Dae-duk Kim - Academia.edu (original) (raw)

Papers by Dae-duk Kim

Journal of Pharmaceutical Investigation, 2012

Spray-dried microspheres based on polysaccharides were developed and the conformational stability... more Spray-dried microspheres based on polysaccharides were developed and the conformational stability and controlled release of incorporated protein were evaluated using bovine serum albumin (BSA) as a model protein. Microspheres composed of water soluble chitosan (WCS), hydroxypropyl-b-cyclodextrin (HP-b-CD) and polyethylene glycol (PEG) were prepared by spray dying. WCS was used as a mucoadhesive and biocompatible polymer. HP-b-CD and PEG were used as protein stabilizer during the spray drying process. Microspheres with 6-7 lm of mean diameter were successfully developed. Encapsulation efficiency of BSA in microsphere was over 70 %. Primary, secondary and tertiary structure of incorporated BSA in microsphere was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, circular dichroism, and fluorescence intensity measurement, respectively. Conformational stability of BSA was maintained during the spray drying process. BSA release from microspheres was evaluated in in vitro model using the Transwell Ò insert, and showed a sustained release profile compared to naive BSA. Thus, these microspheres could possibly serve as an optimized delivery system for preserved stability and sustained release of protein.

Journal of Pharmaceutical Investigation, 2013

The prevalence of obesity has soared in recent decades, and now is considered as a worldwide prob... more The prevalence of obesity has soared in recent decades, and now is considered as a worldwide problem, with significant health and medical implications. Obesity is often linked to several co-morbidities including diabetes, cardiovascular diseases, and cancers, and a number of drugs are available for the treatment of these diseases. Moreover, obesity can affect various physiological factors including plasma proteins, drug metabolizing enzymes, drug transporters, and blood flow, thereby altering drug absorption, distribution, metabolism, and excretion (ADME). Therefore, information regarding obesity-related physiological changes and their pharmacokinetic consequences is crucial for understanding pharmacokinetics and optimizing drug therapy in obese population. Herein, this article reviews the effects of obesity on physiological factors determining drug ADME and their pharmacokinetic consequences. In addition, a brief summary on animal models of obesity is presented.

Studies in Mechanobiology, Tissue Engineering and Biomaterials, 2010

Reconstitution of the articular cartilage tissue can be achieved by cell delivery techniques. How... more Reconstitution of the articular cartilage tissue can be achieved by cell delivery techniques. However, an optimal procedure exhibiting minimal toxicity and maximum therapeutic efficacy is still to be developed. The two most common cell types that are being investigated for the treatment of osteoarthritis are chondrocytes and mesenchymal stem cells which need to be formulated with the proper signaling molecules

Biotechnology: Pharmaceutical Aspects, 2008

An improved PEGylated liposomal formulation of paclitaxel has been developed with the purpose of ... more An improved PEGylated liposomal formulation of paclitaxel has been developed with the purpose of improving the solubility of paclitaxel as well as the physicochemical stability of liposome in comparison to the current Taxol® formulation. The use of 3% (v/v) Tween 80 in the hydration media was able to increase the solubility of drug. The addition of sucrose as a lyoprotectant

PLOS ONE, 2015

Oral solid formulations based on Angelica gigas Nakai (AGN) and Soluplus were prepared by the hot... more Oral solid formulations based on Angelica gigas Nakai (AGN) and Soluplus were prepared by the hot-melting extrusion (HME) method. AGN was pulverized into coarse and ultrafine particles, and their particle size and morphology were investigated. Ultrafine AGN particles were used in the HME process with high shear to produce AGN-based formulations. In simulated gastrointestinal fluids (pH 1.2 and pH 6.8) and water, significantly higher amounts of the major active components of AGN, decursin (D) and decursinol angelate (DA), were extracted from the HME-processed AGN/Soluplus (F8) group than the AGN EtOH extract (ext) group (p < 0.05). Based on an in vivo pharmacokinetic study in rats, the relative oral bioavailability of decursinol (DOH), a hepatic metabolite of D and DA, in F8-administered mice was 8.75-fold higher than in AGN EtOH ext-treated group. In scopolamine-induced memory-impaired mice, F8 exhibited a more potent cognitive enhancing effect than AGN EtOH ext in both a Morris water maze test and a passive avoidance test. These findings suggest that HME-processed AGN/Soluplus formulation (F8) could be a promising therapeutic candidate for memory impairment.

Biopharmaceutics & drug disposition, Jan 21, 2015

The pharmacokinetics of lobeglitazone (LB) was studied after intravenous administration of a dose... more The pharmacokinetics of lobeglitazone (LB) was studied after intravenous administration of a dose at 1 mg/kg and oral administration of doses at 0.1, 1 and 10 mg/kg in male and female rats. The area under the plasma concentration-time curve from time zero to infinity (AUCinf ) after intravenous administration was approximately 7.1 times higher in female rats than in male rats. In addition, the AUCinf in the case of oral administration was at least 4.4 times higher in female rats and appeared to increase in proportion to the dose in both genders. The in vitro half-lives were 18.8 ± 4.45 min and 60.7 ± 11.2 min, as evidenced by incubating liver microsomes obtained from male and female rats, respectively. As a result, the estimated CLint for LB for male rat liver microsomes (0.0779 ± 0.0233 mL/min/mg protein) was much higher than that for female rat liver microsomes (0.0233 ± 0.0039 mL/min/mg protein, p < 0.05). These observations suggest that there are gender differences in the pha...

