Formulation and Evaluation of Chitosan‐Gellan Based Methotrexate Implants

An implant controlled‐release system for methotrexate delivery based on a polyion complex composed of chitosan and gellan was investigated. Multi‐layered implant was prepared by using poly(vinyl alcohol), gellan and chitosan. Two chitosan layers sandwiched the poly(vinyl alcohol)‐gellan layer, which acted as a methotrexate reservoir. The prepared implant was evaluated for swellability, in vitro and in vivo release and biodegradation studies. The equilibrium swelling and methotrexate release was found to depend on a concentration of calcium chloride, which was used as a crosslinking agent for gellan. Drug‐loaded implants were subcutaneously implanted in the back of Wistar rats. The in vivo studies showed that methotrexate was released slowly for a period over 30 days and also there was no fibrous capsule formation around the implant indicating the biocompatibility of the implant.     

FT‐IR characterization and hydrolysis of PLA‐PEG‐PLA based copolyester hydrogels with short PLA segments and a cytocompatibility study

A series of the biodegradable copolyester hydrogels was prepared using a redox‐initiated polymerization with a constant 1:9 mole ratio of the Boltorn‐based acrylate and diacrylate triblock comacromonomers. The Boltorn® macromonomer was derived from the hyperbranched polyester Boltorn H20, which was functionalized at each terminus with poly(ethylene glycol) acrylate, and the diacrylate triblock macromonomer was poly (lactide‐b‐ethylene glycol‐b‐lactide) diacrylate. The hydrolysis of the copolyesters at pH 7.4 in a phosphate buffered saline solution at 37 °C was studied using ATR‐FTIR spectroscopy. It was found that the presence of the Boltorn, the PEG, and lactide block lengths both play vital roles in determining the structure‐property relationships in these materials. The ATR‐FTIR studies showed that with increasing lactide segment length, the rate of ester hydrolysis increased due to the increased concentration of the hydrolytically sensitive poly(lactic acid) (PLA) ester groups in the network. However, incorporation of Boltorn into the PLA‐PEG‐PLA copolymer did not significantly change the kinetic rate constant for hydrolysis of the PLA segments. The cytocompatibility of a typical one of these materials in the presence of its degradation by‐products was assessed using cultured osteoblasts from the rat. The hydrogel was degraded for 28 days and found to be cytocompatible with osteoblasts over days 23 to 28 of the hydrolysis period. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 5163–5176     

Amphiphilic depsipeptide‐based block copolymers as nanocarriers for controlled release of ibuprofen with doxorubicin

Well‐defined amphiphilic multiblock copolymers PDMAEMA‐b‐P(IBMD‐co‐PDO)‐b‐PEG‐b‐P(IBMD‐co‐PDO)‐b‐PDMAEMA [PDMAEMA‐PIBMD‐PPDO‐PEG], based on poly(2‐(dimethylamino)ethyl methacrylate) block (PDMAEMA), poly(3(S)‐isobutyl‐morpholine‐2,5‐dione‐co‐p‐dioxanone) block (P(IBMD‐co‐PDO)), and poly(ethylene glycol) block (PEG) were successfully synthesized by combination of ring‐opening polymerization (using 3(S)‐isobutyl‐morpholine‐2,5‐dione and p‐dioxanone initiated by hydroxyl end of PEG) and atom transfer radical polymerization (ATRP). Furthermore, all these copolymers were characterized by ¹H NMR, ¹³C NMR, Fourier transformed‐infrared, gel permeation chromatography, differential scanning calorimetry, and thermogravimetric analysis measurements. The degradation experiments showed that the molecular weight of PDMAEMA‐PIBMD‐PPDO‐PEG decreased along with degradation time. In addition, these copolymers could readily self‐assemble into nanosized microspheres in phosphate buffered solution. Ibuprofen (IBU) and doxorubicin (DOX) as a kind of combined model drugs were loaded into these microspheres by the combination of ionic interaction and hydrophobic effect. These copolymer microspheres exhibited high loading capacity (LC, up to 26.88%), encapsulation efficiency (EE, up to 61.29%), and sustained release behavior of IBU–DOX in phosphate buffered solution. The results of transmission electron microscopy and dynamic light scattering showed that the microspheres were well‐defined uniform spherical particles with average diameter less than 120 nm. Therefore, it can be envisaged that these copolymer systems are promising candidates for controlled release application. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3213–3226     

Creation of biofunctionalized plasma polymerized allylamine gradients

A chemical gradient possessing gradual change of amine concentration for every 100 carbon atoms (NH_x/100 C) from 4.03 to 1.98 was prepared by plasma polymerization of allylamine on polypropylene films. Electron spectroscopy for chemical analysis and water contact angle (WCA) measurements revealed that the nitrogen incorporation resulted in the amine functionality (C? N binding) and, therefore, the formation of the wettability gradient. The gradient showed the WCAs varied from 15° to 90° as the change of amine concentration on the gradient from the nitrogen rich end to the nitrogen deprived end. Furthermore, the interactions between the gradient with mammalian cells revealed that more than twofold cell density was found at the nitrogen rich end when compared with the nitrogen deprived end. Plasma polymerization was demonstrated as an effective method to create controllable chemical gradient and the obtained allylamine gradient was useful for biomaterial applications. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2013 , 51, 1361–1367     

Synthesis,physicochemical characteristics,and biocompatibility of self‐assemble polymers bearing guanine,cytosine, uracil,and thymine moieties

