Yu-Kyoung Oh

Seoul National University, Sŏul, Seoul, South Korea

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Publications (141)565.75 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Here, we report the non-covalent functionalization of reduced graphene oxide (rGO) nanosheets using chimeric peptides engineered to have a biologically functional sequence, a spacer sequence, and an rGO-binding sequence. As a model peptide with biological activity, the cell-penetrating peptide buforin IIb (Bu) was used. A stretch of seven consecutive phenylalanine residues (7F) was used as the rGO-binding sequence. Various effects of tetraglycine (4G) and tetra-aspartate (4D) as spacers between the biologically active Bu and the rGO-binding 7F sequences were compared. All chimeric peptides had α-helical structures at the carboxyl-terminal sequence, showing structural similarity to the α-helical structure of Bu alone. Free chimeric peptides composed of 7F-Bu, 7F4G-Bu, or 7F4D-Bu in solution exhibited cell-penetrating abilities similar to that of Bu alone. However, following attachment onto rGO nanosheets, the compositions of the chimeric peptides affected the biological activity of Bu. Following modification, the 7F4D-Bu chimeric peptide yielded higher cellular uptake of the rGO nanosheets than did the other chimeric peptides. The levels of cellular uptake of the rGO nanosheets modified with the chimeric peptides were further evaluated by measuring the photothermal effect after near-infrared laser irradiation. The cells treated with 7F4D-Bu-modified rGO showed the greatest increase in temperature upon irradiation, with the temperature reaching 58.3ºC. The 7F4D-Bu-modified rGO also exhibited the highest photothermal cell-killing activity upon near-infrared laser irradiation. Our results demonstrate the utility of chimeric peptide engineering for simple and facile one-step non-covalent modification of rGO. The chimeric peptide composed of 7F4D can be further used to tether various functional peptides onto rGO nanosheets.
    RSC Advances 05/2015; DOI:10.1039/C5RA03080C · 3.71 Impact Factor
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    ABSTRACT: Here, we report reduced graphene oxide (rGO) nanosheets anchoring receptor-specific polyaptamer nanothreads for targeted drug delivery. DNA polyaptamer nanothreads of protein tyrosine kinase 7 receptor (PTK7) were synthesized by rolling cycle amplification. To strengthen the anchoring of polyaptamer nanothreads onto rGO, oligoT bridge domain was introduced between each repeating PTK7 aptamer sequence. As compared to PTK7 polyaptamer nanothreads alone, PTK7 polyaptamer nanothreads with 22-mer oligoT bridges (PNT) showed higher anchoring capacity onto rGO nanosheets. Nanothread-coated surface morphology of PNTrGO was observed. Coating of PNT did not affect the sizes of rGO, but reduced the zeta potential. In PTK7-negative Ramos cells, the uptake of PNT-anchored rGO (PNTrGO) did not differ from that of oligoT-bridged scrambled polyaptamer-anchored rGO (SNTrGO). However, in CCRF-CEM leukemia cells overexpressing PTK7, the uptake of PNTrGO was 2.1-fold higher than that of SNTrGO after 15 min pulse. In vivo distribution to CCRF-CEM tumor tissues was 2.8-fold higher in PNTrGO than in SNTrGO at 48 h post-injection. In CCRF-CEM xenografted mice, intravenously administered doxorubicin (Dox)-loaded PNTrGO showed the higher antitumor activity than other groups, reducing the tumor weight down to 12% of tumor weights of untreated mice. These results suggest the potential of PNTrGO for target-specific drug delivery nanoplatform. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Biomaterials 04/2015; 48. DOI:10.1016/j.biomaterials.2015.01.009 · 8.31 Impact Factor
