Evaluation of lipid-stabilised tripropionin nanodroplets as a delivery route for combretastatin A4

• Published in: International journal of pharmaceutics Vol. 526; no. 1-2; pp. 547 - 555
• Main Authors: Mico, Victoria, Charalambous, Antonia, Peyman, Sally A., Abou-Saleh, Radwa H., Markham, Alexander F., Coletta, P. Louise, Evans, Stephen D.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.06.2017
• Subjects: Animals; Cells, Cultured; Combretastatin; Drug delivery; Endothelial Cells - drug effects; Mice; Nanoemulsion; Nanoparticles - chemistry; Oils - chemistry; Stilbenes - administration & dosage; Triglycerides - chemistry; Combretastatin; Drug delivery; Nanoemulsion
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2017.05.009

[Display omitted] Lipid-based nanoemulsions are a cheap and elegant route for improving the delivery of hydrophobic drugs. Easy and quick to prepare, nanoemulsions have promise for the delivery of different therapeutic agents. Although multiple studies have investigated the effects of the oil and preparation conditions on the size of the nanoemulsion nanodroplets for food applications, analogous studies for nanoemulsions for therapeutic applications are limited. Here we present a study on the production of lipid-stabilised oil nanodroplets (LONDs) towards medical applications. A number of biocompatible oils were used to form LONDs with phospholipid coatings, and among these, squalane and tripropionin were chosen as model oils for subsequent studies. LONDs were formed by high pressure homogenisation, and their size was found to decrease with increasing production pressure. When produced at 175MPa, all LONDs samples exhibited sizes between 100 and 300nm, with polydispersity index PI between 0.1 and 0.3. The LONDs were stable for over six weeks, at 4°C, and also under physiological conditions, showing modest changes in size (<10%). The hydrophobic drug combretastatin A4 (CA4) was encapsulated in tripropionin LONDs with an efficiency of approximately 76%, achieving drug concentration of approximately 1.3mg/ml. SVR mouse endothelial cells treated with CA4 tripropionin LONDs showed the microtubule disruption, characteristic of drug uptake for all tested doses, which suggests successful release of the CA4 from the LONDs.