Preparation And Characterization Of Polymeric Nanoparticles And Their Primary Application As Drug Carriers

Drug delivery system has developed greatly in recent years due to the nano techno logy. There are many routes to fabricate polymeric nanoparticles. Self-assembly has attracted great attention because the size of the nanoparticles and the drug release behavior can be controlled by the composition and structure of the copolymers. Driven by the requirements in biological and medicine science, the preparation of biocompatible, biodegradable and targeted drug delivery system became the new developing orientations. Catering to the developing trend, the research work in this thesis was focused on the synthesis, characterization and primary application of the nanoparticles for drug delivery. Specially, five sections of work were carried as follows:(1) The amphiphilic diblock copolymers (MePEG-PLA) based on methoxy poly (ethylene glycol) and d,l-lactide were synthesized using stannous octoate as catalyst. MePEG-PLA copolymers were self-assembled into nanoparticles with core-shell structures. The structures were further identified by 1HNMR. Pyrene, a fluorescent probe, was encapsulated into the nanoparticles by dialysis used as model drug. The particle size, zeta potential and pyrene loading efficiency of MePEG-PLA nanoparticles were dependent on the PLA block content in the copolymers. Following nasal administration, the results obtained by fluorescence microscopy indicated that olfactory mucosa appeared to be more permeable for nanoparticles and the olfactory epitheilial pathway was to be used to transfer nanoparticles from nasal cavity to the olfactory bulb, and MePEG-PLA nanoparticles might have a great potential as carriers of hydrophobic drugs.(2) The copolymers of methoxy-PEG-PLA and maleimide-PEG-PLA were synthesized by ring opening polymerization of D, L-lactide initiated by methoxy-PEG and maleimide-PEG, respectively, which were applied to prepare pegylated nanoparticles by means of double-emulsion and solvent evaporation procedure.Native bovine serum albumin (BSA) was cationized and thiolated, followed by conjugation through the maleimide function located at the distal end of PEG surrounding the nanoparticle's surface. Surface nitrogen was detected by X-ray photoelectron spectroscopy (XPS), which proved that CBSA was covalently conjugated onto its surface. The size and the morphology of the nanoparticles were characterized by DLS and TEM. 6-coumarin was used as fluorescent label, the controlled release behavior was studied in pH=4 and 7.4. The results show that 6-coumarin could serve as useful fluorescent probe. 6-coumarin-loaded nanoparticles was injected in mice caudal vein. The results obtained by fluorescent microscopy show that cationic albumin could serve as useful control group, which could supply the experimental proofs for the brain drug delivery.(3) A series of amphiphilic copolymers of methoxy-poly(ethylene glycol)-polycaprolactone (MePEG-PCL) were by using stannous octoate as catalyst. FTIR, NMR, GPC, TGA, DSC, XRD were used to confirm the structures of the copolymers. The monodisperse copolymeric nanoparticles were prepared by dialysis, and their diameters increased with the PCL content and the hydrophobic chain length. Hydroxycamptothecin (HCPT) as a model drug was entrapped in the nanoparticles by solid-dispersion and dialysis-hydration method, span 60 was used to enhance the compatibility between the drug and copolymers. The drug loading efficiency depends on the ratio of PCL in the copolymers and the molecular weight of the copolymers. The in vitro drug release results indicated that the release behavior could be controlled by the composition of the copolymers, and the half time of the nanoparticles in the blood depend on the length of PEG on the surfaces of nanoparticles, the longer the PEG, the longer the half time of the nanoparticles had.(4) Biodegradable tri-component diblock copolymer was synthesized by bulk copolymerization of e-caprolactone (CL) and D, L-lactide(LA) in the presence of methoxy poly (ethylene glycol)(MePEG), using stannous octoate as catalyst. Their chemical structure and physical properties were investigated by GPC, NMR, DSC,...