Bong Sup Kim

Sustained delivery of doxorubicin using biodegradable pH/temperature-sensitive poly(ethylene glycol)-poly(β-amino ester urethane) multiblock copolymer hydrogels

Polymers containing amino urethane groups have great potential as polymeric hydrogel carriers for the delivery of drugs/proteins because of their non-toxicity and ability to form hydrogen bonds and ionic interactions with biomolecules. However, the reported gels have high molecular weights and/or are non-biodegradable or showed fast degradation. This study examined a series of low molecular weight, biodegradable pH/temperature-sensitive multiblock copolymer hydrogels composed of poly(ethylene glycol) (PEG) and poly(β-amino ester urethane) (PAEU) and their potential appication for drug sustained release. The copolymers were synthesized and characterized by 1H and 13C NMR, Fourier transform infrared spectroscopy and gel permeation chromatography. Aqueous solutions of the copolymer showed a gel-to-sol phase transition as a function of temperature in the pH range of 6.8–7.6. The gel window covered the physiological conditions (37 °C, pH 7.4). The gel region could be controlled by changing PEG/PAEU ratio, copolymer solution concentration and PEG molecular weight. A gel formed rapidly in situ after injecting the copolymer solution subcutaneously into SD rats. The non-cytotoxicity of this hydrogel was confirmed by in vitro cytotoxicity test and the in vitro release of doxorubicin from this hydrogel was sustained for more than 5 weeks. This novel injectable biodegradable pH/temperature-sensitive hydrogels can be a potential candidate for drugs carrier.

Effect of cyanate ester on the cure behavior and thermal stability of epoxy resin

Epoxy resin (diglycidyl ether of bisphenol A, DGEBA)/cyanate ester mixtures were cured with a curing agent, 4,4′-diaminodiphenylsulfone, and the effect of cyanate ester resin on the cure behavior and thermal stability in the epoxy resin was investigated with a Fourier transform infrared spectrometer, a rheometer, a dynamic mechanical analyzer, and a thermogravimetric analyzer. Cure reactions in the epoxy/cyanate ester mixture were faster than that of the neat epoxy system. The cure reaction was accelerated by increasing the cyanate ester resin component. Glass transition temperature and thermal stability in the cured resins were increased with increasing cyanate ester resin component. This may be caused by the increase of crosslinking density due to the polycyclotrimerization of the cyanate ester monomer to form triazine rings and the reaction of cyanate ester resin with the epoxy network.

Controlled release of human growth hormone from a biodegradable pH/ temperature-sensitive hydrogel system

Biodegradable pH/temperature-sensitive triblock copolymer hydrogels composed of poly(ethylene glycol) (PEG) and poly(β-amino ester urethane) (PAEU) were synthesized and characterized. The presence of urethane and tertiary amine groups in the synthesized copolymers could enhance the hydrogen bonds and ionic interactions between copolymers and drug/protein molecules, particularly the anionic-type. The existence of a copolymer solution at low pH and low temperatures (e.g. 20 °C, pH 6.0) facilitates the formulation of a hydrogel precursor with therapeutic agents, while the transition to the gel state at the physiological conditions (37 °C, pH 7.4) provides the potential application as a drug/protein carrier. The non-cytotoxicity of this hydrogel system was confirmed by the in vitro cytotoxicity test. The release of human growth hormone (hGH) from this hydrogel system was controlled for more than 5 days in vitro and 3 days in vivo without an initial burst, exhibiting the potential application as a protein carrier.

Preparation and Characterization of Polyimide/Carbon-Nanotube Composites

Polyimide/carbon nanotube (CNT) composite films, for potential use in high performance microelectronics and aerospace applications, were prepared by mixing a polyisoimide (PII) solution and a CNT suspension in NMP, followed by casting, evaporation and thermal imidization. The CNTs were modified by a nitric acid treatment to improve the thermal and electrical properties, as well as to provide good dispersion of the CNTs in a polymer matrix. The formation of functional groups on the modified CNT was confirmed by Raman spectroscopy. Scanning electron microscopy revealed the modified CNTs to be well dispersed in the polyimide matrix, with a uniform diameter of ca. 50 nm. The thermal stability of the films containing the CNTs was improved due to the enhanced interfacial interaction and good dispersion between the polyimide matrix and modified CNTs. In addition, the thermal expansion coefficient of the composites films was slightly decreased, but the dielectric constants increased linearly with increasing CNT content.

