| Poly(s-caprolactone) is a biocompatible degradable aliphatic polyester, and widely used in biomedical and pharmaceutical fields. However, the absence of suitable cationic functional groups and its strong hydrophobicity limit its use in negative drugs and gene delivery. Therefore, the synthesis of hydrophilic poly(s-caprolactone) with cationic pendant groups has attracted great interests. In this paper, amino groups were introduced to the backbone of poly(s-caprolactone), which endows poly(ε-caprolactone) with cationic functional groups and hydrophility and broaden its application in hydrophilic negative drugs and gene delivery system.The main contents of this paper are summarized as follow:1. A series of methoxy poly(ethylene glycol)-b-poly(y-amino-s-caprolactone) (mPEG-b-PACL) copolymers with different chemical compositions were synthesized by ring opening copolymerization of CABCL initiated by the hydroxyl group of methoxy poly(ethylene glycol) using stannous octoate as the catalyst, followed by the removal of the protected groups. The structure and molecular weight of the copolymer were confirmed by 1H NMR, FT-IR and GPC, respectively. Differential scanning calorimetry (DSC), Thermal Gravimetric Analysis (TGA) and Wide Angle X-ray diffraction (WAXD) were used to study the thermal properties and crystallinity of the copolymers.2. The aqueous solution properties of mPEG-b-PACL copolymers as a function of pH have been studied using dynamic lights scattering (DLS), aqueous electrophoresis, hydrogen ion titration and transmission electron microscopy (TEM), respectively. The results demonstrated that mPEG-b-PACL copolymer exhibited a rich pH-responsive behavior with an appropriate PACL length. They were double hydrophilic copolymers below a critical PACL length. While well-defined aggregates were formed that consist of a PACL core surrounded by an uncharged mPEG shell chain beyond a critical PACL length.3. A series of ammonium glycyrrhizinate-loaded nanoparticles were prepared by electrostatic interaction between positively charged PACL and negatively charged AMG at a certain pH value. Two kinds of complex methods were adopted during the process based on the chain length-dependence properties of mPEG-b-PACL. Turbidity method and fluorescence spectrometry were employed to study the formation process of the drug-loaded nanoparticles. FT-IR was used to study the structure of the drug-loaded nanoparticles. TEM and aqueous electrophoresis were used to investigate the morphology, particles size and surface charges of the nanoparticles, respectively.The drug loading capacity (DLC) and encapsulation efficiency (EE) were investigated at different polymer compositions and WPACL/WAMG. The in vitro drug release profiles of AMG-PACL nanoparticles were obtained to evaluate their potential as drug delivery system. The results suggested that the AMG-PACL nanoparticles system might be used to provide continuous release.4. HepG2 cells were used as the model of normal liver cells to investigate the effect of AMG-loaded nanoparticles to prevent liver cells from apoptosis induced by Lipoplysaccharide (LPS). Albumin and lactate dehydrogenase secretion of HepG2 cells cultured with different samples were evaluated. The results showed that the PACL-AMG nanoparticles could inprove the albumin secretion and reduce the lactate dehydrogenase secretion. Fluorescence microscopy was used to investigate the mitochondrial changes involved in the HepG2 cells treated with different culture medium. PACL-AMG nanoparticles could prevent liver cell from apoptosis induced by LPS based on the cells apoptosis assay by flow cytometry. Thus, it was expected that the biodegaradable mPEG-b-PACL represented a potential carrier for delivering water-soluble anion drugs or gene. |
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