Explosomes: A new modality for DEB-TACE local delivery of sorafenib: In vivo proof of sustained release

Abstract

The current medical practice in treating Hepatocellular carcinoma (HCC) using Drug Eluting Transarterial chemoembolization (DEB-TACE) technique is limited only to hydrophilic ionizable drugs, that can be attached ionically to the oppositely charged beads. This limitation has forced physicians to subscribe the more hydrophobic, first treatment option drugs, like sorafenib systemically via the oral route, thus flooding the patient system with a very powerful, non-specific, multiple-receptor tyrosine kinase inhibitor that is associated with notorious side effects. In this paper, a new modality is introduced, where highly charged, drug loaded liposomes are added to oppositely charged DEBs in a manner causing them to “explode” and the drug is eventually attached to the beads in the lipid patches covering their surfaces; therefore we call them “Explosomes”. After fully describing the preparation process and in vitro characterization, this manuscript delves into an in vivo pharmacokinetic study over 50 New Zealand rabbits, where explosomal loading is challenged vs oral as well as current practice of emulsifying sorafenib in lipiodol. Over 14 days of follow up, and compared to other groups, explosomal loading of SRF on embolic beads proved to cause a slower release pattern with longer Tmax, lower Cmax and less washout to general circulation in healthy animals. This treatment modality opens a new untapped door for local sustained delivery of hydrophobic drugs in catheterized organs.