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( Duy Hieu Truong ),( Tuan Hiep Tran ),( Thiruganesh Ramasamy ),( Ju Yeon Choi ),( Han Gon Choi ),( Chul Soon Yong ),( Jong Oh Kim ) 영남대학교 약품개발연구소 2015 영남대학교 약품개발연구소 연구업적집 Vol.25 No.-
The objective of the current study was to enhance dissolution and oral bioavailability of the poorlywater-soluble drug, sorafenib (SFN), by solid dispersion (SD) technique using a novel amphiphilic copolymer, polyvinyl caprolactam. polyvinyl acetate.polyethyleneglycol graft copolymer (Soluplus®). The SD formulations were prepared by the spray drying methodwith SFN, Soluplus, and sodiumlauryl sulfate (SLS) at variousweight ratios inwater. The optimized SD formulation, which showed the highest dissolution rate in distilled water, was further characterized for surface morphology, crystallinity, dissolution in pH 1.2, pH 4.0, and pH 6.8, and pharmacokinetics in rats. Powder X-ray diffraction and differential scanning calorimetry revealed the amorphous form of SFN in the formulation. In addition, at the oral dosage of 20 mg/kg SFN, the SD formulation showed increased Cmax and AUC0.48h by 1.5- and 1.8-fold, compared to those of SFN powder, respectively (p b 0.05). These findings suggest that the preparation of SFN-loaded SD using Soluplus could be a promising strategy for improvement of oral bioavailability of SFN. ⓒ 2015 Elsevier B.V. All rights reserved.
( Duy Hieu Truong ),( Tuan Hiep Tran ),( Thiruganesh Ramasamy ),( Ju Yeon Choi ),( Hee Hyun Lee ),( Cheol Moon ),( Han Gon Choi ),( Chul Soon Yong ),( Jong Oh Kim ) 영남대학교 약품개발연구소 2016 영남대학교 약품개발연구소 연구업적집 Vol.26 No.-
To improve the solubility and oral bioavailability of erlotinib, a poorly water-soluble anticancer drug, solid self-emulsifying drug delivery system (SEDDS) was developed using solid inert carriers such as dextran 40 and Aerosil® 200 (colloidal silica). The preliminary solubility of erlotinib in various oils, surfactants, and co-surfactants was determined. Labrafil M2125CS, Labrasol, and Trunscutol HP were chosen as the oil, surfactant, and co-surfactant, respectively, for preparation of the SEDDS formulations. The ternary phase diagram was evaluated to show the self-emulsifying area. The formulations were optimized using the droplet size and polydispersity index (POI) of the resultant emulsions. Then, the optim.ized formulation containing 5% Labrafil M2125CS, 65% Labrasol, and 30% Transcutol was spray dried with dextran or Aerosil® and characterized for surface morphology, crystallinity, and pharmacoki-netics in rats. Powder X-ray diffraction (PXRO) and differential scanning calorimetry (OSC) exhibited the amorphous form or molecular dispersion of erlotinib in the formulations. The pharmacokinetic parame-ters of the optimized formulations showed that the maximum concentration (C<sub>max</sub>) and area under the curve (AUC) of erlotinib were significantly increased, compared to erlotinib powder (p<0.05). Thus, this SEDDS could be a promising method for enhancing the oral bioavailability of erlotinib.
Combined hyperthermia and chemotherapy as a synergistic anticancer treatment
Jong Oh Kim,Duy Hieu Truong,Tuan Hiep Tran,Dai Cao Phung,Hanh Thuy Nguyen,Thi Thu Phuong Tran,Sung Giu Jin,Chul Soon Yong 한국약제학회 2019 Journal of Pharmaceutical Investigation Vol.49 No.5
To date, hyperthermia and chemotherapy have been widely investigated in the field of anticancer nanomedicine. However, in many cases, the efficacy of monotherapies have been limited owing to the heterogeneity of cancers and the acquired drug resistance. Noteworthy, hyperthermia has been demonstrated to offer numerous advantages when integrated with chemotherapy in nanoplatforms, namely increased accumulation of drugs in tumor site, enhanced cellular uptake, inhibition of DNA repair, and accelerated drug cytotoxicity against cancer cells. These evidences suggest a promising anticancer synergistic effect of hyperthermia and chemotherapy. This review will discuss the underlying mechanisms of action of chemohyperthermia combination therapy, and especially the strategies of design of advanced nanocarriers to effectively co-deliver hyperthermia and chemotherapeutic agents to the tumor based on various types of materials.
