李孝红
可生物降解聚合物及药物控制释放体系
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- 姓名:李孝红
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学术头衔:
博士生导师
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学科领域:
光学
- 研究兴趣:可生物降解聚合物及药物控制释放体系
李孝红,1969年生。1999年于中科院化学所获化学博士学位,研究方向是可生物降解聚合物及药物控制释放体系。1999起作为项目组成员参与国家973项目“用于基因和抗癌药物控制释放高分子材料的研究” (G1999064703)的研究工作,作为负责人主持承担了中科院应用研究与发展重大项目“公斤级聚氨基酸的工艺放大实验”、国家自然科学基金“可生物降解聚合物作为基因控制释放载体的研究”(20004009)。2000年至2004年先后在美国Ohio State University药学院和Johns Hopkins University生物医学工程系从事生物材料和药物控制释放体系的研究工作。目前已发表论文43篇,发明专利1项,其中在SCI收录杂志上发表28篇,已被引用150余次。现为美国癌症研究学会、美国药学科学家协会、美国基因治疗学会、中国生物材料学会会员,担任Biomacromolecules, Journal of Pharmacy and Pharmacology论文评审人。
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李孝红 , Shaobing Zhou, , Xianmo Deng, Xiaohong Li, Wenxiang Jia, Li Liu
Journal of Applied Polymer Science, Vol. 91, 1848-1856 (2004),-0001,():
-1年11月30日
Poly(lactic acid) (PLA) and poly(lactic-co- GA) (PLGA) with low molecular weights were synthesized by a one-step polycondensation of lactic acid (LA) with glycolic acid (GA) molecules using stannous octoate as a catalyst at 160℃. A high yield (80%) of all the polymers was obtained in the study. The PLA and PLGA copolymers were characterized by 1H-NMR, GPC, and DSC measurements, etc. We elaborated HSA-loaded microspheres based on PLA and PLGA copolymers with different monomer ratios (LA/GA -85:15, 75:25, 65:35, and 50:50) by the solvent-extraction method based on the formation of double w/o/w emulsion. Microspheres were characterized in terms of the morphology, size, and encapsulation efficiency (E.E.). The highest E.E. (69.3%) of HSA was obtained for HSAloaded PLGA (65/35) microspheres among all the formulations. In vitro matrix degradation and protein release of these microspheres were performed in phosphate-buffer saline (PBS; 154mM, pH 7.4). The degradation profiles were characterized by measuring the loss of the microsphere mass and the decrease of the polymer intrinsic viscosity. The release profiles were investigated from the measurement of the protein presented in the release medium at various intervals. It was shown that the matrix degradation and protein-release profiles were highly LA/GA ratio-dependent. It is suggested that these matrix polymers may be optimized as carriers in protein- and peptide-delivery systems for different purposes.
biodegradable, polyesters, proteins
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李孝红 , Shaobing Zhou, *, Xueyan Liao, , Zhenglun Liang, Xiaohong Li, Xianmo Deng, Heming Li
Macromol. Biosci. 2004, 4, 47-52,-0001,():
-1年11月30日
antigen, biodegradable, drug delivery system, microspheres
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李孝红 , XIAOHONG LI, , SHAOBING ZHOU, XIAORONG WU, MINGLONG YUAN, LI LIU, WENXIANG JIA, XIANMO DENG, ZHITANG HUANG
Journal of Applied Polymer Science, Vol. 83, 850-856 (2002),-0001,():
-1年11月30日
This project was aimed at illustrating the potential use of poly-DL-lactidepoly(ethylene glycol) (PELA) microspheres as a hepatitis B surface antigen (HBsAg) delivery system following subcutaneous (s.c.) or oral immunization over the current injection of an alum-absorbed antigen. The antigen-loading microspheres were elaborated by the solvent-extraction method based on the formation of modified multiple w/o/w emulsion. The microspheres were characterized by their particle size, HBsAg entrapment, and in vitro HBsAg release behavior. Balb/c mice were immunized with an s.c. injection and oral administration of a single dose and two doses of a microsphere formulation. For comparison, the alum-absorbed HBsAg-immunized mice had a following intramuscular (i.m.) injection at weeks 0 and 4. At weeks 8, 10, 14, and 24 postadministration, the blood and saliva samples were collected and detected by the enzyme-linked immunosorbed assay (ELISA) method. A single injection of HBsAg/ PELA microspheres could induce a serum lgG antibody level comparable to the twoinjection alum-absorbed HBsAg at the 14th week and higher than that at the 24th week. The saliva lgA of peroral groups was significantly higher than that of the s.c. injection of a microsphere formulation and i.m. injection of soluble antigen. Thesepreliminary results demonstrated the potential of oral administration of antigenloading microspheres in the induction of a secretory immune response, and it is suggested that a single-dose s.c. injection of antigen-loading microspheres would be an efficient immunization schedule to elicit a protective response.