International journal of pharmaceutics, Jan 18, 2015

Poly(d,l-lactic acid)-glycerol (PDLLA-G)-based nanoparticles (NPs) were fabricated for the intrav... more Poly(d,l-lactic acid)-glycerol (PDLLA-G)-based nanoparticles (NPs) were fabricated for the intravenous delivery of curcumin (CUR). NPs with a mean diameter of approximately 200nm, a narrow size distribution, and capable of efficient drug encapsulation were prepared using an emulsification-solvent evaporation method. The stability of NPs was verified in water, phosphate buffered saline (PBS), and serum after 24-h incubation. A sustained drug release pattern was observed, and the amount of CUR released in acidic media (pH 5.5) was higher than in media at physiological pH (pH 7.4). Blank NPs (without drug loading) did not exhibit severe cytotoxicity in MDA-MB-231 human breast adenocarcinoma cells. The in vitro anti-tumor efficacy of CUR-loaded NPs in MDA-MB-231 cells was comparable to that of a solution of CUR. Pharmacokinetic studies in rats showed that the in vivo clearance (CL) of CUR in the NP-treated group was lower than the group treated with CUR solution. Therefore, encapsulatio...

Journal of Pharmaceutical Investigation, 2012

Transport studies of model drugs were conducted across the human nasal epithelial (HNE) and norma... more Transport studies of model drugs were conducted across the human nasal epithelial (HNE) and normal human bronchial epithelial (NHBE) cell monolayers cultured by air-liquid interface method. Physicochemical properties (e.g., molecular weight, calculated partition coefficient, dose number) of model drugs were quoted from literatures and apparent permeability coefficients (P app ) across the HNE and NHBE cell monolayers were directly measured. A linear relationship was observed between the P app values of model drugs in the HNE and NHBE cell monolayers. As the molecular weight of model drugs increased, the P app showed a decreasing pattern while the increase of partition coefficients resulted in the increment of P app . These results indicated that the transport of model drugs across both cell monolayers followed mainly the passive diffusion mechanism, although substrates mediated by drug transporters showed a deviating pattern. It was also interesting to note that almost all model drugs could be grouped into the same biopharmaceutics classification system as that classified by the human intestinal permeability when the P app was plotted as a function of dose number (D 0 ) of each drug.

International journal of pharmaceutics, Jan 10, 2014

We have previously reported that the limited intestinal absorption via the paracellular pathway m... more We have previously reported that the limited intestinal absorption via the paracellular pathway may be the primary cause of the low oral bioavailability of doxorubicin (DOX). In this study, we have formulated medium chain glycerides-based colloidal nanosystems to enhance the intestinal paracellular absorption of DOX and reduce its cardiotoxicity. The DOX formulations prepared by the construction of pseudo-ternary phase diagram were characterized in terms of their droplet size distribution, viscosity, drug loading, and drug release. Further evaluation was conducted by an in vitro Caco-2 transport study as well as in situ/in vivo intestinal absorption, bioavailability and toxicity studies. Compared with DOX solution, these formulations enhanced the absorptive transport of DOX across Caco-2 cell monolayers at least partly due to the paracellular-enhancing effects of their lipidic components. Moreover, the in situ intestinal absorption and in vivo oral bioavailability of DOX in rats wer...

International journal of pharmaceutics, Jan 15, 2011

Biocompatible microparticles prepared by lyophilization were developed for intranasal protein del... more Biocompatible microparticles prepared by lyophilization were developed for intranasal protein delivery. To test for the feasibility of this formulation, stability of the incorporated protein and enhancement of in vitro permeation across the nasal epithelium were evaluated. Lyophilization was processed with hydroxypropylmethylcellulose (HPMC) or water soluble chitosan (WCS) as biocompatible polymers, hydroxypropyl-β-cyclodextrin (HP-β-CD) and d-alpha-tocopheryl poly(ethylene glycol 1000) succinate (TPGS 1000) as permeation enhancers, sugars as cryoprotectants and lysozyme as the model protein. As a result, microparticles ranging from 6 to 12μm were developed where the maintenance of the protein conformation was verified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), circular dichroism and fluorescence intensity detection. Moreover, in vitro bioassay showed that the lysozyme activity was preserved during the preparation process while exhibiting less cytotoxic...

