Formulation and in vivo imaging evaluation of colonic targeting tablets prepared by a simple dry powder coating technique

Tung Nguyen-Thach,Nguyen Canh-Hung,Nguyen Van-Duong,Nguyen Thi-Hong-Thuy,Nguyen Van-Lam,Tran Cao-Son,Pham Thi-Minh-Hue 한국약제학회 2020 Journal of Pharmaceutical Investigation Vol.50 No.4

Purpose The study aimed firstly to determine the release behavior of the model drug (berberine chloride) from the dry coated tablets. The second objective of this study was to evaluate the exact location of the dry coated tablets in in vivo. Methods The colon targeting tablets were developed by dry powder coating technique on pan coater. The drug release behavior was determined in the three continuous mediums: pH 1.2; 7.4 and 6.8 plus pectinase. The location of the dry coated tablets in the gastrointestinal tract of human volunteers was observed through the X-ray imaging of the dry coated tablets containing the optimized radiocontrast agents. Results The release kinetics of berberine chloride from the dry coated tablets was mainly controlled by erosion and enzyme sensitive mechanism. The optimum dry coated tablets having the coating powders of pectin 102:HPMC K4 M (2:1) with the coating level of 200%, and the tablet core with BaSO4 10% and iobitridol 30% as radiocontrast agents were observed in the caecum and ascending colon of human volunteers after 5–6 h of oral administration. Conclusion The successful development of these dosage forms is believed to have a high potential in precisely monitoring the release of highly potent drugs such as anti-inflammatory drugs in bowel diseases.

<i>Streptococcus pneumoniae</i> ClpL Modulates Adherence to A549 Human Lung Cells through Rap1/Rac1 Activation

Nguyen, Cuong Thach,Le, Nhat-Tu,Tran, Thao Dang-Hien,Kim, Eun-Hye,Park, Sang-Sang,Luong, Truc Thanh,Chung, Kyung-Tae,Pyo, Suhkneung,Rhee, Dong-Kwon American Society for Microbiology 2014 Infection and immunity Vol.82 No.9

<P>Caseinolytic protease L (ClpL) is a member of the HSP100/Clp chaperone family, which is found mainly in Gram-positive bacteria. ClpL is highly expressed during infection for refolding of stress-induced denatured proteins, some of which are important for adherence. However, the role of ClpL in modulating pneumococcal virulence is poorly understood. Here, we show that ClpL impairs pneumococcal adherence to A549 lung cells by inducing and activating Rap1 and Rac1, thus increasing phosphorylation of cofilin (inactive form). Moreover, infection with a <I>clpL</I> mutant (Δ<I>clpL</I>) causes a greater degree of filopodium formation than D39 wild-type (WT) infection. Inhibition of Rap1 and Rac1 impairs filopodium formation and pneumococcal adherence. Therefore, ClpL can reduce pneumococcal adherence to A549 cells, likely via modulation of Rap1- and Rac1-mediated filopodium formation. These results demonstrate a potential role for ClpL in pneumococcal resistance to host cell adherence during infection. This study provides insight into further understanding the interactions between hosts and pathogens.</P>

TLR4 Mediates Pneumolysin-Induced ATF3 Expression through the JNK/p38 Pathway in Streptococcus pneumoniae-Infected RAW 264.7 Cells

Nguyen, Cuong Thach,Kim, Eun-Hye,Luong, Truc Thanh,Pyo, Suhkneung,Rhee, Dong-Kwon Korean Society for Molecular and Cellular Biology 2015 Molecules and cells Vol.38 No.1

Activating transcription factor-3 (ATF3) acts as a negative regulator of cytokine production during Gram-negative bacterial infection. A recent study reported that ATF3 provides protection from Streptococcus pneumoniae infection by activating cytokines. However, the mechanism by which S. pneumoniae induces ATF3 after infection is still unknown. In this study, we show that ATF3 was upregulated via Toll-like receptor (TLR) pathways in response to S. pneumoniae infection in vitro. Induction was mediated by TLR4 and TLR2, which are in the TLR family. The expression of ATF3 was induced by pneumolysin (PLY), a potent pneumococcal virulence factor, via the TLR4 pathway. Furthermore, ATF3 induction is mediated by p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK). Thus, this study reveals a potential role of PLY in modulating ATF3 expression, which is required for the regulation of immune responses against pneumococcal infection in macrophages.

