Biomedical subjects

Kinam Park

Publications and source records attributed to Kinam Park.

At least 19 recordsLinked to original sources

PubMed2007

Drug release properties of polymer coated ion-exchange resin complexes: experimental and theoretical evaluation.

Although ion-exchange resins have been used widely as drug delivery systems, their exact release kinetics has not been reported yet. Usually only the rate-limiting step has been taken into account and the rest of the steps have been ignored as instantaneous processes. To investigate the exact release kinetics of polymer-coated drug/ion-exchange resin complexes for sustained drug delivery, the results of new mathematical modeling were compared with experimental results. Drug/resin complexes with a model drug, dextromethorphan, were prepared and used as cores for fluid-bed coating. An aqueous colloidal dispersion of poly(vinyl acetate) was applied for the coating. A comprehensive mathematical model was developed using a mechanistic approach by considering diffusion, swelling, and ion-exchange processes solved by numerical techniques. The rate-limiting factor of the uncoated resin particles was diffusion through the core matrix. Similarly, in the coated particles the rate-limiting factor was diffusion through the coating membrane. The mathematical model has captured the phenomena observed during experimental evaluations and the release dynamics from uncoated and coated (at different coat levels) particles were predicted accurately (maximum RMSE 2.4%). The mathematical model is a useful tool to theoretically evaluate the drug release properties from coated ion-exchange complexes thus can be used for design purposes.

Anion Exchange Resins↗

PubMed2007

Hydrotropic polymeric micelles for enhanced paclitaxel solubility: in vitro and in vivo characterization.

The purpose of this investigation was to characterize the in vitro stability and in vivo disposition of paclitaxel in rats after solubilization of paclitaxel into hydrotropic polymeric micelles. The amphiphilic block copolymers consisted of a micellar shell-forming poly(ethylene glycol) (PEG) block and a core-forming poly(2-(4-vinylbenzyloxy)-N,N-diethylnicotinamide) (P(VBODENA)) block. N,N-Diethylnicotinamide (DENA) in the micellar inner core resulted in effective paclitaxel solubilization and stabilization. Solubilization of paclitaxel using polymeric micelles of poly(ethylene glycol)-b-P(D,L-lactide) (PEG-b-PLA) served as a control for the stability study. Up to 37.4 wt % paclitaxel could be loaded in PEG-b-P(VBODENA) micelles, whereas the maximum loading amount for PEG-b-PLA micelles was 27.6 wt %. Thermal analysis showed that paclitaxel in the polymeric micelles existed in the molecularly dispersed amorphous state even at loadings over 30 wt %. Paclitaxel-loaded hydrotropic polymeric micelles retained their stability in water for weeks, whereas paclitaxel-loaded PEG-b-PLA micelles precipitated in a few days. Hydrotropic polymer micelles were more effective than PEG-PLA micelle formulations in inhibiting the proliferation of human cancer cells. Paclitaxel in hydrotropic polymer micelles was administered orally (3.8 mg/kg), intravenously (2.5 mg/kg), or via the portal vein (2.5 mg/kg) to rats. The oral bioavailability was 12.4% of the intravenous administration. Our data suggest that polymeric micelles with a hydrotropic structure are superior as a carrier of paclitaxel due to a high solubilizing capacity combined with long-term stability, which has not been accomplished by other existing polymeric micelle systems.

Administration, Oral↗

PubMed2006

In situ visualization of paclitaxel distribution and release by coherent anti-Stokes Raman scattering microscopy.

Visualization of three-dimensional distribution of drug molecules and subsequent changes during the release process is critical for understanding drug delivery mechanisms as well as designing tailor-made release profiles. This study utilized coherent anti-Stokes Raman scattering (CARS) imaging to examine paclitaxel distribution in various polymer films with lateral resolution of 0.3 microm and depth resolution of 0.9 microm. Raman bands in the CH stretch vibration and fingerprint regions were used to distinguish paclitaxel from the polymers. The detection sensitivity was measured to be 29 mM by imaging paclitaxel molecules dissolved in N,N-dimethylformamide solution. Release of paclitaxel from a polymer matrix was monitored at an acquisition speed of 1 frame/s. Our results show that CARS microscopy can be used effectively for in situ imaging of native drug molecules in a delivery system.