International journal of pharmaceutics, Jan 15, 2010

The aim of this study was to prepare microparticles (MPs) of granisetron (GRN) in combination wit... more The aim of this study was to prepare microparticles (MPs) of granisetron (GRN) in combination with hydroxypropyl-β-cyclodextrin (HP-β-CD) and sodium carboxymethylcellulose (CMC-Na) by the simple freeze-drying method for intranasal delivery. The composition of MPs was determined from the phase-solubility study of GRN in various CDs. Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD) analysis and differential scanning calorimetry (DSC) studies were performed to evaluate possible interactions between GRN and excipients. The results indicated the formation of inclusion complex between GRN and CD, and the conversion of drug into amorphous state. The in vitro release of GRN from MPs was determined in phosphate buffered saline (pH 6.4) at 37°C. Cytotoxicity of the MPs and in vitro permeation study were conducted by using primary human nasal epithelial (HNE) cells and their monolayer system cultured by air-liquid interface (ALI) method, respectively. The MPs sh...

International journal of pharmaceutics, Jan 29, 2007

An improved PEGylated liposomal formulation of paclitaxel has been developed with the purpose of ... more An improved PEGylated liposomal formulation of paclitaxel has been developed with the purpose of improving the solubility of paclitaxel as well as the physicochemical stability of liposome in comparison to the current Taxol formulation. The use of 3% (v/v) Tween 80 in the hydration media was able to increase the solubility of drug. The addition of sucrose as a lyoprotectant in the freeze-drying process increased the stability of the liposome particles. There was no significant difference in the entrapment efficiency of paclitaxel between the conventional non-PEGylated liposomes and our PEGylated liposomes. Cytotoxicity in human breast cancer cell lines (MDA-MB-231 and SK-BR-3) of our paclitaxel formulation was less potent compared to Taxol after 24h incubation, but was equipotent after 72 h due to the slower release of drug from the liposome. Our PEGylated liposomes increased the biological half-life of paclitaxel from 5.05 (+/-1.52)h to 17.8 (+/-2.35)h compared to the conventional ...

Pharmaceutical research, 2003

To evaluate the feasibility of using a serially passaged culture of human nasal epithelial cell m... more To evaluate the feasibility of using a serially passaged culture of human nasal epithelial cell monolayers on a permeable support for in vitro drug transport studies. The optimum conditions for passaged culture as well as the correlation between the transepithelial electrical resistance (TEER) value and drug permeability (Papp) were evaluated. Fresh human nasal epithelial cells were collected from normal inferior turbinates and were subcultured repeatedly in serum-free bronchial epithelial cell growth media (BEGM) in petri dishes. The subcultured cells of each passage were seeded onto permeable supports at 5 x 10(5) cells/cm2 and grown in Dulbecco's modified Eagle medium (DMEM). Morphologic characteristics were observed by scanning electron microscopy (SEM). To verify the formation of tight junctions, actin staining and transmission electron microscopy (TEM) studies were conducted. In the drug transport study, [14C]mannitol and budesonide were selected as the paracellular and th...

International journal of pharmaceutics, Jan 15, 2000

The effect of various pore formers on the controlled release of an antibacterial agent from a pol... more The effect of various pore formers on the controlled release of an antibacterial agent from a polymeric device was examined in order to develop a novel biomaterial that prevents bacterial adhesion and growth on its surface. Cefadroxil was chosen as the model antibiotic and was incorporated into a polyurethane matrix by the solvent-casting method. Polyethylene glycol (PEG) 1450, D-mannitol, or bovine serum albumin (BSA) was used as a pore former. The amount of cefadroxil released from various formulations at 37 degrees C was measured by HPLC. The morphological change of matrices before and after release studies was investigated by scanning electron microscopy (SEM). The duration of antimicrobial activities of matrices against Escherichia coli and Bacillus subtilis was evaluated by measuring the diameters of the inhibition zone. Changing the weight fraction and particle size of the pore formers/drug mixtures could control the release of cefadroxil from the matrix. The release rate of ...

International journal of pharmaceutics, Jan 5, 2009

To enhance the solubility and bioavailability of poorly water-soluble Coenzyme Q(10) (CoQ(10)), s... more To enhance the solubility and bioavailability of poorly water-soluble Coenzyme Q(10) (CoQ(10)), self-emulsifying drug delivery system (SEDDS) composed of oil, surfactant and cosurfactant for oral administration of CoQ(10) was formulated. The solubility of CoQ(10) was determined in various oils and surfactants. The formulations were prepared using two oils (Labrafil M 1944 and Labrafil M 2125), surfactant (Labrasol) and cosurfactant (Lauroglycol FCC and Capryol 90). In all the formulations, the level of CoQ(10) was fixed at 6% (w/v) of the vehicle. These formulations were characterized by solubility of the drug in the vehicle, particle size of the dispersed emulsion, zeta potential and drug release profile. Ternary phase diagrams were used to evaluate the emulsification domain. The self-emulsification time following introduction into an aqueous medium under gentle agitation was evaluated. The optimized SEDDS formulation consist of 65% (v/v) Labrasol, 25% (v/v) Labrafil M 1944 CS and ...

