Study On Preparation And Properties Of Macromolecular Nanoparticles

Regarded as an important way to realize the modernization of the pharmaceutics, nanocarriers are colloidal systems with the sizes between 10 ~ 1000 nm, especially below 500 nm, used to incorperate or absorb drugs, with which those loaded drugs may be accurately delivered in body. Featured with plentiful matrices for choosing, multiple methods for preparing and good stability, macromolecular nanoparticles are generally used nanocarriers. Focused on preparation and properties of macromolecular nanoparticles, systemic works were carried out in the dissertation. Based on coacervation technique and nanoprecipitation technique, a new technique named salting-out nanoprecipitation technique were proposed to prepare the triptolide-bovine serum albumin nanoparticles (TRD-BSA NPs), which broke out the "bottle-neck"that nanoprecipitation technique was only suitable to prepare lipophilic macromolecular carriers. Compared with other TRD-loaded nanocarriers, TRD-BSA NPs are characterized with higher drug loading and encapsulation efficacy and slower release: the highest drug loading, 25 %, encapsulation efficacy, not lower than 97.3 %, the longest release time, one week, average sizes, 239.5 ~ 581.5 nm,polydispersion index (P. D. I), 0.174 ~ 0.394 and zeta-potential, -18 ~ -5.07 mV. The degree of cross-linking, drug loading, production ratio, average size, P. D. I, zeta-potential, and release behavior of TRD-BSA NPs are affected by the added amount of TRD and the cross-linking time. Drug loading, production ratio and encapsulation efficacy of TRD-BSA NPs prepared from neutral saturated (NH4)2SO4 solutions are close to those of TRD-BSA NPs prepared from acidic saturated (NH4)2SO4 solutions, while both average size and P. D. I of the former are higher than those of the latter and zeta-potential of the former is more positive as well. The properties of TRD-BSA NPs suggest that the dispersion of TRD in TRD-BSA NPs is a kind of molecular dispersion; the out layer of TRD-BSA NPs is a TRD rich area, while the core is a TRD poor area. To avoid strong mechanical action and poison solvents, nuclear factor-kappa B decoy oligodeoxyribonucleotides (NF-κB decoy ODNs) were modified with the cationic surfactant to improve the lipophile, NF-κB decoy ODNs loaded polylactic acid nanoparticles (NF-κB decoy ODNs PLA NPs) were then prepared with nanoprecipitation process. Through this way nanoprecipitation technique may be used to carry hydrophilic macromolecular dugs. The properties of NF-κB decoy ODNs PLA NPs were characterized as below: the highest drug loading, 0.693 %, encapsulation efficacy, 22.64 ~ 56.84 %, production ratio, 65.3~85.1 %, average sizes, 255 ~ 409 nm, P. D. I, 0.024 ~ 0.0790 and zeta-potential, -1.246 ~ 0.5004, close to zero. Technical parameters, such as molecular weight of PLA, concentration of PVA in aqueous phase and concentration of PLA in organic phase, obviously influence the properties of NF-κB decoy ODNs PLA NPs, encapsulation efficacy, drug loading, production ratio, average size, P. D. I and zeta-potential, et al. The experiments suggest that NF-κB decoy ODNs PLA NPs may be formed with the flocculation-aggregation mechanism. Aimed to have a better understanding of the pungently disputed problems on the brain targeting of nanoparticles in an easy way, physical characterization was performed to feature the brain targeting of nanoparticles. Visible spectroscopic analyses and fluorescence spectroscopic analyses showed that a complex composed by the loading, T-80 and nanoparticles was found in the preparation of nanoparticles characterized with brain targeting. Fluorescence micoscopic analyses suggested being bound to nanoparticles that were overcoated by T-80 later, was necessary for the loading to be delivered to brain. Partial coverage was enough for T-80 coating to play a specific role in brain targeting. The specific role of T-80 coating on nanoparticles in brain targeting was thus confirmed. In order to help the observation with analytical electron microscopy (AEM), the copper chlorophyll a (CC) labeled PLA nanoparticles was prepared by a simple approach combining the nanoprecipitation method without surfactants with the dialysis method. According to visible diffuse reflectance spectra (DRS) and X-ray photoelectron spectroscopy (XPS), it is reasonable to deduce CC is aggregated in predominantly 6-coordinated state with interposition of water and entrapped in the polymeric matrix of nanoparticles, which may ensure the stable presence of CC in nanoparticles. AEM clearly showed that some nanoparticles were loacated at the wall of the microvasculum in brain, which supported the endocytosis mechanism together with the fluorescence micoscopicanalyses. AEM also showed some other nanoparticles were distributed around the microvasculum in brain, which suggested that some nanoparticles crossed the blood-brain barrier (BBB). This unreported discovery on brain targeting of nanoparticles may supply some proof on the mechanism of crossing BBB from the in vivo experiments.