Ji Heung Kim

Core-stabilized Polymeric Micelle as Potential Drug Carrier: Increased Solubilization of Taxol

ABSTRACTWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWW Poly(ethylene glycol-b-lactide) possessing a methoxygroup at the poly(ethylene glycol) (PEG) chain end anda polymerizable methacryloyl group at the poly(lacticacid) (PLA) chain end (MeO–PEG/PLA–methacryloyl)was prepared by an anionic ring-opening polymerizationof ethylene oxide and DL -lactide in tandem mannerinitiatedwithapotassium2-methoxyethanolate,followedby end-capping with an excess of methacrylic anhydride.The molecular weight of the obtained polymer wascontrolled by the initial monomer/initiator ratio, whichwas confirmed by the combination of gel permeationchromatography and nuclear magnetic resonance ana-lyses. The functionality of the methacryloyl–PLA endwas almost quantitative. The MeO–PEG/PLA–metha-cryloyl (38/35; these numbers in parentheses denote themolecular weights of PEG and PLA segments divided by100, respectively) formed a core–shell type sphericalmicelle in aqueous media obtained by a dialysistechnique, the cumulant diameter of which was ca.30nm with very low polydispersity factor.The methacryloyl group adjacent to the PLA waspolymerized in the PLA core of the micelle. Thepolymerizationproceededthermallywithradicalinitiatorand photochemically with photo-initiator to producecore-polymerized nanoparticles, which was found byspectroscopic and light-scattering techniques. Taxol-incorporated micelles were prepared to entrap Taxol intoMeO–PEG/PLA–methyacryloyl block copolymer mi-celles by the oil/water emulsion method. Copyright O1999 John Wiley & Sons, Ltd.KEYWORDS: polymeric micelle; stable nanoparticle;drugdeliverysystem;PEG/PLAblockcopolymer;micellestability; taxol

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.

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.

Biodegradable Thermo- and pH-Respon- sive Hydrogels Based on Amphiphilic Poly- aspartamide Derivatives Containing N,N-Diisopropylamine Pendants

Hydrogels are hydrophilic polymer networks that canabsorb large amounts of water, but are insoluble due to thepresence of physical or chemical crosslinks, entanglements,or crystalline regions. Hydrogels can have various biomedi-cal applications such as drug delivery systems, biosensors,contact lenses, catheters, and wound dressings.Recently, stimuli-responsive polymers and hydrogel mate-rials have attracted considerable attention in the field ofnovel drug delivery and tissue engineering due to theirpromising potential. Among them, polymer and hydrogelsystems that undergo a phase transition and volume-phasetransition in response to environmental stimuli, such as tem-perature and pH, have been widely investigated for use ingene or tumor targeting delivery, oral drug delivery, andother medical devices.

In vitro and in vivo Application of PLGA Nanofiber for Artificial Blood Vessel

Poly(lactic-co-glycolic acid) (PLGA) tubes (5 mm in diameter) were fabricated using an electro spinning method and used as a scaffold for artificial blood vessels through the hybridization of smooth muscle cells (SMCs) and endothelial cells (ECs) differentiated from canine bone marrow under previously reported conditions. The potential clinical applications of these artificial blood vessels were investigated using a canine model. From the results, the tubular-type PLGA scaffolds for artificial blood vessels showed good mechanical strength, and the duallayered blood vessels showed acceptable hybridization behavior with ECs and SMCs. The artificial blood vessels were implanted and substituted for an artery in an adult dog over a 3-week period. The hybridized blood vessels showed neointimal formation with good patency. However, the control vessel (unhybridized vessel) was occluded during the early stages of implantation. These results suggest a shortcut for the development of small diameter, tubular-type, nanofiber blood vessels using a biodegradable material (PLGA).