International journal of pharmaceutics, Jan 14, 2011

A Shirasu-porous-glass (SPG) membrane with a mean pore size of 2.5 μm was used to produce an oil/... more A Shirasu-porous-glass (SPG) membrane with a mean pore size of 2.5 μm was used to produce an oil/water (O/W) nanoemulsion of flurbiprofen consisting of methylene chloride as the dispersed phase, polyvinyl alcohol (PVA) as the stabilizer and a mixture of Tween 20 and Tween 80 in demineralized water as the continuous phase. Emulsion droplets with a mean droplet size of 25 times smaller than the mean pore size and a narrow droplet size distribution were produced using 5% emulsifier at a feed pressure of 15 kPa. Under these conditions the z-average diameter and size distribution of the emulsion droplets formed were influenced by the type of surfactant, agitator speed (150-1200 rpm), feed pressure (15-80 kPa), stabilizer concentration (0-4, w/v) and the temperature of the continuous phase. Increasing the agitator speed and stabilizer concentration increased the z-average diameter and decreased the size uniformity. There was a linear relationship between the increased feed pressure and th...

International journal of pharmaceutics, Jan 2, 2010

To enhance the solubility and bioavailability of poorly absorbable fexofenadine, microemulsion sy... more To enhance the solubility and bioavailability of poorly absorbable fexofenadine, microemulsion system composed of oil, surfactant and co-surfactant was developed for intranasal delivery. Phase behavior, particle size, viscosity and solubilization capacity of the microemulsion system were characterized. Histopathology and in vivo nasal absorption of the optimized microemulsion formulations were also investigated in rats. A single isotropic region was found in the pseudo-ternary phase diagrams developed at various ratios with Lauroglycol 90 as oil, Labrasol as surfactant and Plurol oleiqueCC49 or its mixture with PEG-400 (1:1) as cosurfactant. An increase in the microemulsion region in pseudo-ternary phase systems was observed with increased surfactant concentration. The optimized microemulsion formulations showed higher solubulization of fexofenadine, i.e., F1 (22.64mg/mL) and F2 (22.98mg/mL), compared to its intrinsic water solubility (1.51mg/mL). Nasal absorption of fexofenadine fr...

International Journal of Pharmaceutics, 2001

1-(4-Methylpiperazinyl)-3-phenylisoquinoline hydrochloride (CWJ-a-5) is a newly developed from be... more 1-(4-Methylpiperazinyl)-3-phenylisoquinoline hydrochloride (CWJ-a-5) is a newly developed from benzo[c]phenanthridine alkaloids and derivative and has exhibited potent antitumor activities, in vitro and in vivo. The pharmacokinetics of this novel antitumor 3-arylisoquinoline derivative was studied after intravenous (i.v.), oral (p.o.) and hepatoportal (p.v.) administration in rats. A simple high performance liquid chromatographic method was developed to determine the concentrations of CWJ-a-5 in plasma, bile and urine. Plasma concentration profiles of CWJ-a-5 were best fitted by the two-compartment model after i.v. administration and showed a linear pharmacokinetic behavior up to 20 mg/kg doses. The half-life of CWJ-a-5 in the post-distributive phase (t1/2beta), total-body plasma clearance (CLt), and volume of distribution at steady-state (Vdss) were 86.9 min, 5.72 l/h per kilogram and 9.79 l/kg, respectively, after i.v. administration of 10 mg/kg. Biliary and urinary excretion of CWJ-a-5 was &lt; 1% after i.v. injection of 10 mg/kg. The bioavailability of CWJ-a-5 after p.o. and p.v. administration (50 and 10 mg/kg, respectively) was 52.9 and 72.2%, respectively. Gastrointestinal bioavailability was calculated to be 73.3%. The apparent partition coefficient (log P) of CWJ-a-5 between n-octanol and water was 2.64. Plasma protein binding of CWJ-a-5 measured by the ultrafiltration method was &gt; 95%.

PloS one, 2014

In many studies for chemoembolization of hepatocellular carcinoma, the Lipiodol emulsion preparat... more In many studies for chemoembolization of hepatocellular carcinoma, the Lipiodol emulsion preparation protocols, especially the mixing steps, were unclear or even unrevealed at all. However, doxorubicin (DOX) release may depend on the composition and volume ratio (Lipiodol to DOX solution) of a Lipiodol emulsion. Therefore, we conducted a preclinical study to compare in-vitro drug release and in-vivo pharmacokinetics of DOX from diverse Lipiodol emulsions and drug-eluting beads (DEBs) and to compare the tumor response in a rabbit VX2 carcinoma model. DOX release profiles of four types of Lipiodol emulsions with different media (normal saline or Pamiray as an iodinated contrast medium), volume ratio (Lipiodol to DOX solution), and DEBs were investigated in-vitro. For the in-vivo study, 15 rabbits bearing VX2 carcinoma in the liver were treated with 4∶1 volume ratio Lipiodol emulsion (group A), 1∶1 volume ratio Lipiodol emulsion (group B), and DEBs (group C) chemoembolization. Blood an...