Microscopy↗

PubMed2006

Elastic, superporous hydrogel hybrids of polyacrylamide and sodium alginate.

A novel approach was developed to prepare a superporous hydrogel with superior mechanical and elastic properties. According to this method, a synthetic monomer was polymerized and crosslinked in the presence of a water-soluble alginate polymer. Later in the process, the alginate part of the synthesized hydrogel was treated with metal cations, which resulted in a hydrogel hybrid with an interpenetrating network structure. In this article, a hydrogel hybrid of acrylamide and alginate is highlighted because of its unique swelling and mechanical properties. This hydrogel hybrid shows resilience and a rubbery property in its fully water-swollen state, which not previously been reported. To help understand the underlying mechanism responsible for such unique properties with hydrogel hybrids, the ionotropic gelation of the alginate polymer was also studied in more detail.

Acrylic Resins↗

PubMed2006

Modeling film-coat non-uniformity in polymer coated pellets: a stochastic approach.

The objective of the present study is to include coating thickness non-uniformity in the development of a drug release model using coated ion-exchange pellets through the use of stochastic approaches. Drug release from ion-exchange resins was described using a Nernst-Plank model. Complexes of a model drug (dextromethorphan) and Dowex 50WX4-200 were prepared using a modified batch method and coated with Kollicoat SR 30D polymer. The deterministic model, validated using experimental drug release profiles for different coating thicknesses at 0%, 10%, 15%, 20% (w/w), was in agreement with the experimental data with a maximum root mean square error (RMSE) of 2.4%. An arbitrary Lagrangian-Eulerian approach was pursued to develop models of spherical pellets with non-uniform coating thicknesses. The Monte Carlo method was used to simulate the effect of the level of coating deformity on the cumulative drug release profile. Considering the co-existence of equal percentages of deformed and undeformed pellets in a batch, the cumulative release profile can vary by approximately +/-6% as a result of coating non-uniformity. The release profile obtained for a model of an arbitrary pellet with an actual non-uniform coating profile was in good agreement with the average release profile for the models of the theoretical randomly deformed pellets. The developed mathematical model is a useful tool to evaluate and predict release profiles of polymer coated ion-exchange resin complexes.

Algorithms↗

PubMed2006

Mechanisms of controlled drug release from drug-eluting stents.

The clinical importance of drug-eluting stents (DESs) has been demonstrated by their unparalleled success in preventing restenosis after stenting procedures. The magnitude of success is historic despite their short history. The current DESs deliver a single drug aiming to prevent or minimize proliferation of smooth muscle cells. Since the restenosis process involves several different biological responses, the ability to deliver the right drugs at the right times is critical for further development of the second generation of DESs. As the type of drugs that can be delivered from DESs varies, it is imperative to understand the drug delivery mechanisms and the approaches available for drug coating on the stents. The drug delivery mechanisms of current DESs that have been used clinically and under clinical trials are explained.

Coronary Restenosis↗

PubMed2006

Preparation and swelling behavior of chitosan-based superporous hydrogels for gastric retention application.

Chitosan and glycol chitosan hydrogels were prepared, and their swelling behaviors in acidic solution were studied to investigate their application for gastric retention device. The optimum preparation condition of superporous hydrogels was obtained from the gelation and blowing kinetics measured at varying acidic conditions. Both the swelling rate and swelling ratio of glycol chitosan hydrogels were higher than those of chitosan hydrogels. Swelling behaviors were significantly affected by not only foaming/drying methods but also crosslinking density, as the sizes and structures of pores generated were highly dependent on those preparation conditions. The prepared superporous hydrogels were highly sensitive to pH of swelling media, and showed reversible swelling and de-swelling behaviors maintaining their mechanical stability. The degradation kinetics in simulated gastric fluid was also studied.

Biocompatible Materials↗

PubMed2005

Fast-melting tablets based on highly plastic granules.