pH-Sensitivity Control of PEG-Poly(β-amino ester) Block Copolymer Micelle

Poly(ethylene glycol) methyl ether (PEG)-poly(β-amino ester) (PAE) block copolymers were synthesized using a Michael-type step polymerization, and the construction of pH-sensitive polymeric micelles (PM) investigated. The β-amino ester block of the block copolymers functioned as a pH-sensitive moiety as well as a hydrophobic block in relation to the ionization of PAE, while PEG acted as a hydrophilic block, regardless of ionization. The synthesized polymers were characterized using1H-NMR, with their molecular weights measured using gel permeation chromatography. ThepKb values of the pH-sensitive polymers were measured using a titration method. The pH-sensitivity and critical micelle concentration (CMC) of the block copolymers in PBS solution were estimated using fluorescence spectroscopy. The pH dependent micellization behaviors with various bisacrylate esters varied within a narrow pH range. The critical micelle concentration at pH 7.4 decreased from 0.032 to 0.004 mg/mL on increasing the number of methyl group in the bisacrylate from 4 to 10. Also, the particle size of the block copolymer micelles was determined using dynamic light scattering (DLS). The DLS results revealed the micelles had an average size below 100 nm. These pH-sensitive polymeric micelles may be good carriers for the delivery of an anticancer drug.

Structure development via reaction‐induced phase separation in tetrafunctional epoxy/polysulfone blends

For the cure process of tetrafunctional epoxy resin/polysulfone(EP/PSF) blends, we investigated the effect of cure temperature and blend composition on the phase separation behavior by light scattering and the structure development during cure by an optical microscope. The EP/PSF blend without the curing agent was shown to exhibit an LCST-type phase behavior (LCST = 241°C ). At the early stage of curing, the EP/PSF blend was homogeneous at the cure temperature. As the cure reaction proceeded, the blend was thrust into a two-phase regime by the LCST depression caused by the increase in a molecular weight of the epoxy-rich phase, and the phase separation took place via a spinodal decomposition ( SD ) or nucleation and growth (NG) mode, depending on the blend composition and the cure temperature. When cured isothermally at 220°C, the blend exhibited a sea-island morphology formed via the NG mode below 5 wt % PSF content, while the SD mode prevailed above 20 wt % PSF content. At the intermediate composition range, combined morphology with both sea-island and cocontinuous structure was observed. On the other hand, by lowering the cure temperature and/or increasing the content of PSF component, a two-phase structure with a shorter periodic distance was obtained. It seems that the rate of the phase separation is considerable reduced, while that of the cure reaction is not as much.

Novel pH and temperature-sensitive block copolymers: Poly(ethylene glycol)-b-poly(ε-caprolactone)-b-poly(β-amino ester)

ConclusionsBlock copolymers, composed of MPEG, PCLA and PAE, were synthesized through a combination of ring opening reaction and Michael reaction. Their aqueous solutions show a sensitive sol-gel transition by pH and temperature within a small pH range. The sol-gel phase diagrams of the block copolymer solutions were controlled deliberately by altering either the ratio of hydrophobic to hydrophilic blocks within the block copolymer or the PEG length. The aqueous block copolymer solution composed of MPEG=5,000, PEG/PCL ratio=1/0.3 and PAE=847 had a gel region including thein vivo conditions (37°C, pH 7.4). This polymer solution could be formulated with various drugs at pH 5∼6 buffer solution for the injection to the human body. This could be one of the candidate of the injectable hydrogel for the sustained release of drug.