Journal of Pharmaceutical Investigation, 2012

Spray-dried microspheres based on polysaccharides were developed and the conformational stability... more Spray-dried microspheres based on polysaccharides were developed and the conformational stability and controlled release of incorporated protein were evaluated using bovine serum albumin (BSA) as a model protein. Microspheres composed of water soluble chitosan (WCS), hydroxypropyl-b-cyclodextrin (HP-b-CD) and polyethylene glycol (PEG) were prepared by spray dying. WCS was used as a mucoadhesive and biocompatible polymer. HP-b-CD and PEG were used as protein stabilizer during the spray drying process. Microspheres with 6-7 lm of mean diameter were successfully developed. Encapsulation efficiency of BSA in microsphere was over 70 %. Primary, secondary and tertiary structure of incorporated BSA in microsphere was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, circular dichroism, and fluorescence intensity measurement, respectively. Conformational stability of BSA was maintained during the spray drying process. BSA release from microspheres was evaluated in in vitro model using the Transwell Ò insert, and showed a sustained release profile compared to naive BSA. Thus, these microspheres could possibly serve as an optimized delivery system for preserved stability and sustained release of protein.

Journal of Pharmaceutical Investigation, 2013

The prevalence of obesity has soared in recent decades, and now is considered as a worldwide prob... more The prevalence of obesity has soared in recent decades, and now is considered as a worldwide problem, with significant health and medical implications. Obesity is often linked to several co-morbidities including diabetes, cardiovascular diseases, and cancers, and a number of drugs are available for the treatment of these diseases. Moreover, obesity can affect various physiological factors including plasma proteins, drug metabolizing enzymes, drug transporters, and blood flow, thereby altering drug absorption, distribution, metabolism, and excretion (ADME). Therefore, information regarding obesity-related physiological changes and their pharmacokinetic consequences is crucial for understanding pharmacokinetics and optimizing drug therapy in obese population. Herein, this article reviews the effects of obesity on physiological factors determining drug ADME and their pharmacokinetic consequences. In addition, a brief summary on animal models of obesity is presented.

Studies in Mechanobiology, Tissue Engineering and Biomaterials, 2010

Reconstitution of the articular cartilage tissue can be achieved by cell delivery techniques. How... more Reconstitution of the articular cartilage tissue can be achieved by cell delivery techniques. However, an optimal procedure exhibiting minimal toxicity and maximum therapeutic efficacy is still to be developed. The two most common cell types that are being investigated for the treatment of osteoarthritis are chondrocytes and mesenchymal stem cells which need to be formulated with the proper signaling molecules

Biotechnology: Pharmaceutical Aspects, 2008

An improved PEGylated liposomal formulation of paclitaxel has been developed with the purpose of ... more An improved PEGylated liposomal formulation of paclitaxel has been developed with the purpose of improving the solubility of paclitaxel as well as the physicochemical stability of liposome in comparison to the current Taxol® formulation. The use of 3% (v/v) Tween 80 in the hydration media was able to increase the solubility of drug. The addition of sucrose as a lyoprotectant

PLOS ONE, 2015

Oral solid formulations based on Angelica gigas Nakai (AGN) and Soluplus were prepared by the hot... more Oral solid formulations based on Angelica gigas Nakai (AGN) and Soluplus were prepared by the hot-melting extrusion (HME) method. AGN was pulverized into coarse and ultrafine particles, and their particle size and morphology were investigated. Ultrafine AGN particles were used in the HME process with high shear to produce AGN-based formulations. In simulated gastrointestinal fluids (pH 1.2 and pH 6.8) and water, significantly higher amounts of the major active components of AGN, decursin (D) and decursinol angelate (DA), were extracted from the HME-processed AGN/Soluplus (F8) group than the AGN EtOH extract (ext) group (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). Based on an in vivo pharmacokinetic study in rats, the relative oral bioavailability of decursinol (DOH), a hepatic metabolite of D and DA, in F8-administered mice was 8.75-fold higher than in AGN EtOH ext-treated group. In scopolamine-induced memory-impaired mice, F8 exhibited a more potent cognitive enhancing effect than AGN EtOH ext in both a Morris water maze test and a passive avoidance test. These findings suggest that HME-processed AGN/Soluplus formulation (F8) could be a promising therapeutic candidate for memory impairment.

Biopharmaceutics & drug disposition, Jan 21, 2015

The pharmacokinetics of lobeglitazone (LB) was studied after intravenous administration of a dose... more The pharmacokinetics of lobeglitazone (LB) was studied after intravenous administration of a dose at 1 mg/kg and oral administration of doses at 0.1, 1 and 10 mg/kg in male and female rats. The area under the plasma concentration-time curve from time zero to infinity (AUCinf ) after intravenous administration was approximately 7.1 times higher in female rats than in male rats. In addition, the AUCinf in the case of oral administration was at least 4.4 times higher in female rats and appeared to increase in proportion to the dose in both genders. The in vitro half-lives were 18.8 ± 4.45 min and 60.7 ± 11.2 min, as evidenced by incubating liver microsomes obtained from male and female rats, respectively. As a result, the estimated CLint for LB for male rat liver microsomes (0.0779 ± 0.0233 mL/min/mg protein) was much higher than that for female rat liver microsomes (0.0233 ± 0.0039 mL/min/mg protein, p < 0.05). These observations suggest that there are gender differences in the pha...

