Methods for efficient preparation of drug-polymer (or oligomer) conjugates which are useful in the preparation of particles, including microparticles and nanoparticles, for delivery of the drug in vivo for therapeutic applications. The invention additionally provides certain drug-polymer and drug-oligomer conjugates which are useful in the preparation of particles for delivery of the drug in vivo. The invention also provides nanoparticles of this invention prepared by nanoprecipitation using drug-polymer/oligomer conjugates of the invention.
The drug conjugates are formed during polymerization of the polymer or oligomer in which the drug is employed as an initiator of the polymerization of the monomers which form the polymer and/or oligomer. More specifically, the drug conjugates are formed by ring-opening polymerization of cyclic monomers in the presence of an appropriate ring-opening polymerization catalyst and the initiator (the drug). The method is particularly useful for formation of polymer/oligomer conjugates with drugs and other chemical species containing one or more hydroxyl groups or thiol groups.
本发明提供了一种有效制备药物-聚合物(或寡聚物)共轭物的方法,该方法可用于制备微粒和纳米粒子,以在体内传递药物进行治疗应用。本发明还提供了某些药物-聚合物和药物-寡聚物共轭物,该共轭物可用于制备体内药物传递的微粒。本发明还提供了通过使用本发明的药物-聚合物/寡聚物共轭物制备的纳米粒子。药物共轭物是在聚合物或寡聚物的聚合过程中形成的,其中药物被用作引发单体聚合形成聚合物和/或寡聚物的
引发剂。更具体地说,药物共轭物是通过在适当的开环聚合催化剂和
引发剂(药物)的存在下开环聚合环状单体形成的。该方法特别适用于与含有一个或多个羟基或
硫醇基团的药物和其他
化学物质形成聚合物/寡聚物共轭物。