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    ABSTRACT: Here, we report the immunogenicity of a sublingually delivered, trivalent human papillomavirus (HPV) DNA vaccine encapsidated in a human endogenous retrovirus (HERV) envelope-coated, nonreplicable, baculovirus nanovector. The HERV envelope-coated, nonreplicable, baculovirus-based DNA vaccine, encoding HPV16L1, -18L1 and -58L1 (AcHERV-triHPV), was constructed and sublingually administered to mice without adjuvant. Following sublingual (SL) administration, AcHERV-triHPV was absorbed and distributed throughout the body. At 15 minutes and 1 day post-dose, the distribution of AcHERV-triHPV to the lung was higher than that to other tissues. At 30 days post-dose, the levels of AcHERV-triHPV had diminished throughout the body. Six weeks after the first of three doses, 1×108 copies of SL AcHERV-triHPV induced HPV type-specific serum IgG and neutralizing antibodies to a degree comparable to that of IM immunization with 1×109 copies. AcHERV-triHPV induced HPV type-specific vaginal IgA titers in a dose-dependent manner. SL immunization with 1×1010 copies of AcHERV-triHPV induced Th1 and Th2 cellular responses comparable to IM immunization with 1×109 copies. Molecular imaging revealed that SL AcHERV-triHPV in mice provided complete protection against vaginal challenge with HPV16, HPV18, and HPV58 pseudoviruses. These results support the potential of SL immunization using multivalent DNA vaccine in baculovirus nanovector for induction of mucosal, systemic, and cellular immune responses.
    PLoS ONE 03/2015; 10(3):e0119408. DOI:10.1371/journal.pone.0119408 · 3.53 Impact Factor
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    ABSTRACT: The intention of this research was to prepare and compare various solubility-enhancing nanoparticulated systems in order to select a nanoparticulated formulation with the most improved oral bioavailability of poorly water-soluble fenofibrate. The most appropriate excipients for different nanoparticulated preparations were selected by determining the drug solubility in 1% (w/v) aqueous solutions of each carrier. The polyvinylpyrrolidone (PVP) nanospheres, hydroxypropyl-β-cyclodextrin (HP-β-CD) nanocorpuscles, and gelatin nanocapsules were formulated as fenofibrate/PVP/sodium lauryl sulfate (SLS), fenofibrate/HP-β-CD, and fenofibrate/gelatin at the optimized weight ratios of 2.5:4.5:1, 1:4, and 1:8, respectively. The three solid-state products were achieved using the solvent-evaporation method through the spray-drying technique. The physicochemical characterization of these nanoparticles was accomplished by powder X-ray diffraction, differential scanning calorimetry, scanning electron microscopy, and Fourier-transform infrared spectroscopy. Their physicochemical properties, aqueous solubility, dissolution rate, and pharmacokinetics in rats were investigated in comparison with the drug powder. Among the tested carriers, PVP, HP-β-CD, gelatin, and SLS showed better solubility and were selected as the most appropriate constituents for various nanoparticulated systems. All of the formulations significantly improved the aqueous solubility, dissolution rate, and oral bioavailability of fenofibrate compared to the drug powder. The drug was present in the amorphous form in HP-β-CD nanocorpuscles; however, in other formulations, it existed in the crystalline state with a reduced intensity. The aqueous solubility and dissolution rates of the nanoparticles (after 30 minutes) were not significantly different from one another. Among the nanoparticulated systems tested in this study, the initial dissolution rates (up to 10 minutes) were higher with the PVP nanospheres and HP-β-CD nanocorpuscles; however, neither of them resulted in the highest oral bioavailability. Irrespective of relatively retarded dissolution rate, gelatin nanocapsules showed the highest apparent aqueous solubility and furnished the most improved oral bioavailability of the drug (~5.5-fold), owing to better wetting and diminution in crystallinity. Fenofibrate-loaded gelatin nanocapsules prepared using the solvent-evaporation method through the spray-drying technique could be a potential oral pharmaceutical product for administering the poorly water-soluble fenofibrate with an enhanced bioavailability.
