Journal of Bioactive and Compatible Polymers current issue

A Polyurethane-Gelatin Hybrid Construct for Manufacturing Implantable Bioartificial Livers

Wei Xu, , Xiaohong Wang, , Yongnian Yan, , Renji Zhang, — 2008-09-04

A novel 3D hybrid construct was developed for liver manufacturing by depositing biodegradable polyurethane (PU) and a naturally derived polymer gelatin simultaneously via a double nozzle rapid prototyping (RP) technique. A grid object was produced by precisely and simultaneously dispersing the PU and gelatin to form 3D constructs with interconnected macro-channels at a low temperature (-28°C). Micro-pores were formed by freeze-drying the constructs. The PU polymer provided mechanical support while gelatin provided accommodation for implant cells. The hydrophilicity of the hybrid constructs was between the pure PU and pure gelatin structures. The interconnected channels allow nutrients and oxygen to be supplied throughout the construct as well as provide space for the attachment of cells. The design and fabrication strategies, used to create complex physical objects directly from computer aided design (CAD) models, represent a promising technique for implantable bioartificial livers. It is anticipated that these PU-gelatin hybrid constructs will serve as a useful model for bioartificial liver manufacturing.

New Multicomponent Bioerodible Electrospun Nanofibers for Dual-controlled Drug Release

Piras, A.M., Chiellini, F., Chiellini, E., Nikkola, L., Ashammakhi, N. — 2008-09-04

The objective of this study was to evaluate the bioerodible polymer poly(maleic anhydride-alt-2-methoxyethyl vinyl ether) n-butyl hemiester, for multicomponent drug-loaded nanofibers produced by electrospinning. Diclofenac sodium (DS) and human serum albumin (HSA) were used as conventional drug and biopharmaceutical models. The influence of drug loading was correlated to beads presence, morphology and fibers diameter. When DS and HSA were loaded separately, a uniform distribution within fibers and beads was observed. However, when both components were loaded simultaneously, a heterogeneous distribution of DS was observed with a prominent amount in the cylindrical beads. The in vitro drug release evaluation from these nanomaterials displayed an independent delivery of the two components. These studies support the feasibility of multicomponent, bioerodible polymeric nanofibers preparation loaded with combination of traditional drugs and proteins.

An In Situ Gel-Forming Heparin-Conjugated PLGA-PEG-PLGA Copolymer

Lih, E., Yoon Ki Joung, , Jin Woo Bae, , Ki Dong Park, — 2008-09-04

Novel heparin-conjugated PLGA-PEG-PLGA hydrogels were prepared via Michael-type addition between thiolated heparin and PLGA-PEG-PLGA diacrylate. The thiolated heparin (HP-SH) was conjugated with thiolacid dihydrazide followed by reduction. The structure and the thiol determination of obtained HP-SH were characterized by ¹H NMR and the Ellman method. Anticoagulant activity and pK_a of the HP-SH were determined by aPTT test and UV absorbance measurement which were 79.3% and 10.5, respectively. The PLGA-PEG-PLGA diacrylate was synthesized by bulk ring-opening polymerization of D,L-lactide (DLLA) and glycolide (GA) with PEG and stannous 2-ethylhexanoate, followed by the acrylation of the terminal groups. HP—SH was then conjugated to PLGA-PEG-PLGA diacrylate by Michael addition. Phase diagrams of the hydrogels were obtained by vial tilting; the release of heparin from the hydrogels exhibited temperature dependent sol—gel transition behavior. These in situ-forming heparin-conjugated hydrogels are novel as injectable and tissue-compatible scaffold formation, thermo-sensitivity, and growth factor binding.

Effects of Fungal-derived High Molecular Weight Chitosan on 5-Fluorouracil-induced Adverse Reactions

2008-09-04

The effects of fungal-derived high molecular weight chitosan (HMWC) on the prevention of 5-fluorouracil (5-FU)-induced side-effects were studied in a sarcoma-bearing mice model. 5-FU (12.5mg/kg) was gargled into the mice with or without HMWC (25, 75, and 150mg/kg) every 12 h for consecutive 8 or 16 days in different experiments. The HMWC (25—150 mg/kg) exerted no toxicity and did not interfere with the anti-tumor activity of 5-FU on sarcoma-bearing mice. HMWC in a higher dose (150 mg/kg) partially protected 5-FU-induced cytotoxicity on peripheral leukocytes, lymphocytes, and bone marrow CD-19 positive cells. HMWC reversed the 5-FU suppression of intestine sucrase activity and attenuated the 5-FU-induced diarrhea. Bone marrow cells micronucleus and DNA comet assays demonstrated that HMWC significantly reversed 5-FU-induced genome toxicity to marrow cells. These results suggested that fungal-derived HMWC attenuated the 5-FU-induced bone marrow and gastrointestinal toxicity, and has the potential for clinical applications in the future.

Syntheses and Evaluations of Antitumor and Antiangiogenic Compounds Conjugated with 5-Fluorouracil and Ascorbic Acid

Lee, S.-M., Kim, B.-G., Ha, C.-S., Chung, I., Dong Xie, — 2008-09-04

The new multifunctional antitumor conjugates containing ascorbic acid and 5-fluorouracil (5-FU) were synthesized from bicyclo[2.2.2]oct-7-ene-2,3,5,6-tetracarboxylic dianhydride, ascorbic acid and/or a chain spacer, followed by condensation with 5-FU. The synthesized conjugates were identified by ¹H and ¹³C NMR spectroscopies and elemental analysis. The in vitro cytotoxicities of these conjugates were determined and their antitumor activity was evaluated. The IC₅₀ values (drug concentration for 50% inhibition of tumor growth) indicated that the synthesized conjugates were better inhibitors against cancer cells and were lower in cytotoxicity than the free 5-FU. The in vivo antitumor activity of the conjugates was examined against mice bearing the sarcoma 180 tumor cells. The life spans (T/C) of mice treated with the conjugates were higher than for the free 5-FU. In addition, the synthesized conjugates showed excellent antiangiogenic activity, based on the embryo chorioallantoic membrane assay.

Microwave-assisted Preparation of Magnetic Albumin Microspheres

Chen, C.-Y., Qi Long, , Li, X.-H., Jiao Xu, — 2008-09-04

A new microwave-assisted method was used to prepare magnetic Fe₃ O₄ particles and magnetic bovine albumin microspheres. The microwave method produced smaller particles and is faster than traditional methods. The optimum conditions to prepare the Fe₃O₄ particles were three minutes at pH 13 and 80°C. Magnetic microspheres containing albumin were synthesized based on heating times and temperatures to form microspheres with different properties. For example, heating for 4min, at 160°C, yielded smaller sized microspheres (30 µm). Confirmed by XRD, SEM, and FT-IR that iron oxide particles were encapsulated in biocompatible proteins, The thermal stability of the microspheres were determined by DSC and TG. The magnetic properties were determined by UV—VIS spectraphotometry and a Guoy magnetic balance. This microwave process could become a preferred method for the synthesis of magnetized protein microspheres.