ATF3 Confers Resistance to Pneumococcal Infection Through Positive Regulation of Cytokine Production

Nguyen, Cuong Thach,Kim, Eun-Hye,Luong, Truc Thanh,Pyo, Suhkneung,Rhee, Dong-Kwon Oxford University Press 2014 The Journal of Infectious Diseases Vol.210 No.11

<P><B><I>Background.</I></B> Activating transcription factor–3 (ATF3) is known as a suppressor of cytokine production after exposure to lipopolysaccharide or during gram-negative bacterial infection. However, the mechanism by which ATF3 regulates innate immunity against gram-positive bacterial infection, particularly <I>Streptococcus pneumoniae</I>, remains unknown.</P><P><B><I>Methods.</I></B> The wild-type and ATF3 knock-out (KO) mice were infected intranasally (<I>i.n</I>) or intraperitoneally with <I>S. pneumoniae</I>, and bacterial colonization or survival rate was determined. Pneumococcal pneumonia was induced by <I>i.n</I> infection, and ATF3 level was determined by Western blot. ATF3 KO cells or ATF3 siRNA transfection were used to determine expression of ATF3 downstream genes. Enzyme-linked immunosorbent assay was used to examine cytokines levels.</P><P><B><I>Results.</I></B> ATF3 was highly expressed in various cell lines in vitro and in many organs in vivo. Pneumolysin was a novel inducer of ATF3. Pneumococcal infection induced ATF3, which subsequently stimulated production of cytokines (tumor necrosis factor [TNF]–α, interleukin [IL]–1β, and interferon [IFN]–γ). ATF3-mediated cytokine induction protected the host from pneumococcal infection. In the pneumonia infection model, the bacterial clearance of wild-type mice was more efficient than those of ATF3 KO mice.</P><P><B><I>Conclusions.</I></B> Taken together, we can conclude that ATF3 regulates innate immunity positively upon pneumococcus infection by enhancing TNF-α, IL-1β, and IFN-γ expression and modulating bacterial clearance.</P>

Effects of Supplemental Green LEDs to Red and Blue Light on the Growth, Yield and Quality of Hydroponic Cultivated Spinach (Spinacia oleracea L.) in Plant Factory

Nguyen Thi Phuong Dung(넨티덩),Tran Thi Thanh Huyen(트란티),Dong Cheol Jang(장동철),Il Seop Kim(김일섭),Nguyen Quang Thach(넨퀸탓) (사)한국생물환경조절학회 2020 생물환경조절학회지 Vol.29 No.2

본 연구는 폐쇄형 식물공장에서 시금치 수경재배시 세가지의 인공광이 생육, 광합성 및 품질에 미치는 영향을 규명하기 위해 수행되었다. 세가지 광 처리구는 적색 (660nm), 청색 (450nm) 및 녹색 (550nm) LED를 사용하여, R660 / B450 = 4/1 (RBL), R660 / B450 / G550 = 5/2/3 (WWL); R660 / B450 / G550 = 1/1/1 (WL) 비율로 혼합하였고, 동일한 광도로 설정하였다 (PPFD = 190 μmol‧m<SUP>-2</SUP>‧s<SUP>-1</SUP>). 생육조사결과 초장, 엽수는 WL이 가장 적었다. SPAD, 순광합성율, Fv/Fm, LAI, 근권부 생육은 RBL이 가장 높았고 통계적으로 유의하였다. 줄기, 잎, 뿌리의 생체중, 뿌리의 건물 중은 세가지 처리구에서 유의한 차이를 보였다. 대조적으로 WL의 칼륨의 함량은 WWL과 RBL 가운데 가장 높았지만, 반면 칼륨과 철의 함량은 RBL이 가장 높았다. 비타민C 함량도 시험구간 유의한 차이를 보였다. 질소와 옥살산 함량은 WL이 가장 높았고, 용해성 고체와 비타민C 함량은 RBL이 가장 높았다. 옥살산, 질소 함량은 WWL에서 감소하는 경향을 보였고, RBL의 옥살산 함량은 WL와 WWL과 차이가 없었다. 모든 처리구에서 Salmonella, E.coli. 는 감염되지 않았다. 결론적으로, RBL이 시금치의 생육에 적합하지만, 적색, 청색과 적정하게 혼합된 녹색광은 시금치의 생육에 긍정적인 영향을 미친다고 판단된다. The effect of three different light qualities on growth, photosynthesis, quality and safe parameters of hydroponic cultivated spinach (Spinacia oleracea L.) were investigated indoor. Three different light qualities were created of red (660 nm), blue (450 nm) and green (550 nm) LEDs corresponding at ratio R660/B450 = 4/1 (RBL); R660/B450/G550= 5/2/3 (WWL); R660/B450/G550 = 1/1/1 (WL), which were tested at the same intensity (PPFD =190 μmol m-2 s-1). The results showed that the plant height and leaf number were the lowest in WL treatment. The SPAD, Net photosynthesis rate Pn, Fv/Fm, Leaf area index LAI values and all parameters of root characteristics were the highest in RBL treatment and were significantly different from two others. Fresh weight of stem, leaf and root, dry weight of root in the three light qualities were significantly different. In contrast, the highest K<SUP>+</SUP> content in WL was different from WWL and RBL treatments, while Ca<SUP>2+</SUP> and Fe<SUP>2+</SUP> content were the highest in the RBL treatment. Vitamin C content was significantly different between the three treatments. nitrate and oxalic acid contents were the highest in WL treatment, whereas soluble–solids contents and vitamin C contents were the highest in RBL treatment. Oxalic acid, nitrate contents were observed tending reduced under WWL although oxalic acid content in RBL treatment was not different from WL and WWL treatments. In all three different light treatments were not detected Salmonella, E.coli. Our results suggest that RBL may be appropriate light for growth of spinach, but supplementary green light to a combination of red and blue LEDs at the reasonable rate can change the quality of spinach in a positive direction. Hydroponic cultivated spinach was safe for users.

