• Polymer(Korea)
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• v.38 no.1
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• pp.43-48
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• 2014

In this paper, we made a new polycationic polymeric liposome composed of low molecular weight polyethylenimine (PEI) and 10,12-pentacosadiynoic acid (PCDA). PCDA liposome was prepared by ultraviolet irradiation. PEI was further conjugated on the surface of the polymerized PCDA liposome using coupling reagents to make PCDA-PEI. The blue-to-red transition of PCDA liposome was observed during the coupling reaction. The size distribution of liposome and complexes with plasmid DNA was measured by dynamic light scattering (DLS). The complex formation was also identified by agarose gel electrophoresis and PicoGreen reagent assay. We confirmed the complex formation of the polymeric liposome with DNA and then performed transfection and cytotoxicity assay in HEK 293 and HeLa cells. As a result, PCDA-PEI showed significant gene transfection efficiency and low cytotoxicity. This study shows that PEI-conjugated PCDA liposome could be an efficient gene or drug delivery carrier.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.5 no.2
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• pp.89-100
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• 2019

In our previous studies, we developed a ¹⁸F-labeled TSPO-binding ligand, named [¹⁸F]CB251, which has been proved to be a promising TSPO-binding PET radiotracer for the detection and monitoring of TSPO expression in pathological diseases. (Ki = 0.27 nM for TSPO, 1.96% ID/g of tumor uptake at 1h post-injection) Based on these results, we utilized 6,8-dichloro-2-phenylimidazo[1,2-a]pyridineacetamide analogs, CB185 (1) as a targeting moiety for the selective delivery of probes and anticancer molecules to TSPO-overexpressed tissues. In this study, we designed CB185 derivatives contains different PEG chains (n = 1, 3 and 5) and fluorescence dye (Cy5) to identify the necessary space between a TSPO-binding ligand and an anticancer agent. Three CB185 derivatives (11a-c) which contains Cy5 and PEG chain, were synthesized and the effect of PEG additive on their TSPO-binding affinities were evaluated using in vitro assays. The binding affinity for compounds 11a-c was lower than that of PK11195 (Ki = 3.2 nM), but still characterized by nanomolar binding affinity for TSPO (Ki = 46.5 nM for 11a, 51.0 nM for 11b, and 388.5 nM for 11c). These results showed that the conjugates are characterized by a moderate binding affinity toward TSPO except for compound 11c, which PEG chain consist of five PEG monomers. Our finding might add useful information to decide the appropriate PET chain length for developing new TSPO-targeting drug carriers.

• Korean Chemical Engineering Research
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• v.47 no.4
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• pp.453-458
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• 2009

Recently, new methods to synthesize and process polymers without toxic organic solvents are needed in order to solve environmental problems. The use of supercritical carbon dioxide as a solvent for the polymer synthesis is attractive since it is non-toxic, non-flammable, naturally abundant, and the product may be easily separated from the solvent. In this study, we developed the method using super critical $CO_2$ to prepare P(MAA-co-EGMA) hydrogel nanoparticles as an intelligent drug delivery carrier. The effects of concentrations of PtBuMA-PEO as a dispersion stabilizer and AIBN as an initiator on the particle synthesis were investigated. When PtBuMA-PEO concentration increased, the particle size decreased. However, there was no significant difference in the particle size according to the AIBN concentration. There was a drastic change of the equilibrium weight swelling ratio of P(MAA-co-EGMA) hydrogel nanoparticles at a pH of around 5, which is the $pK_a$ of PMAA. At a pH below 5, the hydrogels were in a relatively collapsed state but at a pH higher than 5, the hydrogels swelled to a high degree. In release experiments using Rh-B as a model solute, the P(MAA-co-EGMA) hydrogel nanoparticles showed a pH-sensitive release behavior. At low pH(pH 4.0) a small amount of Rh-B was released while at high pH(pH 6.0) a relatively large amount of Rh-B was released from the hydrogels.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.46 no.2
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• pp.133-145
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• 2020

This study utilized nano-liposomes for the purpose of stabilizing and increasing the solubility of biotin, a water-soluble active material with low solubility. The particle size, zeta potential, and polydispersity index were confirmed with a nano zetasizer. It was possible to manufacture nano liposomes at 100 to 250 nm of particle size and -80 to -30 mV of zeta potential. Dialysis membrane method (DMM) was used to measure the capsulation efficiency of biotin in biotin nano-liposomes, and results showed that pH increased biotin nano-liposomes had higher capsulation efficiency than normal biotin nano-liposome. Through this experiment, it was confirmed that the pH has a great influence on the stability of biotin nano-liposomes. In vitro franz diffusion cell method was used to measure in vitro skin absorption rate of biotin nano-liposomes. The shape of the formulation and biotin solubility in nano-liposome was observed by cryogenic transmission electron microscopy (cryo-TEM). Through this study, we confirmed that biotin, which is introduced as closely related to hair health, can be incorporated into a nano-liposome drug delivery system, to make biotin nano-liposome with improved solubility and precipitation problems.

