).The LPHNs were designed with a poly(D, l-lactide-co-glycolide) (PLGA) core, and soybean lecithin (SBL) and Brij 78 as the stabilizers. The LPHNs were prepared by modified nanoprecipitation and the effect of synthetic conditions on the particle properties was studied, which included the Z-average diameter and polydispersity index of LPHNs in water and phosphate buffered saline, and the morphology of the particles. This investigation aimed to prepare a formulation that could be stored in its dry and redispersible form, therefore avoiding the challenges associated with storage of dispersions. The optimum ratio of stabilizer to polymer core was established at 20% w/w, and Brij 78 was found to be crucial in providing colloidal stability in physiological solutions; the minimum amount of Brij 78 required to provide stability in phosphate buffered saline was 70% w/w of the total stabilizer mass. Viable formulations of LPHNs containing DRV and RTV in the clinically used 8:1 ratio were prepared containing 20% w/w DRV with respect to the PLGA mass. The use of cryoprotectant, polyethylene glycol, combined with freeze-drying yielded LPHNs with a Z-average diameter of 150 nm when the particles were re-dispersed in water. The oral absorption behavior was assessed using an in vitro triple culture model. Whilst the use of cryoprotectant and freeze-drying led to no improvement of the transcellular permeability compared to the unformulated drugs, the non-freeze-dried samples with the highest soybean lecithin led to increased transcellular permeability, revealing the potential of LPHNs for enhancing HIV treatment.