Influence of the Kilning Conditions on Enzymatic Activity of Rice (Oryza sativa) Malt

Nguyen, Thach Minh,Nguyen, Xich Lien,Hoang, Kim Anh,Lee, Soo The Korean Society of Applied Science and Technolo 2009 한국응용과학기술학회지 Vol.26 No.1

This study investigated the effect of kilning condfition on the diastatic power and activities of protease, $\alpha$-amylase, and $\beta$-amylase in rice malt. Common rice (Oryza sativa) was steeped at $30^{\circ}C$ for 50 h, germinated at $30^{\circ}C$ for 7 days, and kilned at $50^{\circ}C$ for 24 h. The moisture content and enzymatic activities were determined under various kilning times. As a result, the moisture content was reduced from 42.1 % to 3.9% after 24 h of kilning at $50^{\circ}C$. The protease activity of rice malt showed lower value than that of barley malt. All enzymatic activities were decreased during the kilning stage. Results indicated that after prolonged kilning at $50^{\circ}C$, the inactivation of hydrolytic enzymes might be occurred. Even though the amylolytic activity of malted rice showed low value, the rice malt shows the potential characteristics as ingredient for the brewing and cereal industries.

Optimization of Rice (Oryza Sativa) Malting Process by Second-Order Experimental Design

Nguyen, Thach Minh,Nguyen, Xich Lien,Hoang, Kim Anh,Lee, Soo The Korean Society of Applied Science and Technolo 2008 한국응용과학기술학회지 Vol.25 No.3

The malting process of rice (OM4080 variety from Mekong Delta Rice Research Institute) was studied under pilot condition plan by means of the second-order experimental design. Processing parameters, such as the steeping time (0-60 hrs), steeping temperature ($5-45^{\circ}C$), germination time (0-8 days), germination temperature ($5-45^{\circ}C$) and gibberellin concentration (0-2 mg/kg) were investigated. As a result, all germination conditions, especially germination time, germination temperature, and gibberellin concentration had a significant effect on the malting loss, amylase activity and starch content. The protein content was not clearly affected by any conditions. The optimum conditions for malting process (with highest amylase activity) were as follows: 30 hrs of steeping time, $30-35^{\circ}C$ of steeping temperature, 5-5.5 days of germination time, $25^{\circ}C$ of germination temperature, and 1.5 mg/kg of giberrellin concentration.

Topical delivery of dexamethasone acetate from hydrogel containing nanostructured liquid carriers and the drug

Nguyen-Thach Tung,Vu-Thu Huyen,지상철 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.11

The potential of hydrogel containing nanostructuredlipid carriers (NLC) to enhance the skin permeationrate and skin deposition of dexamethasone acetate(DEA) was investigated. The particle size of obtainedNLCs was around 224.4 nm. NLCs had core–shell structureand DEA existed in amorphous state in NLCs. Thepermeation rate of DEA through excised mouse skins fromhydrogel containing DEA–NLC (DEA–NLC-hydrogel)was 7.3 times higher than DEA-ointment. The skin depositionof DEA from DEA–NLC-hydrogel increased 3.8folds compared to that from solution of DEA in hydrogel(DEA-hydrogel).