• Journal of the Korean Chemical Society
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• v.60 no.3
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• pp.187-193
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• 2016

In this study, preparation of positively and negatively charged carbon nanotube (CNT)-collagen (CG) hydrogels with pH sensitive characteristic was reported. The positive and negative characteristics of the prepared hydrogels were created by introduction of positively functionalized CNT-NH₂ and negatively functionalized CNT-COOH, respectively, into the collagen hydrogel. The surface charge of CNTs (CNT-NH₂ and CNT-COOH), CG and CNTs/CG hydrogels was measured by Zetasizer. The swelling ratios of CNT-NH₂/CG and CNT-COOH/CG hydrogels in aqueous solution were checked by measuring of weight changes of the hydrogels in the range of pH 2~10. In detail, the positively charged CNT-NH₂/CG hydrogel swelled up to 5% at pH 4 in comparison to the weight at pH 7, while the negatively charged CNT-COOH/CG hydrogel swelled up to 10% at pH 10. The prepared CNT-NH₂/CG and CNT-COOH/CG hydrogels will be very useful as pH sensitive oral drug-delivering systems for gastrointestine (pH ~2) and small intestine (pH ~9), respectively.

• Polymer(Korea)
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• v.28 no.1
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• pp.10-17
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• 2004

Poly(vinyl acetate) (PVAc) nanoparticles were synthesized in oil/water miniemulsion polymerization in the presence of low amount of hexadecane as a cosurfactant. The nanoparticles were tested to apply as a drug carrier. The shape of nanoparticles was observed by scanning electron microscopy, and the average particle size and size distribution were examined by particle size analyzer. Inclusion of antibiotic drugs into the nanoparticles was confirmed by CHO, C=O, and OH peak of FT-IR. Size of the nanoparticles were adjusted between 80∼300 nm by changing the homogenization rate and amount of cosurfactant and surfactant. The monomer droplets prepared by miniemulsion method using a cosurfactant were homogeneous and stable compared with those prepared by conventional emulsion polymerization. This might be occurred due to the prevention of Ostwald ripening and coalescence between droplets by using hexadecane as a cosurfactant.

• Biomolecules & Therapeutics
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• v.5 no.2
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• pp.125-132
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• 1997

Cisplatin, a platinum-complex, is currently one of the most effective compounds used in the treat-ment of solid tumors. However, its use is limited by severe side effects such as renal toxicity. Our platinum-based drug discovery program is aimed at developing drugs capable of diminishing toxicity and improving selective cytotoxicity. We synthesized new Pt (II) complex analogue containing 1,2-diaminocyclohexane (DACH) as carrier ligand and 1,2-bis (diphenylphosphino) ethane (DPPE) as a leaving group. Furthermore, nitrate was added to improve the solubility. A new series of [Pt(cia-DACH)(DPPE)] . $2NO_3$ (PC) was synthes-ized and characterized by their elemental analysis and by various spectroscopic techniques [infrared (IR), $_{13}$carbon nuclear magnetic resonance (NMR)] .PC demonstrated acceptable and significant antitumor activity against SKOV-3 and OVCAR-3 human ovarian carcinoma cell lines as compared with that of cisplatin. The cytotoxicity of PC in normal cells was found quite less than that of cisplatin using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), ($^3$H)thymidine uptake and glucose consumption tests in rabbit renal proximal tubular cells, human renal cortical cells and tissues. In conclusion, PC is considered to be more selective cytotoxicity toward human ovarian cancer cells than normal human/rabbit kidney cells.

