Pharmacokinetics and Biodistribution of Paclitaxel Loaded in Pegylated Solid Lipid Nanoparticles after Intravenous Administration

Rihua LI,이미경,은재순 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.2

In an effort to develop an alternative formulation of paclitaxel (PTX) suitable for intravenous administration, PTX-loaded sterically stabilized solid lipid nanoparticles (SLNs) were prepared and their pharmacokinetics and biodistribution were investigated. The pegylated SLNs were comprised of trimyristin (TM) as a solid lipid core and egg phosphatidylcholine and pegylated phospholipid as stabilizers. The prepared pegylated TM-SLNs containing PTX exhibited monodispersed size distribution with 217.4 ± 32.8 nm of mean diameter and 99% of distribution was smaller than 556.2 ± 89.9 nm. After PTX in the pegylated TM-SLNs or commercial product, Taxol^®, was intravenously administered into femoral vein of rats, concentrations of PTX in plasma and organs such as liver, spleen, kidney, heart and lung were analyzed by HPLC following liquid extraction. Plasma profile of PTX for pegylated TM-SLNs was similar to that for Taxol^®, with no statistically significant difference at each time point, although mean plasma levels of PTX at each point tended to be slightly lower in pegylated TM-SLNs than in Taxol^®. PTX in the pegylated TM-SLNs was taken up mainly into reticuloendothelial system showing 8-fold and 3-fold higher levels in liver and spleen, respectively, 8 h after administration compared to PTX in Taxol^®. Meanwhile, PTX levels in kidney, heart and lung were not different between two formulations. There were no statistically significant differences in pharmacokinetic parameters. Taken together the results, the pegylated TM-SLNs provided similar circulation compared with commercial formulation, Taxol^®.

Gene isolation and characterization of a dominant dwarf mutant, D-h, in rice

Rihua Piao,Sang-Ho Chu,Yoye Yu,Donggwan Kim,Sunghan Kim,Hee-Jong Koh 한국육종학회 2013 한국육종학회 심포지엄 Vol.2013 No.07

Plant height is an important agronomic trait that affects grain yield. Previously, we reported a novel semi-dominant dwarf mutant, D-h, derived from chemical mutagenesis using N-methyl-N-nitrosourea(MNU) on a japonica rice cultivar, Hwacheongbyeo. In this study, we cloned the gene responsible for the dwarf mutant using the map-based approach. Fine mapping revealed that the mutant gene was located on the short arm of chromosome 1 in a 48 kb region. Sequencing of the candidate genes and rapid amplification of cDNA ends-polymerase chain reaction(RACE-PCR) analyses identified the gene, d-h, which encodes a protein of unknown function, but whose sequence is conserved in other cereal crops. Real-time (RT)-PCR analysis and promoter activity assay showed that the d-h gene was primarily expressed in the nodes and the panicle. In the D-h mutant plant, the gene was found to carry a 63-bp deletion in the ORF region, which was confirmed to be directly responsible for the mutant’s gain of a functional phenotype by subsequent transgenic experiments. Since the mutant plants exhibit a defect in the GA response, but not in the GA synthetic pathway, it appears that the d-h gene may be involved in a GA signaling pathway.

Solid Lipid Nanoparticles as Drug Delivery System for Water-Insoluble Drugs

Li, Rihua,Lim, Soo-Jeong,Choi, Han-Gon,Lee, Mi-Kyung The Korean Society of Pharmaceutical Sciences and 2010 Journal of Pharmaceutical Investigation Vol.40 No.special

Solid lipid nanoparticles (SLNs) have emerged to combine the advantages of polymeric nanoparticles and lipid emulsions in early 1990s. SLNs can present several desirable properties derived from the solid state core. When formulating SLNs, there should be careful considerations about the physical state of the inner solid lipid core and its polymorphism and supercooling behavior. In this review, SLNs were compared to lipid emulsion and emulsion of supercooled melt to understand the unusual behaviors compared to lipid emulsions and to have insights into stability and release mechanism. SLNs have been regarded as biocompatible system because lipids are usually well-tolerable ingredients than polymers. Several studies showed good tolerability of SLNs in terms of cytotoxicity and hemolysis. Similar to various other nanoparticulate drug delivery systems, SLNs can also change biodistribution of the incorporated drugs in a way to enhance therapeutic effect. Most of all, large scale production of SLNs was extablished wihtout using organic solvents. Although there is no SLN product in the market till date, several advantagious properties of SLNs and the progress we have seen so far would make commercial product of SLNs possible before long and encourage research community to apply SLN-based formulations for water-insoluble drugs.

