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

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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.

Item Type:

Journal Article (Original Article)


08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP)
04 Faculty of Medicine > Faculty Institutions > Experimental Animal Center (EAC)

UniBE Contributor:

Aleandri, Simone, Rahnfeld, Lisa, Chatzikleanthous, Despo, Bergadano, Alessandra, Bühr, Claudia, Detotto, Carlotta, Fuochi, Sara, Schürch, Stefan, Luciani, Paola


500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry
600 Technology > 610 Medicine & health








Pubmed Import

Date Deposited:

28 Nov 2022 11:22

Last Modified:

10 Dec 2022 00:16

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

bupivacaine depot formulation liposomal aggregates long-acting injectables negatively charged phospholipids sustained release




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