    International Journal of Nanomedicine 03/2015; 10:1819-30. DOI:10.2147/IJN.S78895 · 4.20 Impact Factor
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    ABSTRACT: Here, we report the pharmacokinetics and in vivo fate of intra-articularly transplanted human mesenchymal stem cells in comparison with those of intravenoulys administered cells. Bone marrow-derived human clonal mesenchymal stem cells (hcMSC) were transplanted to nude mice via intravenous or intra-articular routes. The numbers of hcMSC in blood and tissue samples were measured by quantitative real time-polymerase chain reaction (qPCR) with human Alu as a detection marker. Following intra-articular transplantation, the blood levels of hcMSC peaked 8 h post dose and gradually diminished, showing a 95-fold higher mean residence time than hcMSC delivered via the intravenous route. Unlike intravenously administered hcMSC, intra-articularly injected hcMSC were mainly retained at injection joint sites, where their levels 8 h post-dose were 116-fold higher than those in muscle tissues. Regardless of injection routes, biodistribution patterns did not significantly differ between normal and osteoarthritis-induced mice. Quantitiave analysis using hAlu-specific qPCR revealed that hcMSC levels in joint tissues were significantly higher than those in muscle tissues 120 d post dose. These dramatic differences in kinetic behavior, and fate of intra-articularly transplanted hcMSC compared with intravenously administered hcMSC may provide insights useful for the development of human mesenchymal stem cells for arthritis therapeutics.
    Stem Cells and Development 12/2014; DOI:10.1089/scd.2014.0240 · 4.20 Impact Factor
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    ABSTRACT: Here, we report reduced graphene oxide (rGO) nanosheets coated with an anti-angiogenic anticancer taurocholate derivative of low-molecular-weight heparin (LHT7) as a tumor-targeting nanodelivery platform for anticancer drugs. Surface coating of LHT7 onto rGO was confirmed using fluorescein isothiocyanate-labeled LHT7, monitored as fluorescence quenching due to associated rGO. Unlike plain rGO, LHT7-coated rGO (LHT-rGO) nanosheets maintained a stable dispersion under physiological conditions for at least 24h. Moreover, LHT-rGO provided greater loading capacity for doxorubicin (Dox) compared with uncoated rGO nanosheets. Following intravenous administration into KB tumor-bearing mice, in vivo tumor accumulation of LHT-rGO/Dox was 7-fold higher than that of rGO/Dox 24h post dosing. In tumor tissues, LHT-rGO/Dox was shown to localize not to the tumor vasculature, but rather to tumor cells. Intravenously administered LHT-rGO/Dox showed the greatest anti-tumor effect in KB-bearing mice, reducing tumor volume by 92.5%±3.1% compared to the untreated group 25days after tumor inoculation. TUNEL assays revealed that the population of apoptotic cells was highest in the group treated with LHT-rGO/Dox. Taken together, our results demonstrate that LHT-rGO nanosheets confer improved dispersion stability, tumor distribution and in vivo antitumor effects, and may be further developed as a potential active nanoplatform of various anticancer drugs.
    Journal of Controlled Release 06/2014; DOI:10.1016/j.jconrel.2014.06.026 · 7.26 Impact Factor
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    ABSTRACT: Despite the progress of conventional vaccines, improvements are clearly required due to concerns about the weak immunogenicity of these vaccines, intrinsic instability in vivo, toxicity, and the need for multiple administrations. To overcome such problems, nanotechnology platforms have recently been incorporated into vaccine development. Nanocarrier-based delivery systems offer an opportunity to enhance the humoral and cellular immune responses. This advantage is attributable to the nanoscale particle size, which facilitates uptake by phagocytic cells, the gut-associated lymphoid tissue, and the mucosa-associated lymphoid tissue, leading to efficient antigen recognition and presentation. Modifying the surfaces of nanocarriers with a variety of targeting moieties permits the delivery of antigens to specific cell surface receptors, thereby stimulating specific and selective immune responses. In this review, we introduce recent advances in nanocarrier-based vaccine delivery systems, with a focus on the types of carriers, including liposomes, emulsions, polymer-based particles, and carbon-based nanomaterials. We describe the remaining challenges and possible breakthroughs, including the development of needle-free nanotechnologies and a fundamental understanding of the in vivo behavior and stability of the nanocarriers in nanotechnology-based delivery systems.