Highly plastic granules that can be compressed into tablets at low pressure were developed to make fast-melting tablets (FMTs) by compression method. The highly plastic granules are composed of three components: a plastic material, a material enhancing water penetration, and a wet binder. One of the unique properties of the highly plastic granules is that they maintain a porous structure even after compression into tablets. The porous and plastic nature of the granules allows fast absorption of water into the compressed tablet for fast melting/dissolution of the tablet. The prepared tablets possess tablet strength and friability that are suitable for multi-tablet packages. The three-component highly plastic granules provide an effective way of making FMTs by compression.

Chemistry, Pharmaceutical↗

PubMed2005

Hydrogen bonding interactions between adsorbed polymer molecules and crystal surface of acetaminophen.

The objective of this work was to investigate whether or not the hydrogen bonding interaction between polymer and crystal surface can be detected by the etching pattern changes in the presence of polymers. The (010) face of acetaminophen single crystal was used as a model solid surface. The etching patterns on the (010) face of acetaminophen crystal by water are in the directions of a- and c-axes, which are the same as the directions of the dominant attachment energies on the (010) face. In the presence of polymer, the hydrogen bonding interactions between adsorbed polymer and crystal surface can affect surface diffusion of acetaminophen molecules and change the etching patterns in the direction of a-axis, i.e., the direction of one hydrogen bond chain. Studies with 2-hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC) and poly(vinyl alcohol) (PVA) showed that polymers, which can form hydrogen bonds with acetaminophen crystal surface, can change etching patterns in the direction of a-axis. Study with Dextran suggested that if a polymer cannot form hydrogen bonds with crystal surface due to steric repulsion, it will not change the etching pattern in the direction of a-axis. Studies with poly(ethylene glycol) (PEG) and poly(propylene glycol) (PPG) further confirmed that only if a polymer can form hydrogen bonds with acetaminophen on crystal surface, the etching patterns in the direction of a-axis will be affected. The study results suggest that in the presence of polymers, the etching pattern change in the direction of hydrogen bond chain, the a-axis of acetaminophen crystals, can be used to indicate the existence of the hydrogen bonding interactions between adsorbed polymers and acetaminophen crystal surface.

Acetaminophen↗

PubMed2005

Bioadhesive interaction and hypoglycemic effect of insulin-loaded lectin-microparticle conjugates in oral insulin delivery system.

Biodegradable microparticles were prepared with alginate by the piezoelectric ejection process, and lectin (wheat germ agglutinin, WGA) was conjugated to alginate microparticles to take advantage of the protective effects of alginate microparticles and the mucoadhesive properties of WGA for improved oral delivery of insulin. Their specific interaction with model mucin was determined by pig mucin (PM) immobilized surface plasmon resonance (SPR) biosensor and in vitro adsorption studies. The hypoglycemic effects of alginate and WGA-conjugated alginate microparticles were examined after oral administration in streptozotocin-induced diabetic rats. The alginate microparticles were fabricated by ejecting alginate/insulin solution into 0.1 M CaCl2 solution through a nozzle actuated by the piezoelectric transducer. The WGA was conjugated to alginate microparticles by activating hydroxyl groups with carbonyldiimidazole (CDI). The affinity constant (K(A)) of alginate-WGA microparticles from the SPR data (K(A)=5.455 g(-1) L) was about nine times greater than alginate microparticles (K(A)=0.628 g(-1) L). In vitro experiments in the mucin solution showed that the conjugated WGA enhanced the interaction about three times. In vivo studies with diabetic rats showed that the blood glucose level of SPF rats was lowest when alginate-WGA microparticles were orally administered. Larger K(A) of alginate-WGA microparticles resulted in larger glucose change (%) from base level. Still, it is not clear whether the transport of insulin through the intestinal mucous membrane was influenced by the increase of residence time at intestinal membrane through the specific adsorption of WGA-conjugated microparticles. However, it is concluded that alginate-WGA microparticles enhance the intestinal absorption of insulin sufficient to drop the glucose level of blood.

Adhesives↗

PubMed2005

Advances in superporous hydrogels.

