Advanced Biomaterials VI

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Authors: T. Kushibiki, K. Matsumoto, T. Nakamura, Yasuhiko Tabata
Abstract: NK4, composed of the NH2-terminal hairpin and subsequent four-kringle domains of hepatocyte growth factor (HGF), acts as a potent angiogenesis inhibitor. This study is an investigation to evaluate the feasibility of controlled release of NK4 plasmid DNA in suppressing tumor growth. Controlled release by a biodegradable hydrogel enabled the NK4 plasmid DNA to enhance the tumor suppression effects. Biodegradable microspheres of cationized gelatin were prepared for the controlled release of a NK4 plasmid DNA. The cationized gelatin microspheres incorporating NK4 plasmid DNA were subcutaneously injected to tumor-bearing mice to evaluate the suppressive effects on tumor angiogenesis and growth. The cationized gelatin microspheres incorporating NK4 plasmid DNA could release over 28 days. When the cationized gelatin microspheres incorporating NK4 plasmid DNA were injected into the subcutaneous tissue of mice intraperitoneally inoculated with pancreatic cancer cells, their survival time period was prolonged. Tumor growth was suppressed to a significantly greater extent than free NK4 plasmid DNA. The controlled release of NK4 plasmid DNA suppressed angiogenesis and increased cell apoptosis in the tumor tissue, while it enhanced and prolonged the serum level of NK4 protein. We conclude that the controlled release technology was promising to enhance the tumor suppression effects of NK4 plasmid DNA.
Authors: Shen Guo Wang, Qing Cai, Jian Zhong Bei, Wei Yun Shi, Li Xin Xie
Abstract: In the article a kind biodegradable drug carrier (glycolide-co-lactide-co-caprolactone) tricomponent copolymer (PGLC) was synthesized by ring opening copolymerization of glycolide (GA), lactide (LA) and ε-caprolactone (CL), and was used to manufacture an implantable drug preparation---Cyclosporine-PGLC drug delivery system (Cs-PGLC DDS).The Cs could slowly release from the Cs-PGLC DDS near linearly and last for a long time in vitro. A clinically significant Cs concentration in the cornea and anterior chamber could be achieved by implanting the Cs-PGLC DDS in anterior chamber. It was demonstrated that the Cs-PGLC DDS is a long-effective intraocular immunosuppressive agent for remaining corneal allograft clear and significantly prolong its survival time.
Authors: Ling Chen, Xiao Xi Li, Lin Li, Bing Li
Abstract: Colon-targeting drug delivery systems (CDDSs) are employed to improve the bioavailability of protein and peptide drugs through the oral route. So it is important to prepare the drug carriers for oral CDDS. In this study, the Enzyme-Resistant starch (RS) was studied for use as a vehicle in oral colon-targeting drug delivery. The characteristics of RS powders were investigated by X-ray diffraction, polarizing microscopy, DSC and SEM, and their film were examined by enzymatic digestion test. The results showed that RS could be a promising film-former for pharmaceutical coatings, having good stability to enzymatic digestion. Furthermore, a novel peroral formulation using RS coating and bovine serum albumin as a model drug was studied for colon-specific drug delivery in vitro. Drug release studies have shown that RS coating could delivery the drug to the colon and the release rate in simulated colonic fluids was dependent on the biodegradation of RS and its coatings. It is indicated that the RS coated tablet is a potential system for oral CDDS.
Authors: Makoto Ozeki, Yasuhiko Tabata
Abstract: This study is an investigation to evaluate how the controlled release of different growth factors affects the hair follicle growth of mice in the second anagen stage of hair cycle. For the controlled release of basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF), they were incorporating into biodegradable gelatin hydrogels, while a biodegradable collagen hydrogel was used for incorporation of vascular endothelial growth factor (VEGF). After subcutaneous implantation of the different hydrogels incorporating each growth factor or injection of phosphate buffered saline (PBS) containing the same dose of growth factor into the back of mice, the hair follicle growth was evaluated photometrically and histologically based on four parameters: the skin color of reverse side of the implanted or injected site, the number of vessels newly formed, the area occupied by hair follicle tissue, and the hair length. The area in close proximity to the implanted site of hydrogels incorporating growth factor was still dark in color 10 days after application. The hydrogel incorporating any type of growth factor enabled the hair follicles to increase the size, leading significantly enhanced area occupied by hair follicles per unit area of tissue. Implantation of the hydrogels incorporating growth factor increased significantly the number of blood vessels newly formed. Moreover, the length of hair shaft was elongated by the hydrogel incorporating growth factor to a significantly higher extent than the corresponding growth factor. Neither empty gelatin nor collagen hydrogels affected the hair follicle growth. These results indicate that the hydrogel incorporating growth factor induced the anagen-preservable activity. We conclude that the controlled release enabled growth factors to positively act on the hair growth cycle of mice, irrespective of the factor type.
Authors: Xian Tao Wen, Hong Song Fan, Yan Fei Tan, H.D. Cao, H. Li, B. Cai, Xing Dong Zhang
Abstract: A electrospinning process to prepare soft tissue engineering scaffold was introduced in this study. This kind of scaffold was composed with ultrathin fiber and characterized with high porosity, well-interconnected pores and high surface-to-volume ratio. Biodegradable polylaticacid (PLA) was used to spin the scaffold and the scaffold was evaluated in vitro by analysis the microscopic structure, porosity, mechanical property, especially cytocompatibility. The results indicated that the electrospun PLA scaffold showed good cytocompatibility and the tensile property of electrospun scaffold was similar to human’s soft tissue. It could be expected that the electrospun scaffold would be potential in soft tissue engineering or soft tissue repair.
