UMR CNRS 8612, Physico-Chimie-Pharmacotechnie-Biopharmacie, Faculté de Pharmacie, Université Paris-Sud 11, 5 rue J.B. Clément, 92290 Châtenay-Malabry, France.
Int J Pharm. 2010 Mar 15;387(1-2):244-52. doi: 10.1016/j.ijpharm.2009.12.016. Epub 2009 Dec 18.
For being fully efficient a targeted delivery system should associate simultaneously multiple functionalities. In this context, the association of several polymeric materials to form composite multifunctional particles can be foreseen. The present work describes the synthesis of different derivates of poly(gamma-benzyl-L-glutamate) and their use for the preparation of nanoparticles exhibiting different properties, including surface hydrophilization by PEG, fluorescence imaging by FITC and target recognition through easy attachment of desired ligands by using the avidin-biotin interaction, after the nanoparticles preparation. Four PBLG derivates were successfully obtained by ring-opening polymerization (ROP) of NCA, using various initiators corresponding to the molecules to be introduced into the copolymers. Further, nanoparticles smaller than 100 nm could be prepared using a nanoprecipitation technique and the presence of the active moieties introduced within the particles as well as their functionality has been checked. Very interestingly, it has been shown that biotin molecules could be efficiently introduced at the surface of the nanoparticles, which (for 75% of the theoretical amount) could be engaged in a complexation with avidin. It is suggested that this strategy offers the possibility to easily decorate these nanoparticles with various recognition ligands for specific targeting applications by using the well known biotin-avidin sandwich technique.
为了实现高效靶向输送系统,应该同时结合多种功能。在这种情况下,可以预见将几种聚合物材料结合起来形成复合多功能颗粒。本工作描述了聚(γ-苄基-L-谷氨酸)的不同衍生物的合成及其在制备具有不同性质的纳米粒子中的应用,包括通过 PEG 进行表面亲水化、通过 FITC 进行荧光成像以及通过使用生物素-亲和素相互作用容易地将所需配体附着到纳米粒子上,从而实现靶向识别,在纳米粒子制备之后。通过使用与要引入共聚物中的分子相对应的各种引发剂,通过开环聚合(ROP)成功获得了四种 PBLG 衍生物。此外,使用纳米沉淀技术可以制备小于 100nm 的纳米粒子,并且检查了颗粒内存在的活性部分及其功能。非常有趣的是,已经表明可以有效地将生物素分子引入纳米粒子的表面,其中(理论量的 75%)可以与亲和素结合。有人提出,这种策略提供了一种可能性,可以通过使用众所周知的生物素-亲和素三明治技术,用各种识别配体轻松修饰这些纳米粒子,以实现特定靶向应用。