Development of a phospholipid-based depot technology for sustained drug release

Prof. Dr. P. Luciani1), University Bern/Switzerland

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Prof. Dr. Paola LucianiDepartment for Chemistry and Biochemistry, University Bern, Freiestr. 3, CH-3012 Bern, Switzerland

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By direct deposition of the drug at the site of action, injectable depot formulations enable to limit the immediate exposure of the active principle at a systemic level and to reduce the frequency of administration.1)2)3) A reliable, steady, and prolonged drug release achieved with a biocompatible system that can be conveniently produced and administered is an appealing solution to address various unmet clinical needs. Aim of the present research proposal is to develop a novel manufacturing process for lipid-based depots as an alternative to current technologies, such as the multivesicular liposomal platform DepoFoam®. We propose to prepare sterile drug-loaded liposomes through conventional technologies and to induce their depot aggregation by mixing the negatively charged vesicles with a solution of divalent cations immediately prior to administration. With the aid of a dual-chamber syringe, the two independent sterile isotonic solutions can be handily mixed and directly injected. Such an easy manufacturing process can boost the interest of companies and academia towards novel phospholipid-based injectables intended for pain management and towards novel lipid-based products, with a focus on hydrophilic drugs, addressing specific clinical demands.

Benefit for the community

The new methodology proposed in this research proposal could boost the interest towards this dosage form. A depot injectable production process characterized by manufacturing requirements less cumbersome than the one of the DepoFoam® technology could attract the interest of several companies and research groups, then willing to consider phospholipids for the development of new drug products.

Besides proposing new alternatives for delivery of drugs prescribed for the management of postsurgical pain, several other active principles, even the ones not available for local release at the moment, could benefit from this technology. Avoiding systemic exposure to drugs with their long-term adverse effects and reducing compliance-related problems using sustained release systems could be a tremendous step forward in the field vascularized allo-transplantation, solid organ transplantation or in the treatment of inflammatory skin disease.

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Katre NJ, 2004
Liposome-based depot injection technologies: How versatile are they?
Am. J. Drug Deliv. 2, 213–227
Van Hoogevest P, Luciani P, 2018
Recent advances in the use of phospholipid excipients in local or injectable depot formulations
Pharmind 8, 1104–1109
Wright JC, Burgess DJ, 2012
Long acting injections and implants
New York: Springer
Publications derived from the project:
Rahnfeld L, Thamm J, Steiniger F, van Hoogevest P, Luciani P, 2018
Study on the in situ aggregation of liposomes with negatively charged phospholipids for use as injectable depot formulation
Colloids Surf. B Biointerfaces 168, 10–17
Weber F, Rahnfeld L, Luciani P, 2020
Analytical profiling and stability evaluation of liposomal drug elivery systems: a rapid UHPLC-CAD-based approach for phospholipids in research and quality control
Talanta 220, 121320
Rahnfeld L, Luciani P, 2020
Injectable lipid depot formulations: where do we stand?
Pharmaceutics 12, 567
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