Silicon-Based Linkers for Tunable Acid-Sensitive Drug Release from Polymeric Nanoparticles.

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Tác giả: Wim E Hennink, Marco Kong, Rob M J Liskamp, Tommi Meulemans, Cristianne Rijcken, Peter Schuckman, Matt Timmers, Tina Vermonden

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: Germany : Chemistry (Weinheim an der Bergstrasse, Germany) , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 689090

Active Pharmaceutical Ingredients (APIs) may benefit from a carrier to improve their pharmacokinetic and pharmacodynamic properties. Core-crosslinked polymeric micelles (CCPMs) are carriers for hydrophobic small molecule APIs. In CCPMs, APIs are generally covalently coupled to the core of the micelles by use of a linker, which can be tailored to adjust the release rate of the API. Acid triggered release is promising because of local acidic environment in the tissue of interest, and expected uptake via endocytosis. In the present study, silyl-based linkers were synthesized, and attached to gemcitabine as model API to investigate the tunability of release by introduction of different substituents. Attachment was achieved via an Si ether bond, with the linker coupled to the primary alcohol functionality on gemcitabine. By varying the substituents on the silyl atom, we could vary the release half-life (t
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