biodegradable, drug delivery systems, polyester, microencapsulation, protein
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【期刊论文】P oly-D,L-lactide-co-poly(ethylene glycol) microspheres as potential vaccine delivery systems
李孝红 , Shaobing Zhou a*, Xueyan Liao b, Xiaohong Li a, Xianmo Deng a, Heming Li b
Journal of Controlled Release 86(2003)195-205,-0001,():
-1年11月30日
aimed at increasing the immunogenicity of recombinant antigens remain a focus in vaccine development. Worldwide, there is currently considerable care for the development of biodegradable microspheres as controlled release of vaccines, since the major disadvantage of several currently available vaccines is the need for repeated administration. Microspheres prepared from the biodegradable and biocompatible polymers, the polylactide (PLA) or polylactide-coglycolide (PLGA), have been shown to be effective adjuvants for a number of antigens. This review mainly focuses on polylactide-co-poly(ethylene glycol) (PELA) microspheres adjuvant as vaccine delivery systems by summarizing our and other research groups' investigation on properties of the microspheres formulation encapsulating several kinds of antigens. The results indicate that compared with the commonly used PLA and PLGA, PELA showed several potentials in vaccine delivery systems, which may be due to the block copolymer have its capability to provide a biomaterial having a broad range of amphiphilic structure. PELA microspheres can control the rate of release of entrapped antigens and therefore, offer potential for the development of single-dose vaccines. The PELA microspheres have shown great potential as a next generation adjuvant to replace or complement existing aluminum salts for vaccine potential. The review mainly aims to promote the investigation of PELA microspheres adjuvant for antigens for worldwide researcher.
Microspheres, Controlled release, Polylactide-co-poly(, ethylene glycol), , Biodegradable polymers, Vaccine adjuvants, Single-dose vaccines
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【期刊论文】Investigation on a novel core-coated microspheres protein delivery system
李孝红 , Shaobing Zhou*, Xianmo Deng, Xiaohong Li
Journal of Controlled Release 75(2001)27-36,-0001,():
-1年11月30日
Among the different approaches to achieve protein delivery, the use of polymers, specifically biodegraded, holds great promise. In this work, a new microsphere delivery system composed of alginate microcores surrounded by a biodegradable poly-DL-lactide-poly (ethylene glycol (PELA) was designed to improve the loading efficiency and stability of proteins. Alginate was solidified by calcium (MS-1), polylysine (MS-2) and chitosan (MS-3), respectively, to form different microcores. Human Serum Albumin (HSA), used as a model protein, was efficiently entrapped within the alginate microcores using a high-speed stirrer and then microencapsulated into PELA copolymer using a w/o/w solvent extraction method. DSC analysis of the microspheres revealed the efficient encapsulation of the alginate microcores, while the microcores were dispersed in the PELA matrix. SDS-PAGE results showed that HSA kept its structural integrity during encapsulation and release procedure. Microspheres were characterized in terms of morphology, size, loading efficiency, in vitro degradation and protein release. The degradation profiles were characterized by measuring the loss of microsphere mass, the decrease of polymer intrinsic viscosity and the reduction of PEG content of PELA coat. The release profiles were investigated from the measurement of protein presented in the release medium at various intervals. The results were that the degradation rate of these core-coated microspheres was MS-2.MS-1.MS-3. The extent of burst release from the core-coated microspheres in the initial protein release was lower than the 27% burst release from the conventional microspheres. In conclusion, the work presents a new approach for macromolecular drugs (such as protein, peptide drugs) delivery. The core-coated microspheres system may have potential use as a carrier for drugs that are poorly absorbed after oral administration.
Core-coated, Biodegradable microspheres, Alginate, In vitro, Poly-DL-lactide-poly(, ethylene glycol),
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李孝红 , Xiaohong Li a, *, Yanhua Zhang b, Ronghua Yan b, Wenxiang Jia b, Minglong Yuan a, Xianmo Deng a, Zhitang Huang c
Journal of Controlled Release 68(2000)41-52,-0001,():
-1年11月30日
Glucose oxidase (GOD) has been encapsulated as a model protein within poly-DL-lactide-poly(ethylene glycol) (PELA) microspheres to evaluate the activity retention during microencapsulation process. This paper was aimed to investigate the effect of process parameters, such as the preparation method, the used matrix polymer with different compositions, the solvent system and the addition of stabilizer on the structural integrity and activity retention of encapsulated protein. The stability of the protein released during in vitro assay was also assessed. The obtained results showed that the solvent extraction/evaporation method based on the formation of double emulsion w/o/w benefited the activity retention 1 2 compared with the phase separation method based on the formation of w/o/o. And in the emulsion-evaporation system 1 2 most of the protein activity was lost during the first emulsification procedure to form primary emulsion w/o(ca. 28%) and 1 the second emulsification procedure to form the double emulsion w/o/w (ca. 20%), in contrast to other processes 1 2 occurring during microspheres preparation. The matrix polymer and the solvent system in the oil phase had an impressive impact on the activity retention, while the addition of gelatin in the internal aqueous phase resulted in no major reduction of activity loss. GOD release from PELA microspheres exhibited a triphasic profile, that is, the initial burst release during the first day, the gradual release over about 1 month, and then the second burst release. The encapsulation of GOD in PELA microspheres was effective in reducing its specific activity loss. Sixty-seven per cent of the initial specific activity retention was detected for the released GOD from microspheres formulation during 1 week of incubation, but nearly all the activity was lost for GOD in solution incubated under the same condition. SDS-PAGE results showed that, although the activity loss was detected, no rough changes of molecular weight of GOD was observed during encapsulation procedure and the initial days of incubation into the in vitro release medium.
