Sustained in-vivo release of triptorelin acetate from a biodegradable silica depot: Comparison to Pamorelin® LA

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openAccess

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Volume Title

A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Date

2021-06-16

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Mcode

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Language

en

Pages

14

Series

Nanomaterials, Volume 11, issue 6

Abstract

Triptorelin acetate was encapsulated into silica microparticles by spray-drying a mixture of colloidal silica sol and triptorelin acetate solution. The resulting microparticles were then combined with another silica sol containing silica nanoparticles, which together formed an injectable silica-triptorelin acetate depot. The particle size and surface morphology of the silica-triptorelin acetate microparticles were characterized together with the in vitro release of triptorelin, injectability and rheology of the final injectable silica-triptorelin acetate depot. In vivo pharmacokinetics and pharmacodynamics of the silica-triptorelin acetate depot and Pamorelin® were evaluated and compared in Sprague-Dawley male rats after subcutaneous administration. Serum samples up to 91 days were collected and the plasma concentrations of triptorelin and testosterone were analyzed with ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). In vivo pharmacokinetics showed that injections of the silica-triptorelin acetate depot gave 5-fold lower Cmax values than the corresponding Pamorelin® injections. The depot also showed a comparable sustained triptorelin release and equivalent pharmacodynamic effect as the Pamorelin® injections. Detectable triptorelin plasma concentrations were seen with the depot after the 91-day study period and testosterone plasma concentrations remained below the human castration limit for the same period.

Description

Funding Information: Funding: Funding support from Ferring Pharmaceutical A/S is acknowledged. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

Controlled release, Silica hydrogel, Silica microparticles, Silica nanoparticles, Triptorelin

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Citation

Forsback , A-P , Noppari , P , Viljanen , J , Mikkola , J , Jokinen , M , Leino , L , Bjerregaard , S , Borglin , C & Halliday , J 2021 , ' Sustained in-vivo release of triptorelin acetate from a biodegradable silica depot: Comparison to Pamorelin® LA ' , Nanomaterials , vol. 11 , no. 6 , 1578 . https://doi.org/10.3390/nano11061578