Hong Thi Bich Truong,Hiep Nghia Bui,Hieu Trung Nguyen,Thanh-Luu Pham,Duy Ngoc Nguyen,Yuan-Shing Perng,Linh Thi My Lam,Thi-Dieu-Hien Vo,Van-Truc Nguyen,Ha Manh Bui 한국화학공학회 2022 Korean Journal of Chemical Engineering Vol.39 No.4
Electron-beam (EB) irradiation was employed to degrade enrofloxacin (ENR) in an aqueous solution. Thealgal growth inhibition test revealed that ENR exhibited low toxicity against the cyanobacterium Arthrospira sp., with anEC50-96 h value of 5.17mg/L. The Taguchi design also involved finding the best optimum for ENR treatment using EB. Results revealed that the high-efficiency removal of ENR in an aqueous solution was approximately 98.53% under theoptimum conditions of an absorbed dose of 5 kGy, a pH of 5.0, and an initial ENR concentration of 10 mg/L and anH2O2 concentration of 2mM. The ERR degradation under a couple of EB irradiation and H2O2 followed pseudo-firstorderkinetics, with an R2 of ~0.970. The major degradation pathways of ENR were suggested by density functional theory,natural bond orbital calculations, and liquid chromatography-tandem mass spectrometry (LC/MS/MS) analysis. Lifecycle assessment (LCA) was also performed to evaluate the impact of the EB on removing ENR; the industrial processwas designed based on laboratory tests aimed with the ReCiPe tool. The obtained results indicated that energy consumptionand H2O2 affect environmental impacts with order human health, ecology systems, and natural resource. The LCAalso proved that EB could be a green and efficient method for eliminating pharmaceutical contaminants in water.
Tran, Tuan Hiep,Tran, Thi Thu Phuong,Truong, Duy Hieu,Nguyen, Hanh Thuy,Pham, Tung Thanh,Yong, Chul Soon,Kim, Jong Oh Elsevier Science B.V. Amsterdam 2019 ACTA BIOMATERIALIA Vol. No.
<P><B>Abstract</B></P> <P>The expression of Toll-like receptors (TLRs) on antigen presenting cells, especially dendritic cells, offers several sensitive mediators to trigger an adaptive immune response, which potentially can be exploited to detect and eliminate pathogenic objects. Consequently, numerous agonists that target TLRs are being used clinically either alone or in combination with other therapies to strengthen the immune system in the battle against cancer. This review summarizes the roles of TLRs in tumor biology, and focuses on relevant TLR-dependent antitumor pathways and the conjugation of TLR agonists as adjuvants to nano- and micro-particles for boosting responses leading to cancer suppression and eradication.</P> <P><B>Statement of Significance</B></P> <P>Toll-like receptors (TLRs), which express on antigen presenting cells, such as dendritic cells and macrophages, play an important role in sensing pathogenic agents and inducing adaptive immunity. As a result, several TLR agonists have been investigating as therapeutic agents individually or in combination with other treatment modalities for cancer treatment through boosting the immune system. This review aims to focus on the roles of TLRs in cancer and TLR-dependent antitumor pathways as well as the use of different nano- or micro-particles bearing TLR agonists for tumor inhibition and elimination.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
( Tuan Hiep Tran ),( Duc Thanh Chu ),( Duy Hieu Truong ),( Jin Wook Tak ),( Jee Heon Jeong ),( Van Luong Hoang ),( Chul Soon Yong ),( Jong Oh Kim ) 영남대학교 약품개발연구소 2016 영남대학교 약품개발연구소 연구업적집 Vol.26 No.-
Background; Vorinostat (VRS), a histone deacetylases inhibitor, has significant cytotoxic potential in a large number of human cancer cell lines. Objective: To clarify its promising anticancer potential and to improve its drawback related to physical properties and in vivo performance of VRS. Methods: VRS was successfully incorporated into nanostructured lipid carriers (NLCs) by the hot microemulsion method using sonication following a homogenization technique. Results; After the optimization process, VRS-loaded NLCs (VRS-NLCs) were obtained as ideal quality nanoparticles with a spherical shape, small size (~150nm), negative charge (~-22 mV), and narrow size distribution. In addition, the high entrapment efficiency (~99%) and sustained drug release profile were recorded. Cytotoxicity study in three different cell lines (A549, MCF-7, and SCC-7) demonstrated higher cytotoxicity of VRS-NLCs than free drug. Finally, the AUC of VRS (118.16 ± 17.35μgh/mL) was enhanced ~4.4 times compared with that of free drug (27.03 ± 3.25μgh/mL). Conclusion: These results suggest the potential of NLCs as an oral delivery system for enhancement of cellular uptake, in vitro cytotoxicity in cancer cell lines and the oral bioavailability of VRS.