Superporous hydrogels (SPHs) are different from superabsorbent polymers (SAPs) in that SPHs swell fast, within minutes, to the equilibrium swollen state regardless of their size. The fast swelling property is based on water absorption through open porous structure by capillary force. The poor mechanical strength of SPHs was overcome by developing the second-generation SPH composites (SPHCs) and the third-generation SPH hybrids (SPHHs). This review examines the differences between SAPs and SPHs and describes three different generations of SPHs.

Chemistry, Pharmaceutical↗

PubMed2005

Hydrotropic polymer micelle system for delivery of paclitaxel.

Hydrotropic polymer micelle system has been developed for delivery of poorly water-soluble drugs such as paclitaxel. Hydrotropic polymers based on N,N-diethylnicotinamide were synthesized and used as a hydrophobic block for constructing amphiphilic block copolymers. The hydrotropic block copolymers self-assembled to form micelles in aqueous media. The size of the prepared polymer micelles was in the range of 30-50 nm, and increased to 100-120 nm after paclitaxel loading. The critical micelle concentrations (CMCs) of the block copolymers were higher by an order of magnitude than those of other typical polymer micelles, due to less hydrophobicity of the hydrotropic blocks. The drug loading capacity and physical stability of the polymer micelles were characterized and compared with those of other polymer micelles. The hydrotropic polymer micelles containing hydrotrope-rich cores showed not only higher loading capacity but also enhanced physical stability in aqueous media. They could be redissolved in aqueous media by simple vortexing and/or a mild heating. The hydrotropic polymer micelles provide an alternative approach for formulation of poorly soluble drugs.

Drug Delivery Systems↗

PubMed2005

Study on the interactions between polyvinylpyrrolidone (PVP) and acetaminophen crystals: partial dissolution pattern change.

The objective of the study was to investigate the interactions between polyvinylpyrrolidone (PVP) and acetaminophen crystal especially on crystal surface. The effects of PVP on the etching pattern change of the acetaminophen (010) face, solubility enhancement as well as the intrinsic dissolution rate (IDR) of acetaminophen crystals have been studied. The etching patterns of the acetaminophen (010) face in the presence of PVP have stable ledges in the direction of a-axis, but deviate from c-axis, which shows that the dissolution on the (010) face has been affected by the adsorbed PVP especially in the direction of c-axis through van der Waals interactions rather than hydrogen bonding interactions. Even though PVP(K30) can enhance the solubility of acetaminophen in concentration higher than 1 mg/mL, the IDR of acetaminophen in diluted PVP solutions was lower than in water. Because the viscosity of those diluted PVP(K30) solutions were the same as water viscosity, the lowered IDR of acetaminophen cannot be explained simply by the viscosity effects of PVP solutions. Overall, the study suggests that the PVP molecules adsorbed on the surface of acetaminophen crystals play an important role in etching pattern change as well as the intrinsic dissolution rate change.

Acetaminophen↗

PubMed2005

Accelerated chondrocyte functions on NaOH-treated PLGA scaffolds.

Compared to conventional poly(lactic-co-glycolic acid) (PLGA), previous studies have shown that NaOH-treated PLGA two-dimensional substrates enhanced functions of osteoblasts (bone-forming cells), vascular and bladder smooth muscle cells, and chondrocytes (cartilage-synthesizing cells). In this same spirit, the purpose of this in vitro study was to fabricate three-dimensional NaOH-treated PLGA scaffolds and determine their efficacy toward articular cartilage applications. To improve functions of chondrocytes including their adhesion, growth, differentiation, and extracellular matrix synthesis, PLGA scaffolds were modified via chemical etching techniques using 1N NaOH for 10 min. Results demonstrated that NaOH-treated PLGA three-dimensional scaffolds enhanced chondrocyte functions compared to non-treated scaffolds. Specifically, chondrocyte numbers, total intracellular protein content, and the amount of extracellular matrix components (such as glycosaminoglycans and collagens) were significantly greater on NaOH-treated than on non-treated PLGA scaffolds. Underlying material properties that may have enhanced chondrocyte functions include a more hydrophilic surface (due to hydrolytic degradation of PLGA by NaOH), increased surface area, altered porosity (both percent and diameter of individual pores), and a greater degree of nanometer roughness. For these reasons, this study adds a novel tissue-engineering scaffold to the cartilage biomaterial community: NaOH-treated PLGA. Clearly, such modifications to PLGA may ultimately enhance the efficacy of tissue-engineering scaffolds for articular cartilage repair.