Cellular-uptake behavior of polymer nanoparticles into consideration of biosafety

Nanoparticles have tremendous potential in cancer prevention, detection and augmenting existing treatments. They can target tumors, carry imaging capability to document the presence of tumors, sense pathophysiological defects in tumor cells, deliver therapeutic genes or drugs based on the tumor characteristics, respond to external triggers to release an appropriate agent, document the tumor response, and identify the residual tumor cells. Nanoparticles < 30 nanometers in diameter show unexpected and unique properties. Furthermore, particles < 5 nanometers in size can easily penetrate cells as well as living tissues and organs. This study evaluated the safety of nano materials in a living body and the relationship between the living tissue and synthetic nano materials by examining thein-vitro cytotoxicity of poly(lactic-co-glycolic) acid (PLGA) nano-spheres and fluorescein isothiocynate(FITC)-labeled dendrimers as polymeric nanoparticles. PLGA was chosen because it has been used extensively for biodegradable nanoparticles on account of its outstanding bio-compatibility and its acceptance as an FDA approved material. The dendrimer was chosen because it can carry a molecule that recognizes cancer cells, a therapeutic agent that can kill those cells, and a molecule that recognizes the signals of cell death. Cytotoxicity in L929 mouse fibroblasts was monitored using MTT assay. Microscopic observations were also carried out to observe cell growth. All assays yielded meaningful results and the PLGA nanoparticles showed less cytotoxicity than the dendrimer. These nanoparticles ranged in size from 10 to 100 nm according to microscopy and spectroscopic methods.

Preparation and Properties of PEG-Modified PHEMA Hydrogel and the Morphological Effect

ConclusionsNovel HEMA based hydrogels modified by a PEG graft were prepared by the crosslinking polymerization of HEMA in the presence of a methacryloyl PEG macromer with different chain length. The increasing degree of swelling and the decreasing surface contact angle highlight the increasing hydrophilic nature of the gels modified by incorporating PEG. The PEG modified PHEMA gels had a porous network structure with pore sizes ranging from submicron to tens of microns, which changed according to composition. From the cytotoxicity test, the modified gel was found to be non-toxic and biocompatible. This material might applicable as a material for controlled drug delivery and as a gel scaffold in tissue engineering.

Preparation and chain-extension of P(LLA- b -TMC- b -LLA) triblock copolymers and their elastomeric properties

ABA triblock copolymers ofL-lactide and trimethylene carbonate with several different compositions were prepared by sequential ring-opening polymerization in the presence of diethylene glycol. Also chain-extension reactions of the resulting copolymers were carried out using hexamethylene diisocyanate to produce relatively high molecular weight polymers, which could be cast into elastomeric tough films. The polymers with certainL-lactide contents were partially crystalline, exhibiting two-phase morphology. The polymer films showed reversible elastic behavior under tensile tension, providing a novel thermoplastic elastomer possessing desirable properties such as biodegradability and good mechanical properties.

Controlled Release Behavior of Bioactive Molecules from Photo-Reactive Hyaluronic Acid-Alginate Scaffolds

There are three important components in tissue engineering: the cells, signaling factors (cytokines and growth factors), and scaffolds. To obtain finely engineered tissue, all three components should perform their individual functions and be fully integrated with each other. For the past few years, we have studied the characteristics of photodimerizable HA (CHA)/alginate (CA) composite materials. CHA/CA complex hydrogels, which were irradiated under UV light and then treated with calcium ions, were found to have good biocompatibility, mechanical properties and water resistance for implantable tissue scaffolds. In this study, we introduced a cell growth factor (basic fibroblast growth factor; bFGF) into the CHA/CA scaffolds and studied its release behavior. We also introduced tetracycline hydrochloride and flurbiprofen into the same scaffolds as model activation factors and evaluated their release behaviors from the scaffolds. The drug release rate from the materials was influenced by various parameters, such as the degree of crosslinking, the crosslinker type, the physico-chemical properties of the drug, and the amount of the drug in the polymer. The results indicated that the negatively charged CHA/CA composite materials showed sustained release behavior and that HA has a particularly strong negative charge, making it attractive toward tetracycline hydrochloride and bFGF, but repulsive toward flurbiprofen.

Preparation and Properties of Alginate/Polyaspartate Composite Hydrogels

This study examined the swelling behavior andin vitro release of a model drug, tetracycline-HCl, from alginate and alginate-polyaspartate (Alg-PASP) composite gel beads. The alginate and Alg-PASP composite beads were prepared using an ionic crosslinking method with aqueous Ca2+. Their microporous morphology was observed by scanning electron microscopy. The swelling ratio of the beads in different media varied according to their composition, cross-linking density (Ca2+ concentration), and pH of the aqueous medium. Thein vitro release experiment of the tetracycline-HCl encapsulated beads in different media suggests that the release of the drug is governed mainly by the swelling properties of the polymer network. The presence of PASP was found to significantly influence the swelling properties and drug release profile.