Duy Hieu Truong | Yeungnam University (original) (raw)

Papers by Duy Hieu Truong

In this investigation, a smart nanocarrier-loaded docetaxel, a microtubules disrupting agent and ... more In this investigation, a smart nanocarrier-loaded docetaxel, a microtubules disrupting agent and vorinostat, a histone deacetylase inhibitor was developed to achieve a synergistic anticancer effect. Dual drug-loaded lipid polymer hybrid nanoparticles were prepared, with easy fabrication and favorable properties including small size, narrow distribution and a high loading efficacy. The in vitro drug release conducted in phosphate-buffered saline, pH 7.4 and acetate-buffered saline, pH 5.5 media demonstrated the sustained, pH-dependent release profile. The nanoparticles were effectively taken up by cells, which ensured greater suppression of cell growth. The co-delivery of both drugs exhibited a synergistic effect on the induction of cancer cell apoptosis, resulting in greater inhibition of SCC-7, MCF-7, and MDA-MB-231 cancer cells by the drug-loaded carrier. These promising results may lead to clinical applications with enhanced docetaxel activity.

Acta Biomaterialia, 2019

The expression of Toll-like receptors (TLRs) on antigen presenting cells, especially dendritic ce... more 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. Statement of Significance Toll-like receptors (TLRs), which express on antigen presenting cells, such as dendritic cells and macro-phages, 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.

To date, hyperthermia and chemotherapy have been widely investigated in the field of anticancer n... more 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 chemo-therapy 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 syner-gistic effect of hyperthermia and chemotherapy. This review will discuss the underlying mechanisms of action of chemo-hyperthermia 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.

Immunotherapy holds tremendous promise for improving cancer treatment in which an appropriate sti... more Immunotherapy holds tremendous promise for improving cancer treatment in which an appropriate stimulator may naturally trigger the immune system to control cancer. Up-to-date, adoptive T-cell therapy has received two new FDA approvals that provide great hope for some cancer patient groups. Nevertheless, expense and safety-related issues require further study to obtain insight into targets for efficient immunotherapy. The development of material science was largely responsible for providing a promising horizon to strengthen immunoengineering. In this review, we focus on T-cell characteristics in the context of the immune system against cancer and discuss several approaches of exploiting engineered particles to manipulate the responses of T cells and the tumour microenvironment.

Crosstalk among immune cells has attracted considerable attention with the advent of immunotherap... more Crosstalk among immune cells has attracted considerable attention with the advent of immunotherapy as a novel therapeutic approach for challenging diseases, especially cancer, which is the leading cause of mortality worldwide. Dendritic cells—the key antigen-presenting cells—play a pivotal role in immunological response by presenting exogenous epitopes to T cells, which induces the self-defense mechanisms of the body. Furthermore, nanotechnology has provided promising ways for diagnosing and treating cancer in the last decade. The progress in nanoparticle drug carrier development, combined with enhanced understanding of the immune system, has enabled harnessing of anti-tumor immunity. This review focuses on the recent advances in nanotechnology that have improved the therapeutic efficacy of immunotherapies, with emphasis on dendritic cell physiology and its role in presenting antigens and eliciting therapeutic T cell response.

Daclatasvir, asunaprevir (ASV), and beclabuvir (BCV) are direct-acting antivirals (DAAs) for pati... more Daclatasvir, asunaprevir (ASV), and beclabuvir (BCV) are direct-acting antivirals (DAAs) for patients with hepatitis C virus genotype 1 infection. This systematic review and meta-analysis investigating the efficacy and safety of this three-drug combination in HCV genotype 1 infection. Eleven electronic search engines were searched for relevant publications. Studies were screened for eligibility and data was extracted. The outcomes were pooled as event rate and risk ratio (RR). The protocol was registered in PROSPERO (CRD42017054391). Among the included six studies, five studies were included for the meta-analysis (n = 1261). The three-drug combination showed a high response rate in naïve patients with sustained virologic response at week-12 posttreatment (SVR 12) rate = 95.7% (95%CI [93.8-97.1]) and no difference detected by adding ribavirin (RBV) (the pooled RR = 0.98, 95%CI [0.90-1.08], P = 0.70) or comparing with interferon-experienced patients (RR = 1.02, 95%CI [0.98-1.07], P = 0.31) regardless the genotype 1 subtypes or IL28B genotype. Treatment failure was minimal and showed no difference regarding the previous comparisons. Increasing the dose or the duration did not show a significant increase in the efficacy. In conclusion, this analysis showed high response rates in HCV genotype 1-infected patients treated with daclatasvir, ASV, and BCV irrespective of RBV use, prior interferon-based therapy, or restriction on non-cirrhotic patients, IL28B genotype, or baseline resistance-associated variants.

