Therapeutic Drug Delivery: Modification and Improvement of Vesosome Preparation

Controlled-release therapeutic delivery in the oncology setting uses drug loaded lipid vesicles as a pay-load carrier to deliver cytotoxic drugs to diseased sites like tumor tissues. When injected in vivo the drug diffuses through the vesicle bilayer continuously. Thus, complete release-control has been elusive as only a few percent of the dose actually reaches the targeted tissue. One route to achieve the desired end delivery dosage is to increase the total amount of vesicles injected into the body. Recently, a second route has been developed, vesosomes, which consist of smaller vesicles encapsulated within a main larger vesicle, are used instead of vesicles to slow the rate of initial leakage. Vesosomes are fabricated in a two step process. The drug solutions are first encapsulated into smaller vesicles, which are in turn encapsulated into a larger vesicle. Currently, the polydispersity and average size of the vesosomes are too large (0.4~5 m m, average 1.3 m m), which causes a lack of control in predicting pharmacokinetic properties and induces premature recognition by the immune system. To reduce the vesosome size and polydispersity, we studied the effects of co-polymer surfactants, which are known to insert into the bilayer and change curvature. We found that polaxamer 188 (P188) was the most effective at reducing the size of the vesicles. P188 concentrations in the range of 1-4 mg/mL could reproducibly yield vesosomes with diameters of 0.3~1 m m (average 0.6 m m ). Thus, the presence of P188 in the vesosome structure provided a narrower distribution and a decrease in the average vesosome diameter.