Magnetic beads for the evaluation of drug release from biotinylated polymeric micelles in biological media

• Published in: Journal of controlled release 2022-09, Vol.349, p.954-962
• Main Authors: Wang, Yan, Fens, Marcel H., van Kronenburg, Nicky C.H., Shi, Yang, Lammers, Twan, Heger, Michal, van Nostrum, Cornelus F., Hennink, Wim E.
• Format: Article
• Language: English
• Subjects: Biotin; Drug release; Polymeric micelles; Streptavidin-coated magnetic beads
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2022.07.044

To improve the reliability of in vitro release studies of drug delivery systems, we developed a novel in vitro method for the evaluation of drug release from polymeric micelles in complex biological media. Polymeric micelles based on poly(N-2-hydroxypropyl methacrylamide)-block-poly(N-2-benzoyloxypropyl methacrylamide) (p(HPMAm)-b-p(HPMAm-Bz)) of which 10% of the chains was functionalized with biotin at the p(HPMAm) terminus were prepared using a solvent extraction method. The size of the micelles when loaded with a hydrophobic agent, namely paclitaxel (a clinically used cytostatic drug) or curcumin (a compound with multiple pharmacological activities), was around 65 nm. The biotin decoration allowed the binding of the micelles to streptavidin-coated magnetic beads which occurred within 10 min and reached a binding efficiency of 90 ± 6%. Drug release in different media was studied after the magnetic separation of micelles bound to the streptavidin-coated beads, by determination of the released drug in the media as well as the retained drug in the micellar fraction bound to the beads. The in vitro release of paclitaxel and curcumin at 37 °C in PBS, PBS containing 2% v/v Tween 80, PBS containing 4.5% w/v bovine serum albumin, mouse plasma, and whole mouse blood was highly medium-dependent. In all media studied, paclitaxel showed superior micellar retention compared to curcumin. Importantly, the presence of serum proteins accelerated the release of both paclitaxel and curcumin. The results presented in this study show great potential for predicting drug release from nanomedicines in biological media which in turn is crucial for their further pharmaceutical development. [Display omitted] •A ‘fishing’ approach is proposed to study drug release from biotinylated polymeric micelles using streptavidin-coated magnetic beads.•The novel release method allows the simultaneous determination of the released drug in various media as well as the retained drug in the micellar fraction bound to the beads.•The in vitro release of paclitaxel and curcumin is highly medium-dependent, pointing out the importance of the appropriate selection of release medium in the evaluation of drug release from nanomedicines•The proposed ‘fishing’ approach shows great potential for predicting drug release from nanomedicines in a broad range of biological media.