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Using nerve guide conduits (NGCs) to promote the regeneration of PNI is a feasible alternative to autograft. Compared with NGCs made of single material, composite NGCs have a greater development prospect. Our previous research has confirmed that poly(D, L-lactic acid)/β-tricalcium phosphate/hyaluronic acid/chitosan/nerve growth factor (PDLLA/β-TCP/HA/CHS/NGF) NGCs have excellent physical and chemical properties, which can slowly release NGF and support cell adhesion and proliferation. In this study, PDLLA/β-TCP/HA/CHS/NGF NGCs were prepared and used to bridge a 10 mm sciatic nerve defect in 200–250 g Sprague-Dawley (SD) rat to verify the performance of the NGCs in vivo. Substantial improvements in nerve regeneration were observed after using the PDLLA/β-TCP/HA/CHS/NGF NGCs based on gross post-operation observation, triceps wet weight analysis and nerve histological assessment. In vivo studies illustrate that the PDLLA/β-TCP/HA/CHS/NGF sustained-release NGCs can effectively promote peripheral nerve regeneration, and the effect is similar to that of autograft. [ABSTRACT FROM AUTHOR]

A novel conductive drug-loading system was prepared by using an improved emulsion electrostatic spinning method which contained polylactic acid (PLA), graphene oxide (GO), and nerve growth factor (NGF) coated with bovine serum albumin (BSA) nanoparticles. Firstly, the structure, mechanical properties, morphology and electrical conductivity of PLA/GO electro spun fiber membranes with different GO ratios were characterized. PLA/GO scaffolds can exhibit superior porosity, hydrophilic and biomechanical properties when the GO incorporation rate is 0.5%. The addition of GO in the PLA/GO electro spun fiber membranes can also create appropriate pH environment for the repair of injured nerve when the GO incorporation rate is above 0.5%. Secondly, PLA/GO/BSA/Genipin/NGF particles (with a ratio of BSA/NGF = 3:1) prepared by modified emulsion electro spinning method will release more NGF than PLA/GO/NGF particles. In addition, PLA/0.5%GO/NGF scaffold can maintain its structure stability for at least 8 weeks observed by scanning electron microscope (SEM). Moreover, the degradation of PLA/0.5%GO/NGF scaffold is consistent with its weight loss. Finally, in vitro assay confirmes that PLA/GO composite scaffold exhibits low cytotoxicity to RSC96 cells. Cellular results have demonstrated that PLA/0.5%GO/NGF sustained-release drug sustained-release system with appropriate electrical stimulation (ES) can promote PC12 cell proliferation, and it can maintain its differentiation capability for at least 3 weeks. In conclusion, PLA/0.5%GO/NGF sustained-release drug sustained-release system can maintain its biological activity for at least 3 weeks and promote cell proliferation with appropriate ES. [ABSTRACT FROM AUTHOR]

Conductive polymers show great promise because of their electrical property based on bioelectricity in vivo. In order to search electro-activity materials which insure abduction of tissue, we synthesized conductive nerve conduits with poly-dl-lactic-acid (PDLLA) and tetra-aniline (TA). Preparation technology of TA was optimized, and the properties of the conduit were studied. RSC96 cell were used to investigate the toxicity and electrical stimulation effect. SD rats were used to assess biocompatibility in vivo. The results showed that the reaction ratio of 1:1, the reaction time of 2 h and the HCl concentration of 2 mol/L were the optimum conditions for synthesis of TA. The influence of TA content on the mechanical properties, hydrophilicity, conductivity and microstructure of the nerve conduit was evaluated. Cell and histocompatibility study showed PDLLA/TA possessed good biocompatibility. These results showed it had application values in tissue projects. [ABSTRACT FROM AUTHOR]