    Asian Journal of Pharmaceutical Sciences 06/2014; 9(5). DOI:10.1016/j.ajps.2014.06.002
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    ABSTRACT: Previously, we developed a non-replicating recombinant baculovirus coated with human endogenous retrovirus envelope protein (AcHERV) for enhanced cellular delivery of human papillomavirus (HPV) 16L1 DNA. Here, we report the immunogenicity of an AcHERV-based multivalent HPV nanovaccine in which the L1 segments of HPV 16, 18, and 58 genes were inserted into a single baculovirus genome of AcHERV. To test whether gene expression levels were affected by the order of HPV L1 gene insertion, we compared the efficacy of bivalent AcHERV vaccines with the HPV 16L1 gene inserted ahead of the 18L1 gene (AcHERV-HP16/18L1) with that of AcHERV with the HPV 18L1 gene inserted ahead of the 16L1 gene (AcHERV-HP18/16L1). Regardless of the order, the bivalent AcHERV DNA vaccines retained the immunogenicity of monovalent AcHERV-HP16L1 and AcHERV-HP18L1 DNA vaccines. Moreover, the immunogenicity of bivalent AcHERV-HP16/18L1 was not significantly different from that of AcHERV-HP18/16L1. In challenge tests, both bivalent vaccines provided complete protection against HPV 16 and 18 pseudotype viruses. Extending these results, we found that a trivalent AcHERV nanovaccine encoding HPV 16L1, 18L1, and 58L1 genes (AcHERV-HP16/18/58L1) provided high levels of humoral and cellular immunogenicity against all three subtypes. Moreover, mice immunized with the trivalent AcHERV-based nanovaccine were protected from challenge with HPV 16, 18, and 58 pseudotype viruses. These results suggest that trivalent AcHERV-HPV16/18/58L1 could serve as a potential prophylactic baculoviral nanovaccine against concurrent infection with HPV 16, 18, and 58.
    PLoS ONE 04/2014; 9(4):e95961. DOI:10.1371/journal.pone.0095961 · 3.53 Impact Factor
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    ABSTRACT: Here, we report that glucagon-like peptide-1 analogue liraglutide could enhance survival of human bone marrow-derived mesenchymal stem cells (hMSCs) following co-delivery in fibrin gel matrix. The hMSCs were treated with various concentrations (≤100 nM) of liraglutide. After 48 h, 100 nM liraglutide-treated hMSCs showed 1.4-fold higher cell viability than untreated hMSCs. Calcein staining for live cells and trypan blue staining for dead cells provided visual evidences that treatment of hMSCs with liraglutide increased cell survival. To evaluate the cell survival of hMSCs after in vivo transplantation, genomic DNA of hMSCs was quantified by quantitative real-time polymerase chain reaction by detecting human Alu element. Four days after transplantation, the survival of hMSCs co-transplanted with liraglutide (1.9 μg/kg) was 7.7-fold higher than that of plain hMSCs formulation. Taken together, our findings suggest the potential of liraglutide as a transplantation adjuvant for increasing in vivo survival of hMSCs.