Ginsenoside Rh1 is one of major bioactive compounds extracted from red ginseng, which has been in... more Ginsenoside Rh1 is one of major bioactive compounds extracted from red ginseng, which has been increasingly used for enhancing cognition and physical health worldwide. The objective of this study was to review the pharmacological effects of ginsenoside Rh1 in a systematic manner. We performed searches on eight electronic databases including MEDLINE (Pubmed), Scopus, Google Scholar, POPLINE, Global Health Library, Virtual Health Library, the System for Information on Grey Literature in Europe, and the New York Academy of Medicine Grey Literature Report to select the original research publications reporting the biological and pharmacological effects of ginsenoside Rh1 from in vitro and in vivo studies regardless of publication language and study design. Upon applying the inclusion and exclusion criteria, we included a total of 57 studies for our systemic review. Ginsenoside Rh1 exhibited the potent characteristics of anti-inflammatory, antioxidant, immunomodulatory effects, and positive effects on the nervous system. The cytotoxic effects of ginsenoside Rh1 were dependent on different types of cell lines. Other pharmacological effects including estrogenic, enzymatic, anti-microorganism activities, and cardiovascular effects have been mentioned, but the results were considerably diverged. A higher quality of evidence on clinical trial studies is highly recommended to confirm the consistent efficacy of ginsenoside Rh1.

Introduction The efficacy of endothelin receptor antagonists (ERAs) in the management of Eisenmen... more Introduction The efficacy of endothelin receptor antagonists (ERAs) in the management of Eisenmenger syndrome (ES) remains controversial. The aim of this study is to systemically review the safety and effects of ERAs in improving the quality of life and basic cardiac functions of these patients. Methods Twelve databases were searched, including PubMed, Web of Science, Scopus, Virtual Health Library, World Health Organization (WHO) Global Health Library, Google Scholar, POPLINE, Systems for Information of Grey Literature in Europe, New York Academy of Medicine, ClinicalTrials.gov, metaRegister of Controlled Trials and the WHO International Clinical Trials Registry Platform, through August 2016. We included randomized clinical trials addressing the effect of ERAs on cardiac functions in patients with ES. The quality of studies was assessed using the Cochrane Collaboration tool. Results We included two trials represented by four papers, of which three papers reported the efficacy of bosentan against placebo and one paper reported the results of a combination of bosentan and sildenafil versus placebo and bosentan. One trial showed a significant effect of bosentan treatment over placebo on indexed pulmonary vascular resistance and mean pulmonary artery pressure, but a nonsignificant increase in 6-min walk distance and a non-significant effect on systemic pulse oximetry. The other trial reported the safe but non-significant effect of combination therapy of bosentan and sildenafil compared with bosentan and placebo. Conclusions This study demonstrated safety and improved hemodynamic effects of bosentan in ES, with a Abdelrahman Elshafay and Duy Hieu Truong equally contributed to the work.

Nanofabrication of polymeric micelles through self-assembly of an ionic block copolymer and oppos... more 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 different 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 prolonged blood circulation. MTX-PCM improved the AUC all 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.

Purpose To investigate whether delivery of a histone deacetylase inhibitor, vorinostat (VOR), by ... more Purpose To investigate whether delivery of a histone deacetylase inhibitor, vorinostat (VOR), by using solid lipid nanoparticles (SLNs) enhanced its bioavailability and effects on multidrug-resistant cancer cells. Methods VOR-loaded SLNs (VOR-SLNs) were prepared by hot homogenization using an emulsification-sonication technique, and the formulation parameters were optimized. The cytotoxicity of the optimized formulation was evaluated in cancer cell lines (MCF-7, A549, and MDA-MB-231), and pharmacokinetic parameters were examined following oral and intravenous (IV) administration to rats. Results VOR-SLNs were spherical, with a narrowly distributed average size of ~100 nm, and were physically stable for 3 months. Drug release showed a typical bi-phasic pattern in vitro, and was independent of pH. VOR-SLNs were more cytotoxic than the free drug in both sensitive (MCF-7 and A549) and resistant (MDA-MB-231) cancer cells. Importantly, SLN formulations showed prominent cytotoxicity in MDA-MB-231 cells at low doses, suggesting an ability to effectively counter the P-glycoprotein-related drug efflux pumps. Pharmacokinetic studies clearly demonstrated that VOR-SLNs markedly improved VOR plasma circulation time and decreased its elimination rate constant. The areas under the VOR concentration-time curve produced by oral and IV administration of VOR-SLNs were significantly greater than those produced by free drug administration. These in vivo results clearly highlighted the remarkable potential of SLNs to augment the bioavailability of VOR. Conclusions VOR-SLNs successfully enhanced the oral bioavailabil-ity, circulation half-life, and chemotherapeutic potential of VOR.