Biocompatible Materials↗

PubMed2005

Frosta: a new technology for making fast-melting tablets.

The fast-melting tablet (FMT) technology, which is known to be one of the most innovated methods in oral drug delivery systems, is a rapidly growing area of drug delivery. The initial success of the FMT formulation led to the development of various technologies. These technologies, however, still have some limitations. Recently, a new technology called Frosta (Akina) was developed for making FMTs. The Frosta technology utilises the conventional wet granulation process and tablet press for cost-effective production of tablets. The Frosta tablets are mechanically strong with friability of < 1% and are stable in accelerated stability conditions when packaged into a bottle container. They are robust enough to be packaged in multi-tablet vials. Conventional rotary tablet presses can be used for the production of the tablets and no other special instruments are required. Thus, the cost of making FMTs is lower than that of other existing technologies. Depending on the size, Frosta tablets can melt in < 10 s after placing them in the oral cavity for easy swallowing. The Frosta technology is ideal for wide application of FMTs technology to various drug and nutritional formulations.

Administration, Oral↗

PubMed2004

A new microencapsulation method using an ultrasonic atomizer based on interfacial solvent exchange.

Reservoir-type microcapsules were produced in a mild and highly efficient manner using a coaxial ultrasonic atomizer. To understand the microencapsulation mechanism, the atomizer was operated in different modes. The results suggested the reservoir-type microcapsules were formed by midair collision of the microdrops of the two component liquids consisting of a polymer solution and an aqueous solution. The encapsulation efficiency and the distribution of the microdrops captured in midair were dependent on the ratio of the flow rates of the two liquids, which suggested that the collision involved multiple microdrops. This method allowed lysozyme to be encapsulated without loss of functional integrity and to be released with near zero-order kinetics for over 50 days. The ultrasonic atomizer provided a new method of preparing reservoir-type microcapsules.

Anti-Infective Agents↗

PubMed2004

Characterization of reservoir-type microcapsules made by the solvent exchange method.

The purpose of this research was to characterize and optimize the properties of microcapsules produced by the solvent exchange method, a new microencapsulation technique. Reservoir-type microcapsules containing lysozyme as a model protein were produced using a coaxial ultrasonic atomizer under various formulation and instrument settings, and characterized with respect to in vitro release kinetics and stability of the encapsulated protein. The solvent exchange method could encapsulate protein drugs with high efficiency under an optimized condition and was mild enough to preserve the integrity of the encapsulated lysozyme during the process. In vitro release studies showed that the microcapsules could release proteins in a controllable manner. The solvent exchange method is a mild and simple microencapsulation method that could encapsulate lysozyme, maintaining its functional integrity.

Capsules↗

PubMed2004

Hydrotropic agents for study of in vitro paclitaxel release from polymeric micelles.

A new experimental method for in vitro release studies of poorly soluble drugs from polymeric micelle systems was developed using a hydrotropic agent, sodium salicylate. It is difficult to maintain a good sink condition for poorly water-soluble drugs, such as paclitaxel (PTX), because of their low aqueous solubility. In this study, a good sink condition for PTX was achieved by using aqueous sodium salicylate solution which solubilized more than 10 times the total amount of PTX incorporated in polymeric micelles. Sodium salicylate at 1 M concentration increased the aqueous PTX solubility by 100 times without destroying the micellar structure of poly(ethylene glycol)-block-poly(phenylalanine) (PEG-b-PPhe) copolymer. PTX was continuously released from PEG-b-PPhe micelles in the hydrotropic release medium. The hydrotropic solution presents a simple method for studying in vitro release behavior of poorly soluble drugs from polymeric micelles in aqueous media.

Antineoplastic Agents, Phytogenic↗