Biomedical subjects

Chi-Hwa Wang

Publications and source records attributed to Chi-Hwa Wang.

At least 19 recordsLinked to original sources

PubMed2007

Encapsulation of proteins in biodegradable polymeric microparticles using electrospray in the Taylor cone-jet mode.

Solvent extraction (or evaporation from a W(1)/O/W(2)-dispersion), coacervation, and spray drying methods are commonly employed to encapsulate protein drugs in polymeric microparticles for sustained delivery applications. To overcome the limitations of these methods, a novel electrospray method was developed to encapsulate a model protein drug-bovine serum albumin (BSA) in biodegradable polymeric microparticles and examine the feasibility of the process in not denaturing the protein. Microparticles of approximately 20 microm diameter with corrugated surfaces and smooth surfaces were observed by scanning electron microscope. Confocal laser scanning microscope images showed that BSA was distributed evenly in microparticles. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was employed to investigate the protein integrity of BSA released from the polymer matrix after 38 days. No protein degradation was observed during the 38 days release. The secondary structure of released BSA was characterized by Fourier transform infrared (FTIR) and circular dichroism (CD), which suggested that the released BSA was almost identical to native BSA. The encapsulation efficiency could reach 76% by adjusting the amount of the additive Pluronic F127 and processing parameters. The release profile could be tailored by the fabrication process and the sustained release of BSA could endure for more than 1 month. More than 80% of the bioactivity of BSA (evaluated by BSA ELISA kit) could be maintained after releasing from polymer matrix. Findings of the present study demonstrate that this novel electrospray method is a promising approach to encapsulate bioactive materials such as proteins, enzymes, antibiotics, and DNA fragments in biodegradable polymeric particles.

Absorbable Implants↗

PubMed2007

Growing tissue-like constructs with Hep3B/HepG2 liver cells on PHBV microspheres of different sizes.

In this study, an oil-in-water emulsion solvent evaporation technique was used to fabricate poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV, 8% PHV), microspheres as scaffold, to guide liver cell growth. Human hepatoma cell lines, HepG2 and Hep3B, were cultured in vitro on both the microspheres and polymer films. SEM and optical microscope images showed that multilayer cells were formed among the microspheres to bridge them together and developed into cell-construct aggregates after 1 week of culture. MTT results showed that the cell proliferation on the microspheres was more than two times higher than that on the films after 12 days of culture. The cells seeded on microspheres secreted albumin 2-4 times more than that on the positive control after 1 week of culture, which indicated that this hepatic function was greatly improved by the aggregation of cells on microspheres. Although HepG2 failed to express P-450 activity, this hepatic function was preserved when Hep3B cultured on microspheres. All the results indicated that PHBV microspheres are appropriate scaffolds for liver tissue engineering.

Cell Culture Techniques↗

PubMed2006

In vivo performance of implantable biodegradable preparations delivering Paclitaxel and Etanidazole for the treatment of glioma.

Drug-releasing implants delivering chemotherapeutic and radio-sensitizing agents are beginning to play a major role in the post-surgical eradication of residual glioma in the brain. Benefits from early arresting of tumor growth and tumor recovery dynamics stress the impact of drug release profiles of the implants on the efficacy of the treatment. This paper examines responses of BALB/c nude mice, bearing C6 glioma tumors subcutaneously, to treatments by PLGA microspheres, microparticles and discs-delivering Paclitaxel and Etanidazole. The experimental results are used to correlate the efficacy of treatment to in vitro release profiles from the various formulations. Our study demonstrates that radio-sensitizing effects during irradiation could be achieved by double burst profiles from Etanidazole-loaded discs, when compared to controls 17 days after implantation despite the short half-life of Etanidazole (1.4h) in vivo. These results also showed inhibited tumor growth on tumor volumes of 59%, 65% and 70% over the blank placebo groups after 21 days of tumor growth for spray-dried microspheres, electrohydrodynamic atomization microparticles and spray-dried discs, respectively.

Animals↗

PubMed2006

Mathematical modeling and simulation of drug release from microspheres: Implications to drug delivery systems.

This article aims to provide a comprehensive review of existing mathematical models and simulations of drug release from polymeric microspheres and of drug transport in adjacent tissues. In drug delivery systems, mathematical modeling plays an important role in elucidating the important drug release mechanisms, thus facilitating the development of new pharmaceutical products by a systematic, rather than trial-and-error, approach. The mathematical models correspond to the known release mechanisms, which are classified as diffusion-, swelling-, and erosion-controlled systems. Various practical applications of these models which explain experimental data are illustrated. The effect of gamma-irradiation sterilization on drug release mechanism from erosion-controlled systems will be discussed. The application of existing models to nanoscale drug delivery systems specifically for hydrophobic and hydrophilic molecules is evaluated. The current development of drug transport modeling in tissues utilizing computational fluid dynamics (CFD) will also be described.