Poly-DL-lactide-poly(, ethylene glycol), , Glucose oxidase, Activity retention, Microencapsulation, Process parameters, In vitro release
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李孝红
,-0001,():
-1年11月30日
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李孝红 , XIAOHONG LI, , XIANMO DENG, MINGLONG YUAN, CHENGDONG XIONG, ZHITANG HUANG, YANHUA ZHANG, WENXIANG JIA
Journal of Applied Polymer Science, Vol. 78, 140-148 (2000),-0001,():
-1年11月30日
Poly-DL-lactide (PLA) and poly-DL-lactide-poly(ethylene glycol) (PELA) were produced by bulk ring-opening polymerization using stannous chloride as initiator. PLA, PELA microspheres, and PELA microspheres containing the outer membrane protein (OMP) of Leptospira interrogans with the size of 1.5-2mm were prepared by a solvent evaporation process. In vitro degradation and release tests of PLA, PELA, and OMP-loaded PELA microspheres were performed in pH 7.4 buffer solution at 37
poly-DL-lactide-poly(, ethylene glycol), , degradation, degradation mechanism, protein release, release mechanism
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李孝红 , Xianmo Deng*, Shaobing Zhou, Xiaohong Li, Jing Zhao, Minglong Yuan
Journal of Controlled Release 71(2001)165-173,-0001,():
-1年11月30日
Poly-dl-lactide-poly(ethylene glycol) (PELA) block copolymers containing same the content (10%) of polyethylene glycol (PEG) were synthesized with five different molecular weight of PEG by ring-opening polymerization. PELA microspheres containing human serum albumin (HSA) were elaborated by solvent extraction method based on the formation of double w/o/w emulsion. In vitro matrix degradation and protein release of these microspheres were performed in hosphatebuffered saline (PBS) (154mM, pH 7.43). The degradation profiles were characterized by measuring the loss of microspheres mass, the decrease of polymer intrinsic viscosity, the decrease of pH value of degradation medium, the reduction of polymer number-average molecular weight (M) and the change of molecular weight polydispersity (M/M). n w n The release profiles were investigated from the measurement of protein presented in the release medium at various intervals. It showed that the matrix degradation and protein release profiles were highly polymer-dependent. The extent of burst release in the initial protein release increased with the decrease of molecular weight of PELA copolymer. It is suggested that these matrix polymers may be optimized as carriers in protein (antigen) delivery system for different purposes.
Poly-dl-lactide-poly(, ethylene glycol), (, PELA), , Microspheres, Protein release, Polymer degradation
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李孝红 , XIAOHONG LI, YANHUA ZHANG*, RONGHUA YAN*, MIN ZHANG*, MINGLONG YUAN, XIANMO DENG, AND ZHITANG HUANG†
J. Pharm. Pharmacol. 2000, 52: 763-770,-0001,():
-1年11月30日
Poly-DL-lactide-poly (ethylene glycol) (PELA) microspheres with entrapped antigens were administered intravenously and orally into guinea-pigs to quantitatively determine the in-vivo distribution and release profiles. PELA microspheres containing 125I-labelled outer-membrane protein Leptospira inter-rogans antigens (125I-OMP) were prepared by double-emulsion solvent extraction procedure, and characterized with respect to size, morphology and in-vitro release profiles. The fractured sections of liver and spleen were inspected by scanning electron microscopy, which indicated that microspheres had successfully been entrapped within the above tissues after intravenous injection and oral administration. At predetermined intervals, the blood and such tissues as the liver, spleen, kidney, thyroid, small intestine and mesentery were collected, and the radioactivity was measured by gamma scintillation counting. Following intravenous administration, 56.7% of administered microspheres were accumulated in immunization-related tissues, and 40.1% of microspheres were located in the liver and spleen. However, there was limited uptake efficiency (8-33%) following oral administration, and 49.5% of the absorbed microspheres were located in the intestinal mucosa. Compared with in-vitro release, the in-vivo release profiles of 125I-OMP from PELA microspheres, determined from the decreasing radioactivity in the above tissues, were much faster and the burst effect was higher. Antigen-loaded PELA microspheres were efficiently entrapped within immunization-related tissues after intravenous administration, but orally administered PELA micro-spheres showed limited uptake efficiency. Further investigation is needed to improve intestinal absorption.
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