Utilizing in vitro drug release assays to predict in vivo drug retention in micelles.

Autor: Varela-Moreira A; CDL Research, University Medical Center Utrecht, Utrecht, the Netherlands; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Utrecht, the Netherlands., van Leur H; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Utrecht, the Netherlands., Krijgsman D; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Utrecht, the Netherlands., Ecker V; Institute for Clinical Chemistry and Pathobiochemistry, School of Medicine, Technical University Munich, Munich, Germany., Braun M; Institute for Clinical Chemistry and Pathobiochemistry, School of Medicine, Technical University Munich, Munich, Germany., Buchner M; Institute for Clinical Chemistry and Pathobiochemistry, School of Medicine, Technical University Munich, Munich, Germany., Fens MHAM; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Utrecht, the Netherlands. Electronic address: m.h.a.m.fens@uu.nl., Hennink WE; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Utrecht, the Netherlands., Schiffelers RM; CDL Research, University Medical Center Utrecht, Utrecht, the Netherlands; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Utrecht, the Netherlands.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2022 Apr 25; Vol. 618, pp. 121638. Date of Electronic Publication: 2022 Mar 05.
DOI: 10.1016/j.ijpharm.2022.121638
Abstrakt: In the present work, we aim at developing an in vitro release assay to predict circulation times of hydrophobic drugs loaded into polymeric micelles (PM), upon intravenous (i.v.) administration. PM based on poly (ethylene glycol)-b-poly (N-2-benzoyloxypropyl methacrylamide) (mPEG-b-p(HPMA-Bz)) block copolymer were loaded with a panel of hydrophobic anti-cancer drugs and characterized for size, loading efficiency and release profile in different release media. Circulation times in mice of two selected drugs loaded in PM were evaluated and compared to the in vitro release profile. Release of drugs from PM was evaluated over 7 days in PBS containing Triton X-100 and in PBS containing albumin at physiological concentration (40 g/L). The results were utilized to identify crucial molecular features of the studied hydrophobic drugs leading to better micellar retention. For the best and the worst retained drugs in the in vitro assays (ABT-737 and BCI, respectively), the circulation of free and entrapped drugs into PM was examined after i.v. administration in mice. We found in vivo drug retention at 24 h post-injection similar to the retention found in the in vitro assays. This demonstrates that in vitro release assay in buffers supplemented with albumin, and to a lesser degree Triton X-100, can be employed to predict the in vivo circulation kinetics of drugs loaded in PM. Utilizing media containing acceptor molecules for hydrophobic compounds, provide a first screen to understand the stability of drug-loaded PM in the circulation and, therefore, can contribute to the reduction of animals used for circulation kinetics studies.
(Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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