Local administration of microtubule-targeting agent promote motor functional recovery after spinal cord injury in rats

Local administration of microtubule-targeting agent promote motor functional recovery after spinal cord injury in rats

e148 Abstracts / Journal of Controlled Release 259 (2017) e5–e195 [3] X.F. Hu, Z.H. Sheng, J.H. Yang, H.T. Wan, Fabrication of (heparin/chitosan oli...

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Abstracts / Journal of Controlled Release 259 (2017) e5–e195

[3] X.F. Hu, Z.H. Sheng, J.H. Yang, H.T. Wan, Fabrication of (heparin/chitosan oligosaccharides/ Pluronic) multilayer films via electrostatic layer-by-layer assembly, Acta Polym. Sin. 6 (2015) 650-656.

[2] S. Park, G.H. Kim, S.H. Park, J. Pai, D. Rathwell, J.Y. Park, Y.S. Kang, I. Shin, Probing cell-surface carbohydrate binding proteins with dual-modal glycan-conjugated nanoparticles, J. Am. Chem. Soc. 137 (2015) 5961-5968.

doi:10.1016/j.jconrel.2017.03.297

doi:10.1016/j.jconrel.2017.03.298

Specific-targeting thermometer of glycosylated porphyrin-cored dendrimers with siloxane- poly(amido amine) dendron-like arms for PDT to treat hepatoma

Local administration of microtubule-targeting agent promote motor functional recovery after spinal cord injury in rats

Xiaohui Dai⁎, Weihe Yang, Jiaming Hu, Wenli Yan Institute of Green Chemistry and Chemical Technology, Jiangsu University, Zhenjiang 212013, China ⁎Corresponding author. E-mail addresses: [email protected] (X. Dai), [email protected] (W. Yang) Glycoconjugated porphyrins have received increasing attention due to their potential biological application, such as anti-adhesins, drug delivery, imaging, nanomaterials and biosensors [1,2]. In this study, we fabricated a series of glycosylated porphyrin-cored dendrimers consisting of siloxane-poly(amido amine) dendron-like arms. It is known that silicon-blocks not only can enhance the stability but also change the interspace configuration which affects the photophysical properties of dendrimers. Firstly, siloxane-poly (amido amine) (Dm, m = 1, 2, 3) was used for initiating the controlled ring opening polymerization of monomer lactobionic acid, generating the dendron-like Dm-Lac (m = 1, 2, 3) possessing two, four, eight terminal glycosyl units, respectively. Then via click reaction of Dm-Lac with porphyrin a multifunctional specifictargeting thermometer of glycosylated porphyrin-cored dendrimers (PP-Si-PAMAM-Lac) was successfully fabricated. The glycosylated porphyrin dendrimers could not only specifically recognize the lectin, but also possess high fluorescence quantum yield and singlet oxygen production efficiency, mainly due to the terminal glycosyl moieties and the siloxane blocks. What’s more, the fluorescence intensity of these glycosylated porphyrin dendrimers decreased as the temperature increased. All the results demonstrated that these glycosylated porphyrin dendrimers could act as outstanding, specifictargeting and temperature-sensitive photosensitizers for photodynamic therapy (PDT) to treat hepatoma.