International journal of pharmaceutics, Jan 18, 2015

Poly(d,l-lactic acid)-glycerol (PDLLA-G)-based nanoparticles (NPs) were fabricated for the intrav... more Poly(d,l-lactic acid)-glycerol (PDLLA-G)-based nanoparticles (NPs) were fabricated for the intravenous delivery of curcumin (CUR). NPs with a mean diameter of approximately 200nm, a narrow size distribution, and capable of efficient drug encapsulation were prepared using an emulsification-solvent evaporation method. The stability of NPs was verified in water, phosphate buffered saline (PBS), and serum after 24-h incubation. A sustained drug release pattern was observed, and the amount of CUR released in acidic media (pH 5.5) was higher than in media at physiological pH (pH 7.4). Blank NPs (without drug loading) did not exhibit severe cytotoxicity in MDA-MB-231 human breast adenocarcinoma cells. The in vitro anti-tumor efficacy of CUR-loaded NPs in MDA-MB-231 cells was comparable to that of a solution of CUR. Pharmacokinetic studies in rats showed that the in vivo clearance (CL) of CUR in the NP-treated group was lower than the group treated with CUR solution. Therefore, encapsulatio...

Journal of Pharmaceutical Investigation, 2012

Transport studies of model drugs were conducted across the human nasal epithelial (HNE) and norma... more Transport studies of model drugs were conducted across the human nasal epithelial (HNE) and normal human bronchial epithelial (NHBE) cell monolayers cultured by air-liquid interface method. Physicochemical properties (e.g., molecular weight, calculated partition coefficient, dose number) of model drugs were quoted from literatures and apparent permeability coefficients (P app ) across the HNE and NHBE cell monolayers were directly measured. A linear relationship was observed between the P app values of model drugs in the HNE and NHBE cell monolayers. As the molecular weight of model drugs increased, the P app showed a decreasing pattern while the increase of partition coefficients resulted in the increment of P app . These results indicated that the transport of model drugs across both cell monolayers followed mainly the passive diffusion mechanism, although substrates mediated by drug transporters showed a deviating pattern. It was also interesting to note that almost all model drugs could be grouped into the same biopharmaceutics classification system as that classified by the human intestinal permeability when the P app was plotted as a function of dose number (D 0 ) of each drug.

International journal of pharmaceutics, Jan 10, 2014

We have previously reported that the limited intestinal absorption via the paracellular pathway m... more We have previously reported that the limited intestinal absorption via the paracellular pathway may be the primary cause of the low oral bioavailability of doxorubicin (DOX). In this study, we have formulated medium chain glycerides-based colloidal nanosystems to enhance the intestinal paracellular absorption of DOX and reduce its cardiotoxicity. The DOX formulations prepared by the construction of pseudo-ternary phase diagram were characterized in terms of their droplet size distribution, viscosity, drug loading, and drug release. Further evaluation was conducted by an in vitro Caco-2 transport study as well as in situ/in vivo intestinal absorption, bioavailability and toxicity studies. Compared with DOX solution, these formulations enhanced the absorptive transport of DOX across Caco-2 cell monolayers at least partly due to the paracellular-enhancing effects of their lipidic components. Moreover, the in situ intestinal absorption and in vivo oral bioavailability of DOX in rats wer...

International journal of pharmaceutics, Jan 15, 2011

Biocompatible microparticles prepared by lyophilization were developed for intranasal protein del... more Biocompatible microparticles prepared by lyophilization were developed for intranasal protein delivery. To test for the feasibility of this formulation, stability of the incorporated protein and enhancement of in vitro permeation across the nasal epithelium were evaluated. Lyophilization was processed with hydroxypropylmethylcellulose (HPMC) or water soluble chitosan (WCS) as biocompatible polymers, hydroxypropyl-β-cyclodextrin (HP-β-CD) and d-alpha-tocopheryl poly(ethylene glycol 1000) succinate (TPGS 1000) as permeation enhancers, sugars as cryoprotectants and lysozyme as the model protein. As a result, microparticles ranging from 6 to 12μm were developed where the maintenance of the protein conformation was verified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), circular dichroism and fluorescence intensity detection. Moreover, in vitro bioassay showed that the lysozyme activity was preserved during the preparation process while exhibiting less cytotoxic...

