Development and in vivo validation of phospholipid-based depots for the sustained release of bupivacaine.

Aleandri, Simone; Rahnfeld, Lisa; Chatzikleanthous, Despo; Bergadano, Alessandra; Bühr, Claudia; Detotto, Carlotta; Fuochi, Sara; Weber-Wilk, Kevin; Schürch, Stefan; van Hoogevest, Peter; Luciani, Paola (2022). Development and in vivo validation of phospholipid-based depots for the sustained release of bupivacaine. European journal of pharmaceutics and biopharmaceutics, 181, pp. 300-309. Elsevier 10.1016/j.ejpb.2022.11.019

Preview

Text 1-s2.0-S0939641122002776-main.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (9MB) | Preview

By direct deposition of the drug at the local site of action, injectable depot formulations - intended for treatment of a local disease or for local intervention - are designed to limit the immediate exposure of the active principle at a systemic level and to reduce the frequency of administration. To overcome known drawbacks in the production of some marketed phospholipid-based depots, here we propose to manufacture drug-loaded negatively charged liposomes through conventional technologies and to control their aggregation mixing a solution of divalent cations prior to administration. We identified phosphatidylglycerol (PG) as the most suitable phospholipid for controlled aggregation of the liposomes and to modulate the release of the anesthetic bupivacaine (BUP) from liposomal depots. In vivo imaging of the fluorescently-labelled liposomes showed a significantly higher retention of the PG liposomes at the injection site with respect to neutral ones. In situ mixing of PG liposomes with calcium salts significantly extended the area under the curve of BUP in plasma compared to the non-depot system. Overall, controlling the aggregation of negatively charged liposomes with divalent cations not only modulated the particle clearance from the injection site but also the release in vivo of a small amphipathic drug such as BUP.

Interest & Impact

Downloads

19 since deposited on 28 Nov 2022
19 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item