Authors: Jing Yang, Cun Xian Song, Hong Fan Sun, Li Wu, Lina Tang, Yong Zeng, Wen Ling Zhu
Abstract: A reporter gene pEGFP and a therapeutic antisense monocyte hemotactic protein-1 (MCP-1) gene were encapsulated into poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) using an emulsification / solvent evaporation technique. The gene-NPs were around 300 nm in diameter with very narrow size distribution. The encapsulation efficiency of DNA was significantly improved when poly (lysine) was used in cooperation with DNA. The NPs demonstrated a steady in vitro release of DNA with more that 95% of total enclosed DNA released within 14 days. In cell culture, pEGFP -loaded NPs were able to express in smooth muscle cells at a level same as that of Lipofectin induced plasmid. To observe the effects of antisense MCP-1 NPs on the inhibition of restenosis, balloon catheter-induced injury was used to establish an intimal hyperplasia model of rabbit carotid artery. Antisense MCP-1 expression was confirmed in the artery tissue with local delivery of the therapeutic NP into the injured artery. Intima/media ratio of arteries treated with the antisense NPs was reduced by 43% compared with control group. In conclusion, NP could be an effective gene carrier for intravascular site-specific gene therapy.
Authors: Yun Xiang Hu, Jin Chang, Yi Guo, Xu Bo Yuan, Chun Sheng Kang, Peiyu Pu
Abstract: In this study, we constructed a novel drug delivery system for realizing the combination of gene therapy and chemotherapy by co-loading 5-FU and antisense EGFR (epidermal growth factor receptor) plasmids in biodegradable PLGA/O-CMC (O-carboxmethyl-chitosan) nanoparticles. This novel kind of nanoparticle was characterized by dynamic light scattering for size, size distribution and zeta potential, and scanning electron microscopy (SEM) and transmission electronic microscopy (TEM) for morphological properties and structures. Drug encapsulation efficiency and drug release kinetics under in vitro conditions were also measured. At the same time, the MTT assay, the TUNEL technique and immunohistochemical staining were used to investigate the antitumor activity of these multi-functional nanoparticles on human glioma cells. It was concluded that the 5-FU and plasmid encapsulation efficiencies were as high as 94.5% and 95.7%, and the 5-FU release activity from nanoparticles could be sustained for as long as three weeks. Both the MTT assay and the TUNEL method illustrated that these multi-functional nanoparticles had cytotoxicities as high as 93.5% and could induce apoptosis in most glioma cells. Immunohistochemical staining proved that plasmids on the surface of nanoparticles could transfect gliomas cells, verified by a decline in the expression level of EGFR protein by the glioma cells. Therefore, this novel delivery system for drugs and genes provides another therapeutic pathway for cancer and needs further research.
Authors: Rui Rui Cao, Sheng Min Zhang, Q.M. Luo, X.H. Liang, J. Liu, W. Zhou
Abstract: The regular spherical poly-D, L-lactic acid (PDLLA) nanoparticles containing DNR are produced using a double-emulsion solvent evaporation process. The products morphology is characterized by a laser light-scattering particle size analyzer and scanning electron microscopy. Results show a mean diameter in 546.9 nm with narrow size distribution and homogeneous particle production. The encapsulation efficiency is evaluated by UV spectra. The results indicate that drug contents and loading efficiency are 14.34% and 72.9% respectively, and the drug release profile shows a biphasic phenomenon.
Authors: Yong Zhang, J. Zhang
Abstract: Targeting of drugs and therapeutic materials to target cells or designated intracellular locations relies upon their cellular / sub-cellular targeting and trafficking. The ideal optical properties of quantum dots offer the possibility of using them as fluorescent probes to study the intracellular uptake and pathway of drugs or biomolecules. Quantum dots, ZnS coated CdSe, were synthesized and successfully incorporated into polystyrene (PS) particles grafted with carboxyl groups and folic acid was attached to the nanoparticle surfaces. The nanocomposites were monodisperse and highly luminescent, and their intracellular uptake to cancer cells was investigated using confocal microscopy.
Authors: Toshiyuki Ikoma, N. Azuma, Shigeru Itoh, H. Omi, S. Nishikawa, Satoshi Toh, M. Tanaka
Abstract: Nanocomposites of hydroxyapatite / chondroitin sulfate or hyaluronic acid were prepared by a wet method through a self-organization. In the nanocomposites, the c-axis of hydroxyapatite nanocrystals was oriented along the longitudinal axis of the aggregations. The spherical porous microparticles by using a spray drying method were developed with the size range of 1.0 to 20 µm, specific surface area of c.a. 100 m2g-1 and porosities of over 60vol%. No thermal decomposition of polysaccharides was occurred through the spray drying processes. It is note worth that the zeta-potential of the microparticles were gradually changed to be negative value of -35mV against the content of polysaccharides. The animal experiments implanted under the skin showed that the HAp/ChS had a good biocompatibility for 4 week implantations. The spherical microparticles will be applicable to create more complicated composites and drug carriers.

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