International journal of pharmaceutics, Jan 15, 2010

The aim of this study was to prepare microparticles (MPs) of granisetron (GRN) in combination wit... more The aim of this study was to prepare microparticles (MPs) of granisetron (GRN) in combination with hydroxypropyl-β-cyclodextrin (HP-β-CD) and sodium carboxymethylcellulose (CMC-Na) by the simple freeze-drying method for intranasal delivery. The composition of MPs was determined from the phase-solubility study of GRN in various CDs. Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD) analysis and differential scanning calorimetry (DSC) studies were performed to evaluate possible interactions between GRN and excipients. The results indicated the formation of inclusion complex between GRN and CD, and the conversion of drug into amorphous state. The in vitro release of GRN from MPs was determined in phosphate buffered saline (pH 6.4) at 37°C. Cytotoxicity of the MPs and in vitro permeation study were conducted by using primary human nasal epithelial (HNE) cells and their monolayer system cultured by air-liquid interface (ALI) method, respectively. The MPs sh...

International journal of pharmaceutics, Jan 29, 2007

An improved PEGylated liposomal formulation of paclitaxel has been developed with the purpose of ... more An improved PEGylated liposomal formulation of paclitaxel has been developed with the purpose of improving the solubility of paclitaxel as well as the physicochemical stability of liposome in comparison to the current Taxol formulation. The use of 3% (v/v) Tween 80 in the hydration media was able to increase the solubility of drug. The addition of sucrose as a lyoprotectant in the freeze-drying process increased the stability of the liposome particles. There was no significant difference in the entrapment efficiency of paclitaxel between the conventional non-PEGylated liposomes and our PEGylated liposomes. Cytotoxicity in human breast cancer cell lines (MDA-MB-231 and SK-BR-3) of our paclitaxel formulation was less potent compared to Taxol after 24h incubation, but was equipotent after 72 h due to the slower release of drug from the liposome. Our PEGylated liposomes increased the biological half-life of paclitaxel from 5.05 (+/-1.52)h to 17.8 (+/-2.35)h compared to the conventional ...

Pharmaceutical research, 2003

To evaluate the feasibility of using a serially passaged culture of human nasal epithelial cell m... more To evaluate the feasibility of using a serially passaged culture of human nasal epithelial cell monolayers on a permeable support for in vitro drug transport studies. The optimum conditions for passaged culture as well as the correlation between the transepithelial electrical resistance (TEER) value and drug permeability (Papp) were evaluated. Fresh human nasal epithelial cells were collected from normal inferior turbinates and were subcultured repeatedly in serum-free bronchial epithelial cell growth media (BEGM) in petri dishes. The subcultured cells of each passage were seeded onto permeable supports at 5 x 10(5) cells/cm2 and grown in Dulbecco's modified Eagle medium (DMEM). Morphologic characteristics were observed by scanning electron microscopy (SEM). To verify the formation of tight junctions, actin staining and transmission electron microscopy (TEM) studies were conducted. In the drug transport study, [14C]mannitol and budesonide were selected as the paracellular and th...

International journal of pharmaceutics, Jan 15, 2000

The effect of various pore formers on the controlled release of an antibacterial agent from a pol... more The effect of various pore formers on the controlled release of an antibacterial agent from a polymeric device was examined in order to develop a novel biomaterial that prevents bacterial adhesion and growth on its surface. Cefadroxil was chosen as the model antibiotic and was incorporated into a polyurethane matrix by the solvent-casting method. Polyethylene glycol (PEG) 1450, D-mannitol, or bovine serum albumin (BSA) was used as a pore former. The amount of cefadroxil released from various formulations at 37 degrees C was measured by HPLC. The morphological change of matrices before and after release studies was investigated by scanning electron microscopy (SEM). The duration of antimicrobial activities of matrices against Escherichia coli and Bacillus subtilis was evaluated by measuring the diameters of the inhibition zone. Changing the weight fraction and particle size of the pore formers/drug mixtures could control the release of cefadroxil from the matrix. The release rate of ...

International journal of pharmaceutics, Jan 5, 2009

To enhance the solubility and bioavailability of poorly water-soluble Coenzyme Q(10) (CoQ(10)), s... more To enhance the solubility and bioavailability of poorly water-soluble Coenzyme Q(10) (CoQ(10)), self-emulsifying drug delivery system (SEDDS) composed of oil, surfactant and cosurfactant for oral administration of CoQ(10) was formulated. The solubility of CoQ(10) was determined in various oils and surfactants. The formulations were prepared using two oils (Labrafil M 1944 and Labrafil M 2125), surfactant (Labrasol) and cosurfactant (Lauroglycol FCC and Capryol 90). In all the formulations, the level of CoQ(10) was fixed at 6% (w/v) of the vehicle. These formulations were characterized by solubility of the drug in the vehicle, particle size of the dispersed emulsion, zeta potential and drug release profile. Ternary phase diagrams were used to evaluate the emulsification domain. The self-emulsification time following introduction into an aqueous medium under gentle agitation was evaluated. The optimized SEDDS formulation consist of 65% (v/v) Labrasol, 25% (v/v) Labrafil M 1944 CS and ...

