三嵌段共聚物在药学研究中的应用进展

摘要

In recent years, amphiphilic block copolymers as important drug carriers were widely applied in drug reseach. They possess amphipathic properties, good biocompatibility and biodegradability. And they can self-assembly into core-shell structures and exhibit prolonged systemic circulation times and reduced uptake by the reticulo-endothelium system (RES). These materials, when intended for use in drug delivery, are generally composed of biocompatible, biodegradable hydrophobic polymer blocks such as polyesters or poly(amino acids) covalently bonded to a biocompatible hydrophilic block, typically PEG. As the ratio of the molecular weights of the hydrophilic and hydrophobic blocks changes, the morphologies and physicochemical properties will be correspondingly altered. Their utility in the field of drug delivery is based on their characteristic self-assembly into core-shell structures in aqueous solution. The hydrophilic blocks of the copolymer form the outer shell, while the hydrophobic blocks form the inner core. This core-shell structure provides a loading space to accommodate mainly hydrophobic drugs. This was repeatedly demonstrated for a broad variety of drugs, mostly poorly soluble anti-cancer drugs and can enhance drug stability, increase drug solubility, and improve transport properties of pharmaceutical molecules. So amphiphilic block copolymers have attracted a great deal of attention because of their properties. This review presents the classification and applications of triblock copolymers such as micelles, nanoparticles, microspheres, hydrogels, emulsion, nanoreactors in drug research. First of all, triblock copolymers can be classified into two types according to the composition, ABA and ABC. They have different aggregation morphology, such as spheres, rods, vesicles, lamellae, hamburger, wormlike and several others. Then their applications in pharmaceutical field are very important. A range of triblock copolymers have been developed for various applications. For instance, triBlock copolymer micelles have a whole set of unique properties, such as small sizes, narrow particle size distribution, a core-shell architecture, a good thermodynamic stability in physiological conditions, high drug loading capacities and targeting the drugs to specific sites in a passive way or attaching ligands in an active way; Triblock copolymer hydrogels have been developed as stimuli-responsive materials, which can undergo volume changes in response to changes in temperature, pH, and antigen, and they can provide a protective environment and allow control of diffusion of drugs by adjusting the crosslinking densities; Nanoparticulate drug delivery systems composed of triblock copolymers have been extensively explored due to the many advantages they provide such as prolonged circulation, passive targeting and enhanced solubilization of hydrophobic drugs; Triblock copolymeric nanoreactors are introduced as an alternative for liposomes as encapsulating carrier for prodrug activating enzymes, and so on. To still further their performance, all these drug carriers can be made slowly biodegradable, stimuli-reactive (pH- or temperature-sensitive), and targeted (by conjugating them with ligands specific towards certain characteristic components of the pathological area). Apart from these, the conjugation of a drug to an triblock polymer and the mixed system of two triblock copolymers are also good methods. Of cause, there are also many obstacles which researchers are trying their best to overcome. For example, protein and peptide drugs have high molecular weight and sensitive spatial structure, the associated controlled release technique is rather challenging. So how to tailer parameters of triblock copolymers for final application become a subject of interest.