Korean Red Ginseng inhibits apoptosis in neuroblastoma cells via estrogen receptor ${\beta}$-mediated phosphatidylinositol-3 kinase/Akt signaling

Nguyen, Cuong Thach,Luong, Truc Thanh,Kim, Gyu-Lee,Pyo, Suhkneung,Rhee, Dong-Kwon The Korean Society of Ginseng 2015 Journal of Ginseng Research Vol.39 No.1

Background: Ginseng has been shown to exert antistress effects both in vitro and in vivo. However, the effects of ginseng on stress in brain cells are not well understood. This study investigated how Korean Red Ginseng (KRG) controls hydrogen peroxide-induced apoptosis via regulation of phosphatidylinositol-3 kinase (PI3K)/Akt and estrogen receptor (ER)-${\beta}$ signaling. Methods: Human neuroblastoma SK-N-SH cells were pretreated with KRG and subsequently exposed to $H_2O_2$. The ability of KRG to inhibit oxidative stress-induced apoptosis was assessed in MTT cytotoxicity assays. Apoptotic protein expression was examined byWestern blot analysis. The roles of ER-${\beta}$, PI3K, and p-Akt signaling in KRG regulation of apoptosis were studied using small interfering RNAs and/or target antagonists. Results: Pretreating SK-N-SH cells with KRG decreased expression of the proapoptotic proteins p-p53 and caspase-3, but increased expression of the antiapoptotic protein BCL2. KRG pretreatment was also associated with increased ER-${\beta}$, PI3K, and p-Akt expression. Conversely, ER-${\beta}$ inhibition with small interfering RNA or inhibitor treatment increased p-p53 and caspase-3 levels, but decreased BCL2, PI3K, and p-Akt expression. Moreover, inhibition of PI3K/Akt signaling diminished p-p53 and caspase-3 levels, but increased BCL2 expression. Conclusion: Collectively, the data indicate that KRG represses oxidative stress-induced apoptosis by enhancing PI3K/Akt signaling via upregulation of ER-${\beta}$ expression.

A two-step design of experiments approach to investigate the simultaneous effects of ion-pairing and chemical enhancers to improve the permeability of lornoxicam in a topical hydrogel patch

Nguyen Huu-Manh,Duong The-Khang,Nguyen Van-Khuyen,Nguyen Thi-Khanh-Ly,Dong Thi-Hoang-Yen,Nguyen Canh-Hung,Tung Nguyen-Thach 한국약제학회 2024 Journal of Pharmaceutical Investigation Vol.54 No.2

Purpose A two-step experimental design was used to develop a lornoxicam (LOR)-loaded topical hydrogel patch. We specifically focused on the simultaneous effect of the ion pair formation agent (triethanolamine [TEA]) and the chemical enhancer (cremophor RH40 [RH40]) on flux and conducted physicochemical studies and skin physiology assessments to obtain further information. Methods Drug-in-adhesive patches were fabricated using a micrometer-adjustable film applicator. The applied Design of Experiments (DoE) approach consisted of the Fractional Factorial Resolution V + design and the Central Composite Face design established by the MODDE® 12.0 software. Molecular-level drug-excipient interactions were investigated using infrared (IR) and proton nuclear magnetic resonance (1H NMR) spectroscopy. The effects on skin physiological function was assessed using DermaLab Combo. Results DoE results revealed that TEA enhanced flux by 3.14-fold, whereas RH40 reduced it by 4.62-fold. The addition of RH40 resulted in the disappearance of the proton peak within the region of 12–13 ppm, suggesting competition for hydrogen bonding with LOR between TEA and RH40. The optimized formulation (4% TEA, 0% RH40, and 0.2% Al(OH)3) increased skin hydration by 6.20-fold. Opposing effects of TEA and RH40 on skin elasticity were observed. Conclusion Expected flux and adhesion strength for the optimized formulation were 7.18 μg·cm–2·h–1 and 11.79 mJ, respectively. Our understanding of the conflicting effects of TEA and RH40 has been advanced. The integrated use of the two-step DoE, physicochemical studies, and skin physiology assessments was proven to be effective in elucidating the simultaneous effects of different permeation-modifying strategies on patches, thus having substantial value for the successful execution of future research endeavors.