International journal of pharmaceutics, Jan 14, 2011

A Shirasu-porous-glass (SPG) membrane with a mean pore size of 2.5 μm was used to produce an oil/... more A Shirasu-porous-glass (SPG) membrane with a mean pore size of 2.5 μm was used to produce an oil/water (O/W) nanoemulsion of flurbiprofen consisting of methylene chloride as the dispersed phase, polyvinyl alcohol (PVA) as the stabilizer and a mixture of Tween 20 and Tween 80 in demineralized water as the continuous phase. Emulsion droplets with a mean droplet size of 25 times smaller than the mean pore size and a narrow droplet size distribution were produced using 5% emulsifier at a feed pressure of 15 kPa. Under these conditions the z-average diameter and size distribution of the emulsion droplets formed were influenced by the type of surfactant, agitator speed (150-1200 rpm), feed pressure (15-80 kPa), stabilizer concentration (0-4, w/v) and the temperature of the continuous phase. Increasing the agitator speed and stabilizer concentration increased the z-average diameter and decreased the size uniformity. There was a linear relationship between the increased feed pressure and th...

International journal of pharmaceutics, Jan 2, 2010

To enhance the solubility and bioavailability of poorly absorbable fexofenadine, microemulsion sy... more To enhance the solubility and bioavailability of poorly absorbable fexofenadine, microemulsion system composed of oil, surfactant and co-surfactant was developed for intranasal delivery. Phase behavior, particle size, viscosity and solubilization capacity of the microemulsion system were characterized. Histopathology and in vivo nasal absorption of the optimized microemulsion formulations were also investigated in rats. A single isotropic region was found in the pseudo-ternary phase diagrams developed at various ratios with Lauroglycol 90 as oil, Labrasol as surfactant and Plurol oleiqueCC49 or its mixture with PEG-400 (1:1) as cosurfactant. An increase in the microemulsion region in pseudo-ternary phase systems was observed with increased surfactant concentration. The optimized microemulsion formulations showed higher solubulization of fexofenadine, i.e., F1 (22.64mg/mL) and F2 (22.98mg/mL), compared to its intrinsic water solubility (1.51mg/mL). Nasal absorption of fexofenadine fr...

International Journal of Pharmaceutics, 2001

1-(4-Methylpiperazinyl)-3-phenylisoquinoline hydrochloride (CWJ-a-5) is a newly developed from be... more 1-(4-Methylpiperazinyl)-3-phenylisoquinoline hydrochloride (CWJ-a-5) is a newly developed from benzo[c]phenanthridine alkaloids and derivative and has exhibited potent antitumor activities, in vitro and in vivo. The pharmacokinetics of this novel antitumor 3-arylisoquinoline derivative was studied after intravenous (i.v.), oral (p.o.) and hepatoportal (p.v.) administration in rats. A simple high performance liquid chromatographic method was developed to determine the concentrations of CWJ-a-5 in plasma, bile and urine. Plasma concentration profiles of CWJ-a-5 were best fitted by the two-compartment model after i.v. administration and showed a linear pharmacokinetic behavior up to 20 mg/kg doses. The half-life of CWJ-a-5 in the post-distributive phase (t1/2beta), total-body plasma clearance (CLt), and volume of distribution at steady-state (Vdss) were 86.9 min, 5.72 l/h per kilogram and 9.79 l/kg, respectively, after i.v. administration of 10 mg/kg. Biliary and urinary excretion of CWJ-a-5 was &lt; 1% after i.v. injection of 10 mg/kg. The bioavailability of CWJ-a-5 after p.o. and p.v. administration (50 and 10 mg/kg, respectively) was 52.9 and 72.2%, respectively. Gastrointestinal bioavailability was calculated to be 73.3%. The apparent partition coefficient (log P) of CWJ-a-5 between n-octanol and water was 2.64. Plasma protein binding of CWJ-a-5 measured by the ultrafiltration method was &gt; 95%.

PloS one, 2014

In many studies for chemoembolization of hepatocellular carcinoma, the Lipiodol emulsion preparat... more In many studies for chemoembolization of hepatocellular carcinoma, the Lipiodol emulsion preparation protocols, especially the mixing steps, were unclear or even unrevealed at all. However, doxorubicin (DOX) release may depend on the composition and volume ratio (Lipiodol to DOX solution) of a Lipiodol emulsion. Therefore, we conducted a preclinical study to compare in-vitro drug release and in-vivo pharmacokinetics of DOX from diverse Lipiodol emulsions and drug-eluting beads (DEBs) and to compare the tumor response in a rabbit VX2 carcinoma model. DOX release profiles of four types of Lipiodol emulsions with different media (normal saline or Pamiray as an iodinated contrast medium), volume ratio (Lipiodol to DOX solution), and DEBs were investigated in-vitro. For the in-vivo study, 15 rabbits bearing VX2 carcinoma in the liver were treated with 4∶1 volume ratio Lipiodol emulsion (group A), 1∶1 volume ratio Lipiodol emulsion (group B), and DEBs (group C) chemoembolization. Blood an...