Bone and Bones↗

PubMed2006

Electrohydrodynamic atomization for biodegradable polymeric particle production.

Electrohydrodynamic atomization (EHDA) has many applications such as electrospray ionization in mass spectroscopy, electrospray deposition of thin films, pharmaceutical productions, and polymeric particle fabrications for drug encapsulation. In the present study, EHDA was employed to produce biodegradable polymeric micro- and nanoparticles. The effects of processing parameters such as polymer concentration, flow rate, surfactants, organic salt, and setup configurations on the size and morphology of polymeric particles were investigated systematically. By changing the various processing parameters, controllable particle shape and size can be achieved. PLGA nanoparticles with size of around 250 nm can be obtained by using organic salts to increase the conductivity of the spraying solution even at a relatively high flow rate. A higher flow rate has the advantage of producing a stable cone spray and can be easily reproduced. Solid and porous particles can be fabricated using different experimental setups to control the organic solvent evaporation rate. Also, paclitaxel, a model antineoplastic drug, was encapsulated in polymeric particles which can be employed for controlled release applications. In short, EHDA is a promising technique to fabricate polymeric micro- or nanoparticles which can be used in drug delivery systems.

Electrochemistry↗

PubMed2006

Bubble behavior in a Taylor vortex.

We present a study on the behavior of air bubbles captured in a Taylor vortex formed in the annulus between two concentric cylinders. It is found that small bubbles stay either at certain locations near the vortex cores or in the outflow regions along the inner cylinder. If bubbles of the same size are introduced, a variety of bubble structures (such as ring, chain, cluster, etc.) appear due to different mechanisms. For bubbles of nonuniform size, orbit crossing of small and large bubbles is observed. Droplets and particles can also be captured in Taylor vortices, and these exhibit certain unique features.

Journal Article↗

PubMed2006

Microparticles developed by electrohydrodynamic atomization for the local delivery of anticancer drug to treat C6 glioma in vitro.

This study aims to fabricate biodegradable polymeric particles by electrohydrodynamic atomization (EHDA) for applications in sustained delivery of anticancer drug-paclitaxel to treat C6 glioma in vitro. Controllable morphologies such as spheres, doughnut shapes and corrugated shapes with sizes from several tens of microns to hundred nanometers of particles were observed by scanning electron microscopy (SEM) and field emission electron microscope (FSEM). The differential scanning calorimetry (DSC) study indicated that paclitaxel could be either in an amorphous or disordered-crystalline phase of a molecular dispersion or a solid solution state in the polymer matrix after fabrication. The X-ray photoelectron spectroscopy (XPS) result suggested that some amount of paclitaxel could exist on the surface layer of the microparticles. The encapsulation efficiency was around 80% and more than 30 days in vitro sustained release profile could be achieved. Cell cycling results suggested that paclitaxel after encapsulation by EHDA could keep its biological function and inhibit C6 glioma cells in G2/M phase. The cytotoxicity of paclitaxel-loaded biodegradable microparticles to C6 glioma cells could be higher than Taxol in the long-term in vitro tests evaluated by MTS assay. The drug delivery devices developed by EHDA in this study could be promising for the local drug delivery to treat malignant glioma.

Antineoplastic Agents↗

PubMed2006

Electron spin resonance microscopy applied to the study of controlled drug release.

We describe our recent developments towards 3D micron-scale imaging capability, based on electron spin resonance (ESR), and its application to the study of controlled release. The method, termed ESR microscopy (ESRM), is an extension of the conventional "millimeter-scale" ESR imaging technique. It employs paramagnetic molecules (such as stable radicals or spin-labeled drugs) and may enable one to obtain accurate 3D spatially resolved information about the drug concentration, its self-diffusion tensor, rotational correlation time and the pH in the release matrix. Theoretical calculations, along with initial experimental results, suggest that a 3D resolution of approximately 1 microm is feasible with this method. Here we were able to image successfully a high spin concentration sample with a resolution of approximately 3 x 3 x 8 microm and subsequently study a single approximately 120 microm biodegradable microsphere, internalized with a dilute solution of trityl radical, with a resolution of approximately 12.7 x 13.2 x 26 microm. Analysis of the microsphere ESR imaging data revealed a likely increase in the viscosity inside the sphere and/or binding of the radical molecule to the sphere matrix. Future directions for progress are also discussed.