Synthesis and characterization of MPEG-b-PDPA amphiphilic block copolymer via atom transfer radical polymerization and its pH-dependent micellar behavior

Block copolymer micelles are generally formed via the self-assembly of amphiphilic block copolymers in an aqueous medium. The hydrophilic and hydrophobic blocks form shell and core micelles, respectively. The block copolymers of methoxy poly(ethylene glycol) (MPEG)-b-poly(2-diisopropylamino)ethyl methacrylate (PDPA) were synthesized via atom transfer radical polymerization, with the macroinitiator synthesized by the coupling of 2-bromoisobutyryl bromide with MPEG in the presence of a triethyl amine base catalyst. The atom transfer radical polymerization of 2-diisopropylamino)ethyl methacrylate was performed in conjunction with anN,N,N′,N′’,N′’-pentamethyl-diethylenetriamine/copper bromide catalyst system, in DMF, at 70°C. The pH induced micellization/demicellization was studied using fluorescence, with a pyrene probe. Furthermore, the pH dependent micellization was confirmed using the microviscosity method, with a dipyme fluorescence probe. The pH dependant micelle size distribution was studied using dynamic light scattering. The characterization of the synthesized polymers was established using gel permeation chromatography and from the1H-nuclear magnetic resonance spectroscopy.

Pancreatic cancer therapy using an injectable nanobiohybrid hydrogel

Nanobiohybrid hydrogels, which are composed of inorganic nanoparticles and biodegradable polymeric hydrogels, have received special attention in the field of drug and protein delivery. These systems exploit the unique advantages of each component to improve the efficacy of the therapeutic agents and minimize undesirable side effects. The objective of this study was to develop a gemcitabine-loaded nanobiohybrid hydrogel to overcome the limitations of this anticancer drug, such as the very short half-life of gemcitabine (GEM) in plasma, the systemic toxicity from high-dose therapy, and the need for repeated administration during treatment. The proposed injectable nanobiohybrid hydrogel for controlled release of GEM was prepared through intercalation and adsorption of GEM to interlayer galleries and surfaces of montmorillonite (MMT) nanoparticles (forming MMT–GEM complexes), followed by the dispersion of the MMT–GEM complexes into the injectable, biodegradable, temperature-sensitive poly(e-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(e-caprolactone-co-lactide) hydrogel. The MMT–GEM complex and the nanobiohybrid hydrogel were characterized by X-ray diffraction analysis, particle size and zeta potential measurements, Fourier transform infrared spectroscopy, and scanning electron microscopy. Improvements in the properties of nanobiohybrid hydrogel in comparison with the pristine hydrogel were confirmed through sol–gel phase transition diagram, rheological measurement, and in vivo stability. The non-cytotoxicity of the nanobiohybrid hydrogel was proven by MTT assay using the 293T cell line. Compared with the pristine hydrogel, the in vitro GEM release from the nanobiohybrid hydrogel showed a considerably prolonged GEM release time and a much lower initial burst. The antitumor efficacy studies on pancreatic tumor-bearing mice revealed a significant inhibition of tumor growth. Hence, these findings demonstrate that the nanobiohybrid hydrogel is a desirable carrier for controlled release of GEM in the treatment of pancreatic cancer.

Evaluation of AgHAP-containing polyurethane foam dressing for wound healing: synthesis, characterization, in vitro and in vivo studies

Silver-containing dressings have been widely used to control wound infection. In this study, we developed various amounts of silver-hydroxyapatite (AgHAP)-containing polyurethane foams (PUFs) (AgHAP-PUFs), and their biological properties including biocompatibility, antibacterial activities, and in vivo wound healing properties were evaluated in the Sprague-Dawley rat model. From electron microscopy imaging, it was found that AgHAP particles are uniformly dispersed inside PUFs. The release of Ag from PUFs was dependent on both time and concentration, i.e., the amount of released Ag was significantly higher with increasing immersion time and Ag content in the PUFs. From the cytotoxicity test, AgHAP-PUFs exhibited high antibacterial efficacy against four pathogenic bacteria, and they were not cytotoxic against L-929 fibroblast cells. AgHAP-PUF treated groups exhibited scar-free wound healing by promoting re-epithelialization and collagen deposition in the infected excision wound model. Overall, it is evident that AgHAP-PUFs may be considered as a good antibacterial wound dressing for infected wounds due to their good antibacterial activity, biocompatibility, and wound healing rate.