We synthesized chemically well‐defined brush (i.e., comb‐like) polymers bearing guanine, cytosine, uracil, or thymine moieties at the bristle ends. The polymers were stable up to 220 °C and were readily solution‐processable, yielding high‐quality films. Interestingly, the brush polymers favorably self‐assembled to form molecular multibilayer structures stabilized by hydrogen bonding interactions among the nucleobase moieties at the bristle ends, which provided nucleobase‐rich surfaces. The multibilayer‐structured polymer films showed high water affinity. They also displayed selective protein adsorption, suppressed bacterial adherence, facilitated cell adhesion, and exhibited good biocompatibility in mice. The brush polymer DNA‐mimicking comb‐like polymers are suitable as biomaterials and in protein separation applications. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 1151–1160     

Bioreducible hyperbranched polyglycerols with disulfide linkages: Synthesis and biocompatibility evaluation

In this article, we describe the development of multifunctional, water‐soluble hyperbranched polyglycerols containing redox‐sensitive disulfide linkages as a new class of biodegradable polymers. The polymers were synthesized by the anionic ring opening multibranching (co)polymerization of glycidol with an epoxide monomer bearing disulfide groups, 2‐((2‐oxiran‐2‐ylmethoxy)ethyl)disulfanyl) ethan‐1‐ol. Polymerizations were optimized at 65 °C unlike the homopolymerization of glycidol. Both low (5–10 kDa) and high (100 kDa) molecular weight polymers were synthesized in a controlled manner with low polydispersity. The polymers underwent degradation in presence of reducing agents such as tris(2‐carboxyethyl)phosphine, dithiothreitol, and glutathione resulting in low molecular weight fragments with thiol groups. Blood compatibility analysis using coagulation, platelet activation, complement activation and red blood cell lysis assays as well as cell toxicity analysis using MTS assay revealed the excellent biocompatibility of these newly synthesized polymer architectures. All these features make these polymers suitable for intracellular delivery of therapeutic molecules. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2104–2115     

Effect of the graft ratio on the properties of polythiophene‐g‐poly(ethylene glycol)

Graft copolymers formed by anchoring poly(ethylene glycol) (PEG) chains to conjugated polythiophene have been prepared by copolymerizing two compounds: unsubstituted α‐terthiophene (Th₃) and a thiophene‐derived macromonomer having an α‐terthiophene conjugated sequence and one Th₃ bearing a PEG chain with molecular weight of 2000 as substitute at the 3‐position of the central heterocycle (Th₃‐PEG₂₀₀₀). The grafting ratio of the resulting copolymers (PTh₃^*‐g‐PEG), which were obtained using 75:25 and 50:50 Th₃‐PEG₂₀₀₀:Th₃ weight ratios, is significantly smaller than that of copolymers derived from polymerization of macromonomers consisting of a α‐pentathiophene sequence in which the central ring bears a PEG chain of M_w = 2000 (PTh₅‐g‐PEG). The electroactivity and electrochemical stability of PTh₃^*‐g‐PEG is not only higher than that of PTh₅‐g‐PEG but also higher than that of PTh₃, the latter presenting a very compact structure that makes difficult the access and escape of dopant ions into the polymeric matrix during the redox processes. Furthermore, the optical π‐π^* lowest transition energy of PTh₃^*‐g‐PEG is lower than that of both PTh₅‐g‐PEG and PTh₃. These properties, combined with suitable wettability and roughness, result in an excellent behavior as bioactive platform of PTh₃^*‐g‐PEG copolymers, which are more biocompatible, in terms of cellular adhesion and proliferation, and electro‐compatible than PTh₅‐g‐PEG. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015 , 53, 239–252     

Polyisobutylene‐based biomaterials

This article highlights the biomaterial‐related research of the Macromolecular Engineering Research Centre (MERC). The MERC group concentrated on polyisobutylene (PIB)‐based biomaterials. In this article, first the unique properties of PIB are discussed, followed by a review of PIB‐based potential biomaterials. MERC's systematic research program aimed to develop novel PIB‐based biomaterials is then highlighted, including surface modification and biocompatibility studies. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 3091–3109, 2004     

Conductivity,impurity profile,and cytotoxicity of solvent‐extracted polyaniline

Understanding the correlation between the preparation, purification, impurity leaching, and cytotoxicity of polyaniline is crucial for the application of this conducting polymer in biomedicine. Polyaniline hydrochloride was purified in a Soxhlet extractor by using six different solvents: methanol, 1,2‐dichloroethane, acetone, ethyl acetate, hexane, or 0.2 M aqueous hydrochloric acid. The chromatographic analyses of impurities leached out of the polymer into the solvents confirmed differences in impurity profiles, which depended on the polarity of the extraction solvent. Compared with the original polymer, the conductivity of purified polyanilines increased in dependence on the amount and type of extracted impurities. The cytotoxicity of purified samples determined on the mouse embryonic fibroblast cell line NIH/3T3 using MTT assay improved as well. Methanol and 0.2 M hydrochloric acid were the most efficient solvents capable of extracting low‐molecular‐weight impurities, and thus reducing polyaniline cytotoxicity. The absence of cytotoxicity was observed at an extract concentration of 10%. Extraction with suitable solvents can, therefore, be a possible way of obtaining cyto‐compatible polyaniline with sufficient conductivity. Copyright © 2015 John Wiley & Sons, Ltd.