Drug Delivery Systems↗

PubMed2006

In vitro and in vivo release of gentamicin from biodegradable discs.

Osteomyelitis is an infection of the bone and successful treatment involves the removal of the affected bone and the tissue by a surgical procedure following prolonged systemic and local antibiotic therapy for 4 to 6 weeks. The current local treatment is done by poly methyl methacrylate (PMMA) beads loaded with gentamicin and PMMA, being nondegradable, is to be removed by a second surgical procedure. The current study aims to develop a biodegradable composition that gives sustained release and hence reducing the need for a second surgery. Gentamicin-loaded discs were produced by compressing microparticle-gentamicin mixture obtained by spray drying a mixture of gentamicin in a solution of a biodegradable polymer. Different copolymers of poly (DL-lactic-co-glycolic acid) (PLGA) were used to study the effect of copolymer ratio and the hydrophilic-hydrophobic nature of the polymer. Theoretical drug loading up to 25% were studied and it was observed that 10% drug loading was optimum for gentamicin to be used as solid in spray drying. The results showed that about 60% of the drug is released in about 5 to 6 days and the remaining drug is released in about 30 days in total. An in vivo study was carried on rabbit femur and the local area and systemic concentration of gentamicin was monitored. It was observed that the local area concentration of gentamicin was above minimum inhibitory concentration for more than 20 days and this was also validated by computer simulations.

Animals↗

PubMed2006

Electrospun micro- and nanofibers for sustained delivery of paclitaxel to treat C6 glioma in vitro.

PURPOSE: The present study aims to develop electrospun PLGA-based micro- and nanofibers as implants for the sustained delivery of anticancer drug to treat C6 glioma in vitro. METHODS: PLGA and an anticancer drug--paclitaxel-loaded PLGA micro- and nanofibers were fabricated by electrospinning and the key processing parameters were investigated. The physical and chemical properties of the micro- and nanofibers were characterized by various state-of-the-art techniques, such as scanning electron microscope and field emission scanning electron microscope for morphology, X-ray photoelectron spectroscopy for surface chemistry, gel permeation chromatogram for molecular weight measurements and differential scanning calorimeter for drug physical status. The encapsulation efficiency and in vitro release profile were measured by high performance liquid chromatography. In addition, the cytotoxicity of paclitaxel-loaded PLGA nanofibers was evaluated using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide MTT) assay on C6 glioma cell lines. RESULTS: PLGA fibers with diameters of around several tens nanometers to 10 microm were successfully obtained by electrospinning. Ultrafine fibers of around 30 nm were achieved after addition of organic salts to dilute polymer solution. The encapsulation efficiency for paclitaxel-loaded PLGA micro- and nanofibers was more than 90%. DSC results suggest that the drug was in the solid solution state in the polymeric micro- and nanofibers. In vitro release profiles suggest that paclitaxel sustained release was achieved for more than 60 days. Cytotoxicity test results suggest that IC50 value of paclitaxel-loaded PLGA nanofibers (36 microg/ml, calculated based on the amount of paclitaxel) is comparable to the commercial paclitaxel formulation-Taxol. CONCLUSIONS: Electrospun paclitaxel-loaded biodegradable micro- and nanofibers may be promising for the treatment of brain tumour as alternative drug delivery devices.

Antineoplastic Agents, Phytogenic↗

PubMed2005

Simulation of gentamicin delivery for the local treatment of osteomyelitis.

In order to understand the effect of antibiotics delivery to bone tissue, by biodegradable polymeric drug disc, for the treatment of osteomyelitis, a three-dimensional simulation model is developed. The simulation investigates the effect of pressure-induced convection on drug distribution, by taking into account the pressure gradient that exists between capillaries and interstitial space, and also as a result of the surgical opening. The clotting process at the surgical opening is incorporated into the simulation, and the effect of clotting duration is investigated. The clotting duration for the baseline simulation is 2 days and it is observed that increasing this duration depresses the mean drug concentration in the marrow and cortical bone. The effect of double burst release profile is also studied and it is observed that drug concentration drops too rapidly after the first burst to provide any therapeutic effect. However, it is shown that the drug concentration after the second burst stays above the minimum inhibitory concentration of the bacteria for a longer period of time, than would have been observed for a mono-burst release. Inserting non-biodegradable polymethylmethacrylate (PMMA) beads into bone seems to cause a higher average concentration of drug in the marrow. However, this could be brought about by the difference in the geometry between the disc and the bead, and the amount of drug packed in each bead. Further simulations on the management of dead space shows the ineffectiveness of having the void filled up with surgical gel as it becomes an additional barrier to drug delivery to the infected tissues.