( Tuan Hiep Tran ),( Thiruganesh Ramasamy ),( Duy Hieu Truong ),( Han Gon Choi ),( Chul Soon Yong ),( Jong Oh Kim ) 영남대학교 약품개발연구소 2015 영남대학교 약품개발연구소 연구업적집 Vol.25 No.-
The aim of this study is to investigate the potential of nanostructured lipid carriers (NLCs) in improving the oral bioavailability of a lipid lowering agent, fenofibrate (FEN). FEN-loaded NLCs (FENNLCs) were prepared by hot homogenization followed by an ultrasonication method using Compritol 888 ATO as a solid lipid, Labrafil M 1944CS as a liquid lipid, and soya lecithin and Tween 80 as emulsifiers. NLCs were characterized in terms of particle size and zeta pote\ntial, surface morphology, encapsulation efficiency, and physical state properties. Bioavailability studies were carried out in rats by oral administration of FEN-NLC. NLCs exhibited a spherical shape with a small particle size (84.9±4.9 nm). The drug entrapment efficiency was 99% with a loading capacity of 9.93±0.01% (w/w). Biphasic drug release manner with a burst release initially, followed by prolonged release was depicted for in vitro drug release studies. After oral administration of the FEN-NLC, drug concentration in plasma and AUCt-∞ was fourfold higher, respectively, compared to the free FEN suspension. According to these results, FENNLC could be a potential delivery system for improvement of loading capacity and control of drug release, thus prolonging drug action time in the body and enhancing the bioavailability.
Tran, Tuan Hiep,Chu, Duc Thanh,Truong, Duy Hieu,Tak, Jin Wook,Jeong, Jee-Heon,Hoang, Van Luong,Yong, Chul Soon,Kim, Jong Oh Informa UK (Informa Healthcare) 2016 DRUG DELIVERY Vol.23 No.4
<P>Background: Vorinostat (VRS), a histone deacetylases inhibitor, has significant cytotoxic potential in a large number of human cancer cell lines. Objective: To clarify its promising anticancer potential and to improve its drawback related to physical properties and in vivo performance of VRS. Methods: VRS was successfully incorporated into nanostructured lipid carriers (NLCs) by the hot microemulsion method using sonication following a homogenization technique. Results: After the optimization process, VRS-loaded NLCs (VRS-NLCs) were obtained as ideal quality nanoparticles with a spherical shape, small size (similar to 150 nm), negative charge (similar to-22 mV), and narrow size distribution. In addition, the high entrapment efficiency (similar to 99%) and sustained drug release profile were recorded. Cytotoxicity study in three different cell lines (A549, MCF-7, and SCC-7) demonstrated higher cytotoxicity of VRS-NLCs than free drug. Finally, the AUC of VRS (118.16 +/- 17.35 mu gh/mL) was enhanced similar to 4.4 times compared with that of free drug (27.03 +/- 3.25 mu gh/mL). Conclusion: These results suggest the potential of NLCs as an oral delivery system for enhancement of cellular uptake, in vitro cytotoxicity in cancer cell lines and the oral bioavailability of VRS.</P>
( Thiruganesh Ramasamy ),( Bijay Kumar Poudel ),( Himabindu Ruttala ),( Ju Yeon Choi ),( Truong Duy Hieu ),( Kandasamy Umadevi ),( Yu Seok Youn ),( Han Gon Choi ),( Chul Soon Yong ),( Jong Oh Kim ) 영남대학교 약품개발연구소 2016 영남대학교 약품개발연구소 연구업적집 Vol.26 No.-
Nanofabrication of polymeric micelles through self-assembly of an ionic block copolymer and oppositely charged small molecules has recently emerged as a promising method of formulating delivery systems. The present study therefore aimed to investigate the interaction of cationic drugs doxorubicin (DOX) and mitoxantrone (MTX) with the anionic block polymer poly(ethylene oxide)-block-poly(acrylic acid) (PEO-b-PAA) and to study the influence of these interactions on the pharmacokinetic stability and anti-tumor potential of the formulated micelles in clinically relevant animal models. To this end, individual DOX and MTX-loaded polyelectrolyte complex micelles (PCM) were prepared, and their physicochemical properties and pH-responsive release profiles were studied, MTX-PCM and DOX-PCM exhibited a differ-ent release profile under all pH conditions tested. MTX-PCM exhibited a monophasic release profile with no initial burst, while DOX-PCM exhibited a biphasic release, DOX-PCM showed a higher cellular uptake than that shown by MTX-PCM in A-549 cancer cells. Furthermore, DOX-PCM induced higher apoptosis of cancer cells than that induced by MTX-PCM, Importantly, both MTX-PCM and DOX-PCM showed pro-longed blood circulation. MTX-PCM improved the AUC<sub>all</sub> of MTX 4-fold compared to a 3-fold increase by DOX-PCM for DOX, While a definite difference in blood circulation was observed between MTX-PCM and DOX-PCM in the pharmacokinetic study, both MTX-PCM and DOX-PCM suppressed tumor growth to the same level as the respective free drugs, indicating the potential of PEGylated polymeric micelles as effective delivery systems. Taken together, our results show that the nature of interactions of cationic drugs with the polyionic copolymer can have a tremendous influence on the biological performance of a delivery system.