• Journal of Pharmaceutical Investigation
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• v.41 no.4
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• pp.239-247
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• 2011

Simvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, an early and rate-limiting step in the biosynthesis of cholesterol. Simvastatin has good permeability, but it also has low solubility (BCS class II), which reduces its bioavailability. To overcome this problem, a solid dispersion is formed using a spray-dryer with polymeric material carrier to potentially enhance the dissolution rate and extend drug absorption. As carriers for solid dispersion, Gelucire$^{(R)}$44/14 and Gelucire$^{(R)}$ 50/13 are semisolid excipients that greatly improve the bioavailability of poorly-soluble drugs. To avoid any toxic effects of an organic solvent, we used aqueous medium to melt Tween$^{(R)}$ 80 and distilled water. The structural behaviors of the raw materials and the solid dispersion were analyzed by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). The DSC and PXRD data indicated that the crystalline structure of simvastatin was transformed to an amorphous structure through solid dispersion. Then, solid dispersion-based tablets containing 20 mg simvastatin were prepared with excipients. Dissolution tests were performed in distilled water and artificial intestinal fluid using the USP paddle II method. Compared with that of the commercial tablet (Zocor$^{(R)}$ 20 mg), the release of simvastatin from solid dispersion based-tablet was more efficient. Although the stability study is not complete, this solid dispersion system is expected to deliver poorly water-soluble drugs with enhanced bioavailability and less toxicity.

• Toxicological Research
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• v.17
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• pp.127-133
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• 2001

Together with cytochrome P450 (CYP), flavin-containing monooxygenase (FMO) present in liver microsomes oxidizes various endogenous and exogenous chemicals. In an effort to determine the human FMO activity, we have developed two non-invasive urine analysis methods using caffeine (CA) and ranitidine (RA) as the probe compounds. As the production of theobromine (TB) and ranitidine N-oxide (RANO) from CA and RA is catalyzed primarily by the hepatic FMO, we have assigned the urinary molar ratios of TB/CA and RA/RANO as the in vivo FMO activity. In 200 age-matched Korean volunteers, the obtained TB/CA ratio ranged from 0.4 to 15.2 (38-fold difference) and the RA/RANO ratio from 5.7 to 27.2 (4.8-fold). The FMO activity of 20's, determined by caffeine metabolism, was the highest (2.5$\pm$l.9) and those of 30's, 40's, 50's, 60's and 70's were 40%, 50%, 24%, 39% and 36% of the 20's, respectively. Intake of grapefruit juice, known to contain flavonoids, inhibited the in vivo FMO (TB/CA) activity by 79%. Addition of the flavonoids like naringin, quercitrin and kaempferol, present in grapefruit juice, to the in vitro microso-mal FMO assay, thiobenzamide S-oxidation, produced 75%, 70% and 60% inhibition, respectively. Obtained Ki values of quercitrin, kaempferol and naringin on the in vitro FMO activity were 6.2, 12.0 and 13.9 $\mu\textrm{M}$, respectively. This suggested that the dose of drug should need to be adjusted to suit the individual FMO activities when the drugs metabolized by FMO are given to patients. As the intake of grapefruit juice has been identified to inhibit the FMO as well as CYP3A4 and lA2 activities, patients taking drugs metabolized by these enzymes should not drink grapefruit juice as the carrier.

• Journal of Pharmaceutical Investigation
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• v.40 no.3
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• pp.139-153
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• 2010

Nitrosative stress is defined as pathophysiological conditions that are related to covalent modifications of proteins by nitration/nitrosylation by forms of nitrogen oxide ($NO_x$), leading to DNA damage, ultimately, cell death. This type of stress condition appears to be associated with a number of disease states, including diabetes, inflammation and neurodegenerative diseases. Since these pathological conditions are frequently chronic in nature and, thus, require long-term treatment, changes in pharmacokinetics are likely to affect the therapy. Transporters are membrane proteins that facilitate the movement of substrates, including drugs, across plasma membranes of epithelial / endothelial cells. Since it is now increasingly evident that transporters are pharmacokinetically significant, functional alteration of transporters by this stress condition may have therapeutic relevance. In this review, experimental techniques that are used to study both in vivo and in vitro nitrosative stress are summarized and discussed, along with available literature information on the functional implication of transporters under conditions of nitrosative stress conditions. In the literature, both functional induction and impa irment were apparently present for both drug transporter families [i.e., ATP-binding cassette (ABC) and solute carrier families (SLC)]. Furthermore, a change in the function of a certain transporter appears to have temporal dependency by impairment in the early phase of nitrosative stress and induction thereafter, suggesting that the role of nitrosative stress is complex in terms of functional implications of the transporters. Although the underlying mechanisms for these alterations are not fully understood, protein nitration/nitrosylation appears to be involved in the functional impairment whereas transcript factor(s) activated by nitrosative stress may play a role, at least in part, in functional induction. Interestingly, functional induction under conditions of nitrosative stress has not been observed for SLC transporters while such impairment has been documented for both ABC and SLC transporters. Further investigations appear to be necessary to fully delineate the underlying reasons for these differences on the impact and importance of nitrosative stress conditions.