Combination of Curcumin and Paclitaxel-loaded Solid Lipid Nanoparticles to Overcome Multidrug Resistance

Li, Rihua,Xu, Wenting,Eun, Jae-Soon,Lee, Mi-Kyung The Korean Society of Pharmaceutical Sciences and 2011 Journal of Pharmaceutical Investigation Vol.41 No.6

Multi-drug resistance (MDR) has been known as a major hurdle in cancer chemotherapy. One of the most clinically significant causes of MDR was the efflux of anticancer agents mediated by p-glycoprotein (p-gp) over-expressed in MDR cancer cells. To overcome MDR, there have been several strategies such as co-administration with p-gp inhibitors and encapsulation of anticancer drugs into drug delivery systems. In the present study, curcumin was evaluated for its potential as p-gp inhibitor and MDR reversal activity when combined with paclitaxel incorporated into lipid nanoparticles (PTX/LN). Western blot assay showed curcumin did not modulate the level of p-gp expression in MCF-7/ADR which is a MDR variant of human breast cancer cell line, MCF-7, and over-expresses p-gp. However, curcumin inhibited p-gp-mediated efflux of calcein in a dose-dependent manner even though it showed lower activity compared to verapamil, a well-known p-gp inhibitor. Incorporation of paclitaxel into lipid nanoparticles partially recovered the anticancer activity of paclitaxel in MCF-7/ADR. The combined use of curcumin and PTX/LN exhibited further full reversal of MDR, suggesting susceptibility of PTX/LN to the efflux system. In conclusion, combined approach of using p-gp inhibitors and incorporation of the anticancer agents into nano-delivery systems would be an efficient strategy to overcome MDR.

Iron overload by transferrin receptor protein 1 regulation plays an important role in palmitate‐induced insulin resistance in human skeletal muscle cells

Cui, Rihua,Choi, Sung-E,Kim, Tae Ho,Lee, Hwa Joung,Lee, Soo Jin,Kang, Yup,Jeon, Ja Young,Kim, Hae Jin,Lee, Kwan-Woo Federation of American Society for Experimental Bi 2019 The FASEB Journal Vol.33 No.2

The Relationship between Chinese Parents' Reaction to Children's Negative Emotions and Children's Understanding of Emotions

Jin, Rihua,Lee, Young Korean Association of Child Studies 2014 Child studies in Asia-Pacific context Vol.3 No.2

The purpose of this study was to investigate Chinese parents' reaction to their children's negative emotions and how these reactions relate to their children's understanding of emotions. Forty-two Chinese children (aged 4) and their parents participated in this study. Coping with Children's Negative Emotion Scale was given to parents to assess their reaction to their children's negative emotions. Children's emotional understanding was assessed using the modified emotional false-belief task and mixed emotion task. The results showed that Chinese parents gave supportive reactions more than non-supportive reactions to their children, and no difference in sex was found. The percentages of correct answers to false-belief task and mixed emotion task were low with no gender difference in both tasks. When age and sex of children were controlled, only fathers' supportive reactions to children's negative emotions significantly explained the variances in the level of children's understanding of emotions in both tasks. That is, children whose fathers showed greater supportive reactions to their negative emotions performed better at both tasks. It was concluded that fathers' supportive reactions to their children's negative emotions are very influential for emotional understanding among 4-year-old children in China.

Fine mapping and characterization of small round grain erect panicle mutant in rice

Yogendra Bordiya,Rihua Piao,Backki Kim,Hong-Yeol Kim,Hee-Jong Koh 한국육종학회 2012 한국육종학회 심포지엄 Vol.2012 No.07

Grain size is one of the most important trait determining yield in cereal crops, apart from number of grains per panicle, number of panicles per plant and 1000 seed weight. Other than grain characteristics, plant architecture is another very important factor influencing yield by affecting the amount plant surface area directly exposed to the sun light. Erect panicle is important morphological characteristic which helps in enhancing the yield by allowing sun light to fall directly on leaves unlike curved panicle which blocks sunlight and consequently reduce photosynthesis. A small round grain and erect panicle mutant was obtained by treating Hwacheong rice (japonica) with MNU (N-methyl-N-nitrosourea) chemical mutagen. Through bulked segregant analysis (BSA) using STS (Sequence-Tagged Sites) and SS-STS (Sub-species Specific Sequence-Tagged Site) markers we located the mutated gene on the long arm of chromosome 7 and narrowed down candidate region to 168.75kbp through fine mapping. Mutant manifested characteristics like reduced grain size and plant height, dense and erect panicle and relatively erect plant compared to the wild type. When we crossed the mutant with its parent (Hwacheong), F1 panicle and grain characteristics showed intermediate phenotype, therefore, we concluded that wild type allele of this gene shows incomplete dominance. Scanning electron microscopy(SEM) result shows that increase in width of mutant grain, which changes its shape, is due to increase in width of glume cells. Phenotypic examination shows that dense and erect panicle phenotype is result of reduction in length of rachis, primary and secondary branch.