    04/2014; 45(2):143-149. DOI:10.1007/s40005-014-0156-x
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    ABSTRACT: Anticancer chemotherapy usually involves the administration of several anticancer drugs that differ in their action mechanisms. Here, we aimed to test whether the combination of omacetaxine mepesuccinate (OMT) and doxorubicin (DOX) could show synergism, and whether the liposomal co-delivery of these two drugs could enhance their antitumor effects in cervical carcinoma model. OMT-loaded liposomes (OL) were prepared by loading the drug in the lipid bilayers. OL were then electrostatically complexed with DOX, yielding double-loaded liposomes (DOL). DOX-loaded liposomes (DL) were formulated by electrostatic interaction with negatively charged empty liposomes (EL). The combination index (CI) values were calculated to evaluate the synergism of two drugs. In vitro antitumor effects against HeLa cells were measured using CCK-8, calcein staining, and crystal violet staining. In vivo antitumor effects of various liposomes were tested using HeLa cell-bearing mice. Combination of DOX and OMT had ratio-dependent synergistic activities, with very strong synergism observed at a molar ratio of 4:1 (DOX:OMT). The sizes of EL, DL, OL, and DOL did not significantly differ, but the zeta potentials of DL and DOL were slightly higher than those of OL and EL. In vitro, DOL showed higher antitumor activity than OL, DL or EL in cervical carcinoma HeLa cells. In vivo, unlike other liposomes, DOL reduced the tumor growths by 98.6% and 97.3% relative to the untreated control on day 15 and 25 after the cessation of treatment, respectively. These results suggest that liposomal co-delivery of DOX and OMT could synergistically potentiate antitumor effects.
    Pharmaceutical Research 02/2014; 31(8). DOI:10.1007/s11095-014-1317-3 · 3.95 Impact Factor
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    ABSTRACT: Here, we report the effect of structure on the biological properties of photoresponsive carbon nanomaterials. Poloxamer 407-functionalized single-walled carbon nanotubes (PSWCNT) and poloxamer 407-functionalized graphene nanosheets (PGNS) exhibited similar physical stability and heating capacities after irradiation with an 808 nm near-infrared (NIR) laser. Despite sharing common physical properties, the cellular uptake of the PSWCNT and PGNS differed significantly. Cancer cells treated with PGNS took up a higher quantity of the nanosheets than of the PSWCNT and displayed a higher rate of cancer cell killing upon laser irradiation. Structure of carbon nanomaterials also affected the in vivo behaviors. PGNS could circulate in the blood 2.2 times longer than that of the PSWCNT. PGNS accumulated in the SCC tumor tissues to a greater degree than did PSWCNT over 7 days. NIR irradiation resulted in the complete ablation of tumor tissues in the PGNS-treated group but not in the other groups. After NIR irradiation, 100% of the PGNS-treated and NIR-irradiated mice survived until day 70. These results suggest the importance of structure in controlling the in vivo behaviors of carbon nanomaterials. Moreover, the results indicate the structural advantages of nanosheets over nanotubes in the enhancement of photothermal anticancer effects.
    Biomaterials 02/2014; 35(13). DOI:10.1016/j.biomaterials.2014.01.043 · 8.31 Impact Factor
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    ABSTRACT: Graphene-based nanosheets (GNS) are atomic-thickness monolayers of hexagonally arranged, graphite-derived carbon atoms that may be composed of graphene, graphene oxide, or reduced graphene oxide. They have attracted tremendous interest for their potential in pharmaceutical applications, due to their unique physical, chemical, and mechanical properties GNS exhibit highly uniform surface areas and may have hydroxyl (-OH), epoxide (-O-), and carboxyl functional groups at their basal surfaces and plane edges, depending on their oxidized and reduced surface properties. GNS show high-level optical absorption of near-infrared (NIR) light and elevate the temperature of nearby environments. Furthermore, they can be loaded with anticancer drugs via hydrophobic interactions, stacking, or electrostatic binding. Given these properties, GNS can be used in chemotherapy, photodynamic therapy, photothermal therapy, and theranostics. However, although GNS appear to have far-reaching potential in the field of biomedical research, their widespread pharmaceutical application has been limited by issues such as poor stability in physiological buffers, undefined mechanisms of cellular uptake, toxicity problems, and a lack of standard preparation methods. Here, we review the current pharmaceutical applications of GNS, focusing on chemotherapy, phototherapy, combo therapy and theranostic applications with challenging issues.
