Schlosser, Corinna S;
Rozek, Wojciech;
Mellor, Ryan D;
Manka, Szymon W;
Morris, Christopher J;
Brocchini, Steve;
Williams, Gareth R;
(2024)
A lipid-based delivery platform for thermo-responsive delivery of teriparatide.
International Journal of Pharmaceutics
, Article 124853. 10.1016/j.ijpharm.2024.124853.
(In press).
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Abstract
Teriparatide (and analogue peptides) are the only FDA approved anabolic treatments for osteoporosis. Current therapies are administered as a daily subcutaneous injection, which limits patient adherence and clinical efficacy. To achieve the desired anabolic effect, a controlled delivery system must ensure a pulsatile release profile over a prolonged period. Thermo-responsive formulations (e.g. liposomes) can undergo a temperature-related phase-transition which can allow active control of drug release. Herein, thermo-responsive liposomes were developed to permit precise control over the teriparatide release rate through modulation of temperature. Entrapment of hydrophilic molecules, including peptides within liposomes remains challenging due to the large volume of hydration. In this work, hydrophobic ion pairing was employed for the first time to enhance peptide entrapment within liposomes. The method resulted in a hydrophobic complex that achieved high teriparatide entrapment (>75 %) in sub-200 nm, monodispersed liposomes. Hydrophobic ion pairing outperformed other entrapment approaches. Several liposomal formulations with transition temperatures between 38 – 50 °C were obtained by modulation of the phospholipid composition. In vitro release assays demonstrated temperature-dependent release kinetics with faster rates of release observed at/above the transition temperature. The maintenance of biological activity of released teriparatide was demonstrated in a cell-based assay utilising the PTH1 receptor. Overall, this provides the first proof-of-concept of the suitability of thermo-responsive systems for pulsatile delivery of teriparatide and similar peptides.
| Type: | Article |
|---|---|
| Title: | A lipid-based delivery platform for thermo-responsive delivery of teriparatide |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ijpharm.2024.124853 |
| Publisher version: | http://dx.doi.org/10.1016/j.ijpharm.2024.124853 |
| Language: | English |
| Additional information: | © 2024 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
| Keywords: | Thermo-responsive liposomes, Teriparatide, PTH1R, Controlled release, Pulsatile, Hydrophobic-ion-pairin |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10198826 |
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