Xiaoling Li, Yuelong Wang, Liangxue Zhou, Gang Guo⁎ State Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China ⁎Corresponding author. E-mail address: [email protected] (G. Guo) Spinal cord injury (SCI) is a devastating traumatic event which can lead to a range of health problems beyond sensory and motor dysfunction. Moderate microtubule stability with low dose of Taxol® or epothilone B could reduce axon-inhibitory scarring while boost intrinsic axonal growth, and ultimately improve sensorimotor function after rodent SCI [1]. However, the microtubule-targeting agents are cytotoxic anti-cancer drugs with non-selectivity nature between normal tissue and the pathological site. Injectable hydrogel is especially compelling for treatment of SCI since the localized drug delivery system can decrease dose frequency and minimize systemic toxicity [2]. In the study, docetaxel loaded hydrogel composite (DOC-H) with biodegradability and thermosensitivity nature was fabricated for controlled drug delivery, its therapeutic activities and potential molecular mechanism to promote functional recovery were investigated on rats dorsal hemisection model. DOC-H exhibited a slow and sustained drug release profile in vitro. Meanwhile, DOC-H was a free flowing sol at room temperature, and after applied to the lesion site it became a solid-like gel as well as drug depot (Fig. 1). Immunofluorescence analysis, magnetic resonance imaging (MRI) and BBB open-filed locomotor scores suggested that DOC-H was more competent for spinal cord repair by reducing hypertrophic scarring and promoting axon growth than the free docetaxel or the blank hydrogel composite. Furthermore, there was a substantial increase in the weight of rats treated with DOC-H, and no sign of pathological change was observed. Overall, the in situ gelforming hydrogel composite may serve as a promising system for microtubule-targeting agents in the treatment of SCI.

} Fig. 1. Illustration of PP-Si-PAMAM-Lac for recognition events and PDT inside hepatoma cell.

Keywords: glycoconjugated porphyrin, temperature-sensitive, specific targeting, PDT

Fig. 1. Schematic representation of DOC-H for sustained drug delivery at the spinal cord injury site.

References [1] Y.M. Chabre, R. Roy, Multivalent glycoconjugate syntheses and applications using aromatic scaffolds, Chem. Soc. Rev. 42 (2013) 4657- 4708.

Keywords: spinal cord injury, axonal regeneration, docetaxel, drug delivery

Abstracts / Journal of Controlled Release 259 (2017) e5–e195

Acknowledgements This work was financially supported by National S&T Major Project (2011ZX09102-001-10 and 2015ZX09301304-007). References [1] J. Rusche, F. Hellal, K.C. Flynn, S. Dupraz, D.A. Elliott, A. Tedeschi, M. Bates, C. Sliwinski, G. Brook, K. Dobrindt, M. Peitz, O. Brüstle, M.D. Norenberg, A. Blesch, N. Weidner, M.B. Bunge, J.L. Bixby, F. Bradke, Systemic administration of epothilone B promotes axon regeneration after spinal cord injury, Science 348 (2014) 347-352. [2] M.M. Pakulska, K. Vulic, R.Y. Tam, M.S. Shoichet, Hybrid crosslinked methylcellulose hydrogel: a predictable and tunable platform for local drug delivery, Adv. Mater. 27 (2015) 5002-5008.

doi:10.1016/j.jconrel.2017.03.299

Electrospun hydrogel fibrous scaffolds for rapid vascularized skin flap regeneration Xiaoming Suna,b, Ruoyu Chenga, Liying Chengb, Yuguang Zhangb,⁎, Wenguo Cuia,⁎ a Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, Suzhou 215007, China b Department of Plastic and Reconstructive Surgery, Ninth People's Hospital, Medical School of Shanghai Jiao Tong University, Shanghai 200011, China ⁎Corresponding authors. E-mail addresses: [email protected] (Y. Zhang), [email protected] (W. Cui) Random skin flaps transplantation is frequently used in plastic surgery. Due to limited length-to-width ratio, distal necrosis is always clinical problems. Thus, efforts to stimulate vascularization from the wound bed and promote blood supply for improving flap survival are still standing. The development of three-dimensional functional vascular networks is fundamental for a local random skin flap survival. Recent advances in tissue engineering, various kinds of biomaterial scaffolds have been implanted into animal body for improving vascularization [1]. Moreover, many studies reported that electrospun fibrous meshes were fabricated using synthetic or natural materials for vascularization. Previously, we found that eletrospun fibrous membranes made of natural materials are more beneficial for random skin flap survival compared with the synthetic ones [2]. Herein, we demonstrated an effective technique to synthesize a photocrosslinkable gelatin (GelMA) prepolymer by incorporating reactive methacrylamide groups to gelatin, and then electrospinning the resulting polymer forming photopolymerizable GelMA hydrogelbased fibers for accelerating vascularization. We found that the physical properties of the ultraviolet photo-crosslinkable GelMA hydrogel fibers, including water retention, stiffness, elasticity, mechanical strength and degradation, can be tailored by changing light exposure time (Fig. 1A). Furthermore, we observed that the optimized hydrogel scaffolds could