Animals↗

PubMed2005

Self-assembled biodegradable nanoparticles developed by direct dialysis for the delivery of paclitaxel.

PURPOSE: The main objective of this study was to obtain self-assembled biodegradable nanoparticles by a direct dialysis method for the delivery of anticancer drug. The in vitro cellular particle uptake and cytotoxicity to C6 glioma cell line were investigated. METHODS: Self-assembled anticancer drugs--paclitaxel-loaded poly(D,L-lactic-co-glycolic acid) (PLGA) and poly(L-lactic acid) (PLA) nanoparticles--were achieved by direct dialysis. The physical and chemical properties of nanoparticles were characterized by various state-of-the-art techniques. The encapsulation efficiency and in vitro release profile were measured by high-performance liquid chromatography. Particle cellular uptake was studied using confocal microscopy, microplate reader, and flow cytometry. In addition, the cytotoxicity of this drug delivery system was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on C6 glioma cell line to predict the possible dose response of paclitaxel-loaded PLGA and PLA nanoparticles. RESULTS: PLGA and PLA nanoparticles with or without vitamin E tocopherol polyethylene glycol succinate (TPGS) as an additive were obtained, in which the sustained release of paclitaxel of more than 20 days was achieved. The coumarin6-loaded PLGA and PLA nanoparticles could penetrate the C6 glioma cell membrane and be internalized. The cytotoxicity of paclitaxel-loaded nanoparticles seemed to be higher than that of commercial Taxol after 3 days incubation when paclitaxel concentrations were 10 and 20 microg/ml. CONCLUSIONS: Direct dialysis could be employed to achieve paclitaxel-loaded PLGA and PLA nanoparticles, which could be internalized by C6 glioma cells and enhance the cytotoxicity of paclitaxel because of its penetration to the cytoplasm and sustained release property.

Antineoplastic Agents, Phytogenic↗

PubMed2005

Fabrication of double-walled microspheres for the sustained release of doxorubicin.

Double-walled microspheres with poly(L-lactic acid) shells and poly(DL-lactic-co-glycolic acid) cores were fabricated using solvent evaporation technique which involves the phase separation phenomenon of a binary composite of these two polymers. Doxorubicin, a hydrophilic drug, was entrapped within the core of these double-walled microspheres with different core-shell thicknesses and compositions to investigate the in vitro release on this class of microspheres. Microspheres of different size ranging from 50 to 300 microm were also fabricated to investigate whether this method is suitable for fabricating small particles for intramuscular injection applications, and their phase separation and surface morphology were examined by differential scanning calorimetry, scanning electron microscopy, and optical microscopy.

Antibiotics, Antineoplastic↗

PubMed2005

Fabrication of monodispersed Taxol-loaded particles using electrohydrodynamic atomization.

In the fabrication of controlled drug release matrix, monodispersed particle sizes are usually preferred as they give a more uniform and precisely controlled release profile. Electrohydrodynamic atomization (EHDA) [J.C. Ijsebaert, K.B. Geerse, J.C.M. Marijnissen, J.W.J Lammers, P. Zannen, Electro-Hydrodynamic atomization of drug solutions for inhalation purposes, J. Appl. Physiol. 91(2001), 2735-2741.] is a method that can potentially produce particles with very low polydispersity. In the present work, Taxol-loaded poly-caprolactone (PCL) particles were fabricated using EHDA. Effort was undertaken to investigate the cause of the low yield of EHDA and to improve it to around 80%. This was achieved by increasing the ventilation and properly discharging the residual charges on the particulate cake at the filter paper. A phase Doppler particle analyzer (PDPA) was used to detect the spray modes of EHDA and the optimum operating conditions were determined. With differential scanning calorimetry (DSC), the uniformity of drug and polymer matrix is investigated. Moderate zeta potential values together with laser confocal micrographs give a possible explanation for the in vitro cell uptake data. These results are substantiated by a reasonably high encapsulation efficiency (EE) and sustained release profiles over 1-month period. The EHDA method is shown to be a potentially suitable technique to prepare close to monodispersed drug release particles.

Antineoplastic Agents, Phytogenic↗

PubMed2005

Gentamicin-loaded discs and microspheres and their modifications: characterization and in vitro release.