    Current pharmaceutical biotechnology 01/2014; DOI:10.2174/1389201015666140113113222 · 2.51 Impact Factor
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    ABSTRACT: Here, we report a double-stranded, dual-anchored, fluorescent aptamer on reduced graphene oxide (rGO) for the sensitive, selective, and speedy detection of a target protein in biological samples. This nano detector is composed of a target protein-specific fluorescent aptamer with BHQ1 as one anchoring moiety that forms double-stranded sequences with a complementary oligonucleotide sequence with BHQ1 as the other anchoring moiety, anchored to rGO nanosheets. The double-stranded and dual-anchored aptamer on rGO nanosheets (DAGO) exhibited 7.3-fold higher fluorescence intensities compared to a single-stranded, single-anchored fluorescent aptamer on rGO. As a model target protein, interferon-γ was used. DAGO detected the target protein, with linearity over a five-orders-of-magnitude concentration range (0.1 ng/ml-10 μg/ml) in buffer and human serum. DAGO was highly specific for the target protein, exhibiting little changes in fluorescence intensity in response to the non-target proteins, interleukin-2 and tumor necrosis factor-α. Moreover, DAGO allowed rapid quantification of the target protein in human immunodeficiency virus-positive patient serum samples. DAGO-based detection was complete in less than 10 min. Our results indicate that the DAGO provides new opportunities for the rapid and specific detection of target proteins in biological samples and could be widely applied to quantitate various target proteins by replacing the aptamer sequences.
    Biomaterials 01/2014; 35(9). DOI:10.1016/j.biomaterials.2013.12.058 · 8.31 Impact Factor
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    ABSTRACT: The sub-acute toxic effects following repetitive intramuscular injection of two cervical cancer vaccines newly developed against human papillomaviruse (HPV)16/58/18 and HPV16 were investigated in female ICR (CrljOri: CD1) mice, and the no-observedadverse- effect-level (NOAEL) of the cervical cancer vaccines was estimated. Female ICR mice (n=15 in each group) were exposed to a 1:1 mixture of two cervical cancer vaccines by repetitive intramuscular injection (once a week, 5 times) for 5 weeks. Mortality, body weight, organ weight, hematological/biochemical parameters, and histopathological effects were examined at different concentrations (0, 1×10(8), 5×10(8), and 2.5×10(9) copies/animal) of the cervical cancer vaccines. The cervical cancer vaccines did not show toxic responses for body weight, absolute/ relative organ weight, hematological/biochemical parameters, or histopathological parameters. Female ICR mice exposed to vaccines for cervical cancer did not show any toxic response. We suggest that a NOAEL of the vaccine following repetitive intramuscular injection for 5 weeks is >2.5×10(9) copies/animal.
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    ABSTRACT: Estimation of the efficacy of mosquito repellents requires both laboratory and field tests. The results of field tests are more meaningful, but the safety of volunteers in such tests may be a significant concern. In the current study, we compared tests of mosquito repellent efficacy under semifield conditions in an outdoor enclosure with those under laboratory and field conditions. In this study, we assessed the efficacy of N,N-diethyl-meta-toluamide under laboratory conditions with human volunteers and under semifield and field conditions with Centers for Disease Control and Prevention traps and experimental mice. A semifield test may be a suitable replacement for the more difficult field test for assessment of mosquito repellent efficacy. Semifield tests should be considered when developing new guidelines for testing.
    Journal of Medical Entomology 01/2014; 51(1):182-8. DOI:10.1603/ME13081 · 1.82 Impact Factor
  • Journal of Controlled Release 01/2014; 189:80–89. · 7.26 Impact Factor
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    ABSTRACT: This study aimed to evaluate the effect of biocompatible polymers on the physicochemical and dissolution properties of poorly water-soluble drugs in nanoparticle systems. Four types of nanoparticles containing poorly water-soluble fenofibrate were prepared using solvent evaporation technique with different biocompatible polymers such as polyvinylpyrrolidone (PVP), hydroxypropylmethyl cellulose (HPMC), carbopol and ethylcellulose. Their physicochemical properties were investigated using scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffraction. The solubility and dissolution of nanoparticle-entrapped fenofibrate were compared with those of free drug powder. Biocompatible polymers affected the morphology and sizes of fenofibrate nanoparticles. PVP or carbopol-based nanoparticles showed spherical appearance, whereas HPMC or ethylcellulose-based nanoparticles formed aggregates with irregular shape. The particle sizes increased in the order of the nanoparticle prepared with carbopol ≤ PVP HPMC > carbopol > ethylcellulose. The enhanced solubility and dissolution of poorly water-soluble fenofibrate via nanoparticle system did not depend on particle size but on crystallinity. In conclusion, in nanoparticle development of poorly water-soluble drugs such as fenofibrate, the nature of biocompatible polymers plays an important role in the physicochemical and dissolution of poorly water-soluble drugs in the nanoparticles.