Genotypic variation of embryo dent of rice grains

Yunjoo Lee,Gileung Lee,Rihua Piao,Sunmi Jang,Hee-Jong Koh 한국육종학회 2013 한국육종학회 심포지엄 Vol.2013 No.07

As the market demand on functionality rice has been increasing, embryo rice in which embryo residue remains even after milling has come to comsumers’ attention because rice embryo contains several functionality components. Consequently, development of rice varieties for higher rate of embryo adhesion to grains after milling has become one of the breeding objectives for quality improvement. In this study, we observed embryo dent of 49 commercial varieties and analyzed the relationship between embryo dent and grain size and shape. Embryo dent of rice grains varied 0.27 (Keunnun)~0.59 (Daerip 1) mm. Varieties Jinbu, Jinbo, Heugseol, Obong, Unkwang, and Cheongnam showed relatively deeper embryo dent, suggesting that they will be applicable in breeding for embryo rice. Embryo dent was correlated positively with grain width (r=0.53**) and grain size(r=0.34*), and negatively with grain width/length ratio (r= -0.38**). Strategies for breeding embryo rice were discussed in relation to embryo dent, grain size and shape.

Development of diagnostic DNA markers for eating quality of indica rice

Yunjoo Lee,Puji Lestari,Rihua Piao,Eunbyeol Koh,Sunmi Jang,Hee-Jong Koh 한국육종학회 2014 한국육종학회 심포지엄 Vol.2014 No.07

Rice eating quality is considered to be one of the top priorities in determining the agronomical value of rice. Thus the rapid evaluation of eating quality at early breeding generations in breeding programs for better eating quality is of great importance. However, it has been limited due to the complex nature of eating quality and the absence of standard evaluation method. In our previous study, we developed a evaluation method with a set of DNA markers that allows to predict the eating quality for japonica rices. Here we successfully developed another marker set for the eating quality of indica rices. We used multiple regression analysis to test 54 markers, which were preselected for their possible association with eating quality, using 24 indica varieties with different palatability scores. Of these markers, eighteen markers were found to be significantly associated with palatability according to sensory evaluation. Accordingly, a marker set in the model regression equation with a high R2 (0.997) was formulated to estimate indica rice palatability. Validation suggests that markers and the statistical parameters formulated by the equation could be a potential tool to predict the palatability of cooked Indonesian indica rice and could be reliable in developing country-dependent model equations for eating quality. This work was supported by a grant from the Next-Generation BioGreen 21 Program (Plant Molecular Breeding Center No. PJ008125), Rural Development Administration, Republic of Korea.

Fine mapping and candidate gene analysis of a new mutant gene for panicle apical abortion in rice

Md. Babul Akter,Rihua Piao,Backki Kim,Yunjoo Lee,Eunbyeol Koh,Hee-Jong Koh 한국육종학회 2013 한국육종학회 심포지엄 Vol.2013 No.07

The architecture of rice panicle is primarily determined by the arrangement of branches and spikelets, and it directly affects grain yield. We identified a mutant for panicle apical abortion from a japonica cultivar Hwacheongbyeo treated with N-methyl-N-nitrosourea. Under normal growth conditions, the mutant had multiple abnormal phenotypes, such as a slight reduction in plant height, narrow and dark green leaf blades, and small erect panicles with clear panicle apical abortion compared to the wild-type plants. Genetic analysis revealed that the panicle apical abortion was controlled by a single recessive gene, which is tentatively designated as paa. The paa gene was fine mapped at an interval of 71 kb flanked by STS markers aptn3 and S6685-1 at the long arm of chromosome 4. Sequence analysis of the candidate genes within the delimited region showed a single base-pair change corresponding to an amino acid substitution from glycine to glutamic acid. We expect that the paa gene will be a clue to uncover the molecular mechanism of panicle apical abortion and to maintain the panicle identity for grain yield in rice breeding programs.