Polymer Nanoparticles with Silicon-Based Linkers for Drug Release

Author: Catharina Goedecke
Published On: December 17, 2024
Copyright: Wiley-VCH GmbH

Releasing the active ingredients of pharmaceuticals in a targeted manner can be useful to improve their intended effects and reduce side effects. For this they can be, e.g., encapsulated in nanoparticles or covalently connected to a carrier molecule. Certain triggers can be used for their targeted release. For example, tumor tissues can create an acidic environment. Existing linkers that covalently connect drug molecules to carriers and break apart under acidic conditions can suffer from a lack of tunability, i.e., altering the release characteristics can be challenging.

Matt Timmers, Utrecht University, The Netherlands, and Cristal Therapeutics, Maastricht, The Netherlands, Rob M.J. Liskamp, Cristal Therapeutics, University of Glasgow, UK, and Maastricht University, The Netherlands, and colleagues have used silyl-based linkers together with nanosized polymeric micelles for the tunable, acid-sensitive release of the anticancer drug gemcitabine (simplified process pictured). The team used core-crosslinked polymeric micelles (CCPMs) made from a block copolymer consisting of polyethylene glycol (PEG) and a lactate-modified N-(2-hydroxypropyl) methacryl amide (HPMA).

The drug was coupled to the silicon-based linker via an ether bond to the primary alcohol functionality on gemcitabine. The linkers also contain a methacrylate unit that allows them to be integrated into the polymer, as well as two substituents (pictured in pink) that can be varied to tune the release properties. By varying the substituents on the silyl unit, the researchers were able to vary the release half-life of the drug between < 1 h and > 96 h at pH 5.0. The team’s new class of silicon-based linkers is easy to prepare and modify and can be linked to different OH-functionalized active pharmaceutical ingredients.