    12/2013; 43(6). DOI:10.1007/s40005-013-0100-5
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    ABSTRACT: Human endogenous retrovirus (HERV) envelope protein-coated, baculovirus vector-based HPV 16 L1 (AcHERV-HPV16L1) is a non-replicating recombinant baculoviral vaccine. Here, we report an initial evaluation of the preclinical safety of AcHERV-HPV16L1 vaccine. In an acute toxicity study, a single administration of AcHERV-HPV16L1 DNA vaccine given intramuscularly (i.m.) to mice at a dose of 1 × 10(8) plaque-forming units (PFU) did not cause significant changes in body weight compared with vehicle-treated controls. It did cause a brief increase in the weights of some organs on day 15 post-treatment, but by day 30, all organ weights were not significantly different from those in the vehicle-treated control group. No hematological changes were observed on day 30 post-treatment. In a range-finding toxicity study with three doses of 1 × 10(7) , 2 × 10(7) and 5 × 10(7) PFU once daily for 5 days, the group treated with 5 × 10(7) PFU showed a transient decrease in the body weights from day 5 to day 15 post-treatment, but recovery to the levels similar to those in the vehicle-treated control group by post-treatment day 20. Organ weights were slightly higher for lymph nodes, spleen, thymus and liver after repeated dosing with 5 × 10(7) PFU on day 15, but had normalized by day 30. Moreover, repeated administration of AcHERV-HPV16L1 did not induce myosin-specific autoantibody in serum, and did not cause immune complex deposition or tissue damage at injection sites. Taken together, these results provide preliminary evidence of the preclinical safety of AcHERV-based HPV16L1 DNA vaccines in mice. Copyright © 2012 John Wiley & Sons, Ltd.
    Journal of Applied Toxicology 12/2013; 33(12). DOI:10.1002/jat.2815 · 3.17 Impact Factor
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    ABSTRACT: Despite the advantages of DNA vaccines, overcoming their lower efficacy relative to that of conventional vaccines remains a challenge. Here, we constructed a human endogenous retrovirus (HERV) envelope-coated, nonreplicable, baculovirus-based HA vaccine against swine influenza A/California/04/2009(H1N1) hemagglutin (HA) (AcHERV-sH1N1-HA) as an alternative to conventional vaccines and evaluated its efficacy in two strains of mice, BALB/c and C57BL/6. A commercially available, killed virus vaccine was used as a positive control. Mice were intramuscularly administered AcHERV-sH1N1-HA or the commercial vaccine and subsequently given two booster injections. Compared with the commercial vaccine, AcHERV-sH1N1-HA induced significantly higher levels of cellular immune responses in both BALB/c and C57BL/6 mice. Unlike cellular immune responses, humoral immune responses depended on the strain of mice. Following immunization with AcHERV-sH1N1-HA, C57BL/6 mice showed HA-specific IgG titers 10- to 100-fold lower than those of BALB/c mice. In line with the different levels of humoral immune responses, the survival of immunized mice after intranasal challenge with sH1N1 virus (A/California/04/2009) depended on the strain. After challenge with 10-times the median lethal dose (MLD50) of sH1N1 virus, 100% of BALB/c mice immunized with the commercial vaccine or AcHERV-sH1N1-HA survived. In contrast, C57BL/6 mice immunized with AcHERV-sH1N1-HA or the commercial vaccine showed 60% and 70% survival respectively, after challenge with sH1N1 virus. In all mice, virus titers and results of histological analyses of lung tissues were consistent with the survival data. Our results indicate the importance of humoral immune response as a major defense system against influenza viral infection. Moreover, the complete survival of BALB/c mice immunized with AcHERV-sH1N1-HA after challenge with sH1N1 virus suggests the potential of baculoviral vector-based vaccines to achieve an efficacy comparable to that of killed virus vaccines.
