Preparation Of Polymer-camptothecin Conjugate Nanomicelle For Enhanced Solubility And Stability Of Camptothecin

Polymer nanoparticles are used as carriers for the delivery of drug. It has been one of the most attractive areas because of its scientific value and potential of application. There is a need to design efficient synthetic methods to obtain polymer conjugates with drug and other bioactive components. Nanoparticles prepared from synthetic or natural polymers have applications in various technological and biomedical fields, because their chemical structures, surface functionalities, and particle size can be easily controlled. Nanoparticles can be defined as colloidal systems with a diameter smaller than 1000 nm. Recently, self-assembling block copolymers or hydrophobically modified polymers have been extensively investigated in the field of biotechnology and pharmaceuticals. Amphiphilic block or graft copolymers form self-assembled, nano-sized micelle-like aggregates of various morphologies in aqueous solution. In general, self-assembled nanoparticles are composed of an inner hydrophobic core and an outer shell of hydrophilic groups. Hydrophobic blocks form the inner core of the structure, which act as a drug incorporation site, especially for hydrophobic drugs. Hydrophobic drugs can thus be easily entrapped within the inner core by hydrophobic interactions. These self-aggregating characteristics of the polymers have attracted considerable attention as effective targetable drug carriers, for example polyion complex micelles and hydrophobized polysaccharides. We design preparation of polymer-CPT conjugates in order to enhance the solubility and stability of CPT.Chapter 1:IntroductionPolymeric nanoparticles are of especial interest from the pharmaceutical point of view. First they are more stable in the gastrointestinal tract than other colloidal carriers, such as liposomes, and can protect encapsulated drugs from gastrointestinal environment. Second, the use of various polymeric materials enable the modulation of physicochemical characteristics, drug release properties, and biological behavior of nanoparticles. Finally, the particle surface can be modified by adsorption or chemical grafting of certain molecules such as poly(ethylene glycol) (PEG), poloxamers, and bioactive molecules (lectins, invasins,). Moreover, their submicron size and their large specific surface area favor their absorption compared to larger carriers.Chapter 2:Synthesis and in vitro cytotoxicity of polymer-CPTIn this chapter, polymer carrier:With the aid of water/triethylamine as solvent, a,β-poly [(N-carboxybutyl)-L-aspartamide](PBAsp) was successfully synthesized by ring cleavage reaction of L-asprtic acid to polysuccinmide in a homogeneous system at room temperature. PBAsp-CPT conjugates were synthesized by the esterification between PBAsp and 20-OH of CPT. The copolymers form micelle by self-assembly and their structures were examinsed by Nuclear Magnetic Resonance(NMR) and (FT-IR).Chapter 3:Synthesis and characteristic of solubiliry polymer-CPT prodrugWe have developed a solubility polymer-CPT nanoparticles with "click" cycloaddition. The copper(Ⅰ)-catalyzed 1,2,3-triazole formation from azides and terminal acetylenes is a particularly powerful linking reaction, due to its high degree of dependability, complete specificity, and the biocompatibility of the reactants. The triazole products are more than just passive linkers; they readily associate with biological targets, through hydrogen bonding and dipole interactions. Its applications are increasingly found in all aspects of drug discovery, ranging from lead finding through combinatorial chemistry and target-templated in situ chemistry.