Fig. 1. (A) The morphology of electrospun fibers of GelMA. (B) Endothelial cells filaments are stained by phalloidin (green) and nuclei stained by DAPI (blue), and white points indicate the tubes. (C) Immunofluorescence staining of CD31 (red) of skin flap on 7 days after GelMA electrospun fibrous membrane implantation.

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support endothelial cells and dermal fibroblasts adhesion, proliferation and migration into the scaffolds, which facilitated vascularization. Importantly, a rapid formation of tubes could be observed after 3 days endothelial cells seeding in vitro (Fig. 1B). After GelMA fibrous scaffold implantation, the flap survival rate was significantly improved. Furthermore, there was more microvascular formation, which was potentially beneficial for the flap tissue vascularization (Fig. 1C). These data suggested that GelMA hydrogels can be used for biomedical applications that require the formation of microvascular networks, including the development of complex engineered tissues. Keywords: gelatin methacryloyl, photocrosslinkable hydrogel, vascularization, random skin flap Acknowledgements This work is supported by the NSFC (51373112, 21204056 and 81372073). References [1] J. Pu, F. Yuan, S. Li, K. Komvopoulos, Electrospun bilayer fibrous scaffolds for enhanced cell infiltration and vascularization in vivo, Acta Biomater. 13 (2015) 131-141. [2] X.M. Sun, R. Zheng, L.Y. Chen, X. Zhao, R. Jin, L. Zhang, Y. Zhang, Y.G. Zhang, W.G. Cui, Two-dimensional electrospun nanofibrous membranes for promoting random skin flap survival, RSC Adv. 6 (2016) 9360-9369.

doi:10.1016/j.jconrel.2017.03.300

Scientific fusion of liver-based therapy of traditional Chinese medicine theory and modern deoxyschizandrin nano-delivery system on the hepatoprotective activity Xiaona Liua,b, Shifeng Wanga, Zhisheng Wua,⁎, Zhaoyi Wanga, Yanjiang Qiaoa a Beijing University of Chinese Medicine, Beijing 101022, China b Binzhou Medical University, Yantai 256603, China ⁎Corresponding author. E-mail addresses: [email protected] (Z. Wu), [email protected] (Y. Qiao) Traditional Chinese medicine (TCM), an ancient and mysterious medical practice system, has gradually become the hot topic of disease prevention and therapy both in China and worldwide. Liver-based therapy of TCM theory is a key concept, which was presented by Professor Qi Wang, a National Chinese Medical Science Master. To reconcile TCM, traditionally valued empiricism and holistic philosophy, with the western approach to liver disease, such as a reproducible standardization, liposome-based nano-delivery system was used. Deoxyschizandrin (DS) is the major bioactive Schisandra lignin and exhibits hepatoprotective effect [1,2]. This work aimed to present the liver protection effect of DS loaded liposome (DS-liposome) based on the liver-based therapy of TCM theory (Fig. 1). Firstly, scanning electron microscope (SEM) and laser light scattering (LLS) were performed to analyze the morphology of liposomes. Furthermore, the antioxidant activity and the suppressing accumulation of cytoplasmic lipid droplet effect were studied. Morphology observations showed that liposomes were spherical with uniform size of less than 100 nm. The in vivo and in vitro fluorescence imaging study exhibited hepatic targeting effect of liposomes. L02 cells pretreated with DS-liposome showed an increased resistance to oxidative stress. Meanwhile, the robust phenotype-based HCS imaging microassay was developed to study the inhibiting adipogenesis of DSliposome in 3T3-L1 adipocytes. Moreover, DS-liposome exhibited definite hepatoprotective activity to reduce the H2O2 induced damage and the inhibiting accumulation of cytoplasmic lipid droplet. The results