    PLoS ONE 11/2013; 8(11):e80762. DOI:10.1371/journal.pone.0080762 · 3.53 Impact Factor
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    ABSTRACT: We synthesized and evaluated (64)Cu-labeled tetraiodothyroacetic acid (tetrac)-conjugated liposomes for PET imaging of tumor angiogenesis, because tetrac inhibits angiogenesis via integrin αVβ3. Tetrac-PEG-DSPE and DOTA-PEG-DSPE were synthesized and formulated with other lipids into liposomes. The resulting tetrac/DOTA-liposomes were labeled with (64)Cu at 40 °C for 1 h and purified using a PD-10 column. (64)Cu-DOTA-liposomes were also prepared for comparison. Human aortic endothelial cell (HAEC) binding studies were performed by incubating the liposomes with the cells at 37 °C. MicroPET imaging followed by tissue distribution study was carried out using U87MG tumor-bearing mice injected with tetrac/(64)Cu-DOTA-liposomes or (64)Cu-DOTA-liposomes. HAEC binding studies exhibited that tetrac/(64)Cu-DOTA-liposomes were avidly taken up by the cells from 1.02 %ID at 1 h to 11.89 %ID at 24 h, while (64)Cu-DOTA-liposomes had low uptake from 0.47 %ID at 1 h to 1.57 %ID at 24 h. MicroPET imaging of mice injected with tetrac/(64)Cu-DOTA-liposomes showed high radioactivity accumulation in the liver and spleen. ROI analysis of the tumor images revealed 1.93±0.12 %ID/g at 1 h and 2.70±0.36 %ID/g at 22 h. In contrast, tumor ROI analysis of (64)Cu-DOTA-liposomes revealed 0.54±0.08 %ID/g at 1 h and 0.52±0.09 %ID/g at 22 h. Tissue distribution studies confirmed that the tumor uptakes of tetrac/(64)Cu-DOTA-liposomes and (64)Cu-DOTA-liposomes were 1.75±0.03 %ID/g and 0.36±0.01 %ID/g at 22 h, respectively. These results demonstrate that tetrac/(64)Cu-DOTA-liposomes have significantly enhanced tumor uptake compared to (64)Cu-DOTA-liposomes due to tetrac conjugation. Further studies are warranted to reduce the liver and spleen uptake of tetrac/(64)Cu-DOTA-liposomes.
    Nuclear Medicine and Biology 09/2013; 40(8). DOI:10.1016/j.nucmedbio.2013.08.003 · 2.41 Impact Factor

Publication Stats

3k Citations
565.75 Total Impact Points

Institutions

  • 1988–2015
    • Seoul National University
      • • Research Institute of Pharmaceutical Sciences
      • • College of Pharmacy
      Sŏul, Seoul, South Korea
  • 2006–2013
    • Korea University
      • Department of Biotechnology
      Sŏul, Seoul, South Korea
  • 2011–2012
    • Konkuk University
      • • College of Animal Bioscience and Technology
      • • Department of Animal Biotechnology
      Sŏul, Seoul, South Korea
  • 2007–2010
    • Hanyang University Medical Center
      Sŏul, Seoul, South Korea
    • Yeungnam University
      • College of Pharmacy
      Asan, South Chungcheong, South Korea
  • 2005
    • Ewha Womans University
      Sŏul, Seoul, South Korea
  • 2004
    • Hanyang University
      Sŏul, Seoul, South Korea
  • 2001–2004
    • CHA University
      • College of Medicine
      Sŏul, Seoul, South Korea