Isely Christopher, Atube Kidochukwu J, Cheung Candice V, Steege Christine F, Pellechia Perry J, Gower R Michael
Department of Chemical Engineering, University of South Carolina, Columbia, SC 29208, USA.
Biomedical Engineering Program, University of South Carolina, Columbia, SC 29208, USA.
ACS Appl Polym Mater. 2022 Apr 8;4(4):2269-2282. doi: 10.1021/acsapm.1c01066. Epub 2022 Mar 16.
The oil in water emulsion/solvent extraction method is used to fabricate many FDA approved, polymer particle formulations for drug delivery. However, these formulations do not benefit from surface functionalization that can be achieved through tuning particle surface chemistry. Poly(vinyl alcohol) (PVA) is the emulsifier used for many FDA approved formulations and remains associated with the particle surface after fabrication. We hypothesized that the hydroxyl groups in PVA could be conjugated with biomolecules using isothiocyanate chemistry and that these modifications would endow the particle surface with additional functionality. We demonstrate that fluorescein isothiocyanate and an isothiocyanate derivatized mannose molecule can be covalently attached to PVA in a one-step reaction. The modified PVA polymers perform as well as unmodified PVA in acting as an emulsifier for fabrication of poly(lactide-co-glycolide) particles. Particles made with the fluorescein modified PVA exhibit fluorescence confined to the particle surface, while particles made with mannose modified PVA bind concanavalin A. In addition, mannose modified PVA increases particle association with primary macrophages by three-fold. Taken together, we present a facile method for modifying the surface reactivity of polymer particles widely used for drug delivery in basic research and clinical practice. Given that methods are established for conjugating the isothiocyanate functional group to a wide range of biomolecules, our approach may enable PVA based biomaterials to engage a multitude of biological systems.
水包油乳液/溶剂萃取法被用于制备许多经美国食品药品监督管理局（FDA）批准的用于药物递送的聚合物颗粒制剂。然而，这些制剂无法从通过调节颗粒表面化学实现的表面功能化中受益。聚（乙烯醇）（PVA）是许多FDA批准制剂中使用的乳化剂，在制备后仍与颗粒表面相关联。我们假设PVA中的羟基可以使用异硫氰酸酯化学与生物分子共轭，并且这些修饰将赋予颗粒表面额外的功能。我们证明异硫氰酸荧光素和异硫氰酸酯衍生的甘露糖分子可以通过一步反应共价连接到PVA上。改性后的PVA聚合物在作为制备聚（丙交酯-共-乙交酯）颗粒的乳化剂方面表现与未改性的PVA一样好。用异硫氰酸荧光素改性的PVA制成的颗粒在颗粒表面呈现荧光，而用甘露糖改性的PVA制成的颗粒则结合伴刀豆球蛋白A。此外，甘露糖改性的PVA使颗粒与原代巨噬细胞的结合增加了三倍。综上所述，我们提出了一种简便的方法来修饰在基础研究和临床实践中广泛用于药物递送的聚合物颗粒的表面反应性。鉴于已建立将异硫氰酸酯官能团与多种生物分子共轭的方法，我们的方法可能使基于PVA的生物材料能够与多种生物系统相互作用。