Osteomyelitis is an infection of the bone, and successful treatment involves local administration for about 6 weeks. Gentamicin is a very hydrophilic drug and tends to come out into the water phase when microspheres are fabricated using solvent evaporation method. Hence, spray drying is an option, and it was observed that the release rate tends to be fast when the particle size is small and large particles cannot be prepared by spray drying. In an effort to get better encapsulation efficiency and release rate, we have worked on the possibility of compressing the microspheres into discs and modifying the porosity of the discs by using biocompatible materials like polyethylene glycol (PEG) and calcium phosphates and also on the fabrication of double-walled and composite microspheres. In the case of microspheres, two methods of fabrication both based on solvent evaporation method were employed. The two polymers used are poly-L-lactide (PLLA) and copolymers of poly-DL-lactic-co-glycolic acid (PLGA). One method is based on the spreading coefficient theory for the formation of double-walled microspheres by using single solvent, while the other is based on the property of PLLA not being soluble in ethyl acetate (EA). Characterization to check if the microspheres formed are double-walled was performed. The fabrication method where two solvents, dichloromethane (DCM) and ethyl acetate, were used gave double-walled microspheres, while the other where only dichloromethane was used gave composites. The double-walled microspheres were smaller in size compared to the composites, which were in the range of 100-600 microm. This can be attributed to the difference in the fabrication procedure. We were able to achieve better encapsulation efficiencies of more than 50% and slower release rates, which lasted for about 15 days. It was observed that size played a major role in the encapsulation efficiency and release rates. The possibility of achieving better results by studying the effect of concentration of polymer in solvent and the effect of using different polymers was investigated.

Anti-Bacterial Agents↗

PubMed2005

In vitro study of anticancer drug doxorubicin in PLGA-based microparticles.

Doxorubicin (DOX), also known as adriamycin, is an anthracycline drug commonly used in cancer chemotherapy. Unfortunately, its therapeutic potential has been restricted by its dose limited cardiotoxicity and the resistance developed by the tumor cells to the molecule after some time of treatment. One way to overcome these problems is to encapsulate the drug in poly (D, L-lactide-co-glycolide) (PLGA) microparticles. This paper investigates the release characteristics of DOX from polymeric carriers fabricated using the spray-drying technique. The encapsulation efficiency, size and morphology of the various polymeric devices were also determined. In order to improve the release characteristics, Pluronic P105 (PLU) and poly (L-Lactide) (PLLA) are individually used in combination with PLGA. Finally, a cytotoxicity test was performed using Glioma C6 cancer cells to investigate the cytotoxicity of DOX delivered from PLGA microparticles. It has been found that the cytotoxicity of DOX to Glioma C6 cancer cells is enhanced when DOX is delivered from PLGA polymeric carrier.

Animals↗

PubMed2004

Stabilization and encapsulation of human immunoglobulin G into biodegradable microspheres.

The instability of protein during preparation, storage, and release has become a major concern in recent years in the encapsulation of proteins into biodegradable polymers for controlled release systems. The present investigation was performed to study the mechanism of degradation of human immunoglobulin G (IgG) in double emulsion and solid-in-oil-in-water (S/O/W) encapsulation processes. The stabilizing effects of various excipients during the period of protein atomization using spray freeze-drying and subsequent encapsulation into polylactide-co-glycolide (PLGA) microspheres were explored. The size-exclusion high-performance liquid chromatography (SEC-HPLC) results showed that ultrasonication did not change the primary structure of IgG significantly. However, enzyme-linked immunosorbent assay (ELISA) revealed that the subsequent double-emulsion solvent evaporation process denatured nearly 80% of the total amount of IgG. This was possibly due to the adsorption, unfolding, and aggregation of IgG at the water/organic solvent interface. Both mannitol and trehalose could stabilize IgG during spray freeze-drying, with over 90% retention of its molecular integrity and immunoactivity, which were verified using SEC-HPLC and ELISA. Solid protein microparticles were further entrapped into monolithic-type microspheres of PLGA using the S/O/W method. FTIR results suggested that the incomplete release that is often observed in the formulation of controlled protein release systems may be due to the degradation or aggregation of protein in the solid polymer matrix.

Biodegradation, Environmental↗

PubMed2003

Cake consolidation in a compression-permeability cell: effect of side-wall friction.

A simulation study was made to investigate the transient state stresses, strains, and void ratio distributions in the formation of a filter cake in a compression-permeability cell (C-P cell). A finite-element software package, ABAQUS, was used for the simulation and emphasis was placed on the effect of the cake/cell-surface friction. The validity of the simulation was assessed by comparing simulation results with available experimental data.

Journal Article↗