A multifunctional drug delivery system (GNRs@mSiO2-HA-RGD) was developed by conjugating targeting ligand hyaluronic acid (HA) and RGD with mesoporous silica- coated gold nanorods (GNRs@mSiO2) for dual-targeted chemo-photothermal therapy. The physiochemical properties of the prepared nanoparticles were characterized by FTIR, UV-vis spectra, and 1H NMR. Doxorubicin hydrochloride (DOX), an anticancer drug, was used as the model drug to investigate the drug loading, in vitro drug release profiles and cytotoxicity. The experimental results show that DOX-GNRs@mSiO2-HA-RGD is synthesized with a mean diameter of 116 nm and a sufficient load capacity of about 19.8%. It also has pH-enzyme sensitive and NIRtriggered drug release manner. Cellular uptake indicates that DOX-GNRs@mSiO2-HA-RGD exhibits a higher cellular uptake via CD44 receptor and integrin receptor mediated endocytosis compared with the GNRs@ mSiO2 modified with one receptor or no receptor. In comparison with chemotherapy or photothermal therapy alone, DOX-GNRs@mSiO2-HA-RGD displayes the synergistic effects and achieves a higher therapeutic efficacy. It can be expected that DOX-GNRs@mSiO2-HA-RGD is a potential dual-targeted chemo-photothermal therapeutic platform for effective cancer treatment. [ABSTRACT FROM AUTHOR]

This work aimed to develop an intelligent multi-target tracking hyaluronic acid-RGD-chlorambucil-quantum dots (HA-RGD-CLB-QDs) drug delivery system. After deacetylated, hyaluronic acid was reacted with anticancer drug chlorambucil, RGD, and quantum dots to obtain the HA-RGD-CLB-QDs drug delivery system. The characterization by FT-IR, H NMR, TEM, XPS, DLS, and UV-vis absorption and fluorescence spectra show that the system is successfully constructed with an average particle size of about 70 nm. The results of the drug release profile show that that the system has a pH and enzyme sensitive controlled release behaviour. Moreover, cellular uptake and toxicity results show that the system has an ideal dual receptor-mediated endocytosis pathway that significantly enhances the efficacy of CLB tumor therapy and has a lower toxicity to normal cells.The system shows the potential application as a carrier for cancer therapy. [ABSTRACT FROM AUTHOR]

The aim of this study was to obtain the fillers in the lumen of hollow nerve conduits (NCs) to improve the microenvironment of nerve regeneration. A pH-induced injectable chitosan (CS)-hyaluronic acid (HA) hydrogel for nerve growth factor (NGF) sustained release was developed. Its properties were characterized by gelation time, FT-IR, SEM, in vitro swelling and degradation. Furthermore, the in vitro NGF release profiles and cell biocompatibility were also investigated. The experimental results show that the CS-HA aqueous solution can undergo a rapid gelation 3 minutes after its environmental pH is changed to 7.4. The CS-HA hydrogel has interconnected channels with a controllable pore diameter and with a porosity of about 80%. It has a favorable swelling behavior and can be degraded by about 70% within 8 weeks in vitro and is suitable for NGF release. The CS-HA/NGF hydrogel exhibits a lower cytotoxicity and is in favor of the adhesion and proliferation of the BMMSCs cells. It is indicated that the CS-HA/NGF will be a promising candidate for neural tissue engineering. [ABSTRACT FROM AUTHOR]

A series of novel water soluble chitosan derivatives as gene vectors was synthesized. The delivery systems were tested for their ability to form complexes with plasmid DNA by utilizing agarose gel electrophoresis, particle size analysis, zeta potential measurement and scanning electron microscopy. Furthermore, cytotoxicity of chitosan derivatives and transfection efficiency of polyplexes were evaluated in vitro. The experimental results showed that the novel chitosan derivatives had lower cytotoxicity, good DNA condensation, and higher transfection efficiencies compared to chitosan in both 293T and HeLa cell lines. It was indicated that these chitosan derivatives were promising candidates for non-viral gene vectors [ABSTRACT FROM AUTHOR]

The use of methotrexate (MTX), an anticancer drug for the treatment of hematologic malignancies, has been limited in the clinical application due to its poor water solubility, high clearance rate, and lack of target specificity. To solve these problems, O, N-carboxymethyl chitosan-dipeptide-MTX conjugates have been synthesized and characterized by fourier transform infrared radiation spectroscopy and proton nuclear magnetic resonance (H NMR). All polymeric conjugates showed satisfactory water solubility. The results of the study revealed that drug release and toxicity were affected by employing polymeric conjugation strategy and dipeptide spacers [glycylglycine (Gly-Gly), glycyl- l-phenylalanine (Gly-Phe), glycyl- l-tyrosine (Gly-Tyr)]. It has been found that drugs could be effectively loaded and released when polymeric prodrugs were combined with a dipeptide spacer. In conclusion, O, N-CMCS-dipeptide-MTX polymeric prodrugs could potentially be used as responsive drug delivery systems. [ABSTRACT FROM AUTHOR]