Solid lipid nanoparticles self-assembled from spray dried microparticles

Sanchez-Vazquez, Brenda; Lee, Jong Bong; Strimaite, Margarita; Buanz, Asma; Bailey, Russell; Gershkovich, Pavel; Pasparakis, George; Williams, Gareth R.

Abstract

We report the self-assembly of drug-loaded solid lipid nanoparticles (SLNs) from spray dried microparticles comprising poly(vinylpyrrolidone) (PVP) loaded with glyceryl tristearate (GTS) and either indomethacin (IMC) or 5-fluorouracil (5-FU). When the spray dried microparticles are added to water, the PVP matrix dissolves and the GTS and drug self-assemble into SLNs. The SLNs provide a non-toxic delivery platform for both hydrophobic (IMC) and hydrophilic (5-FU) drugs. They show extended release profiles over more than 24 h, and in permeation studies the drug cargo is seen to accumulate inside cancer cells. This overcomes major issues with achieving local intestinal delivery of these active ingredients, in that IMC permeates well and thus will enter the systemic circulation and potentially lead to side effects, while 5-FU remains in the lumen of the small intestine and will be secreted without having any therapeutic benefit. The SLN formulations are as effective as the pure drugs in terms of their ability to induce cell death. Our approach represents a new and simple route to the fabrication of SLNs: by assembling these from spray-dried microparticles on demand, we can circumvent the low storage stability which plagues SLN formulations.

Citation

Sanchez-Vazquez, B., Lee, J. B., Strimaite, M., Buanz, A., Bailey, R., Gershkovich, P., Pasparakis, G., & Williams, G. R. (2019). Solid lipid nanoparticles self-assembled from spray dried microparticles. International Journal of Pharmaceutics, 572, Article 118784. https://doi.org/10.1016/j.ijpharm.2019.118784

• Journal Article Type: Article
• Acceptance Date: Oct 10, 2019
• Online Publication Date: Oct 30, 2019
• Publication Date: Dec 15, 2019
• Deposit Date: Jan 3, 2020
• Publicly Available Date: Oct 31, 2020
• Journal: International Journal of Pharmaceutics
• Print ISSN: 0378-5173
• Electronic ISSN: 1873-3476
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 572
• Article Number: 118784
• DOI: https://doi.org/10.1016/j.ijpharm.2019.118784
• Keywords: Spray-drying; Self-assembly; Solid lipid nanoparticle; Drug delivery system; Stability
• Public URL: https://nottingham-repository.worktribe.com/output/3611542
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0378517319308294