Hyaluronic acid (HA)-decorated solid lipid nanoparticles (SLNs) were developed for tumor-targeted... more Hyaluronic acid (HA)-decorated solid lipid nanoparticles (SLNs) were developed for tumor-targeted delivery of vorinostat (VRS), a histone deacetylase inhibitor. HA, a naturally occurring polysaccharide, which specifically binds to the CD44 receptor, was coated on a cationic lipid core through electrostatic interaction. After the optimization process, HA-coated VRS-loaded SLNs (HA-VRS-SLNs) were spherical, core-shell nanoparticles, with small size (∼100 nm), negative charge (∼−9 mV), and narrow size distribution. In vitro release profile of HA-VRS-SLNs showed a typical bi-phasic pattern. In addition, the intracellular uptake of HA-VRS-SLNs was significantly enhanced in CD44 overexpressing cells, A549 and SCC-7 cells, but reduced when HA-VRS-SLNs were incubated with SCC-7 cells pretreated with HA or MCF-7 cells with low over-expressed CD44. Of particular importance, HA-VRS-SLNs were more cytotoxic than the free drug and VRS-SLNs in A549 and SCC-7 cells. In addition, HA shell provided longer blood circulation and reduced VRS clearance rate in rats, resulting in enhanced higher plasma concentration and bioavailability. These results clearly indicated the potential of the HA-functionalized lipid nanoparticle as a nano-sized drug formulation for chemotherapy.

Oh Kim (2014): Development of lipid nanoparticles for a histone deacetylases inhibitor as a promi... more Oh Kim (2014): Development of lipid nanoparticles for a histone deacetylases inhibitor as a promising anticancer therapeutic, Drug Delivery To link to this article: http://dx.

The aim of this study is to investigate the potential of nanostructured lipid carriers (NLCs) in ... more 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 (FEN-NLCs) 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 AUC t-∞ was fourfold higher, respectively, compared to the free FEN suspension. According to these results, FEN-NLC 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.

The objective of the current study was to enhance dissolution and oral bioavailability of the poo... more The objective of the current study was to enhance dissolution and oral bioavailability of the poorly water-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 method with SFN, Soluplus, and sodium lauryl sulfate (SLS) at various weight ratios in water. 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 < 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.

To improve the solubility and oral bioavailability of erlotinib, a poorly water-soluble anticance... more 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 Transcutol 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 (PDI) of the resultant emulsions. Then, the optimized formulation containing 5% Labrafil M2125CS, 65% Labrasol, and 30% Transcutol was spray dried with dextran or Aerosil® and characterized for surface morphology, crystallinity, and pharmacokinetics in rats. Powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) exhibited the amorphous form or molecular dispersion of erlotinib in the formulations. The pharmacokinetic parameters of the optimized formulations showed that the maximum concentration (C max) 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.

Drafts by Duy Hieu Truong

The objectives of this systematic review are to determine the efficacy and safety of the combinat... more The objectives of this systematic review are to determine the efficacy and safety of the combination of three drugs, daclatasvir, asunaprevir, and beclabuvir in treatment of chronic hepatitis C virus.

Ginseng, a traditional herb medicine, has gained increasing popularity in the world market due to... more Ginseng, a traditional herb medicine, has gained increasing popularity in the world market due to various medicinal properties, such as anticancer, anti-inflammatory, enhancing immune response and cognition, hepatoprotective effects and protection against neurological disorders. These effects are closely related to the presence of various bioactive compounds in which ginsenosides are the major components. There are more than 30 ginsenosides which can be classified into at least 4 types of ginsenosides in Ginseng. Among these, Ginsenoside Rh1, a protopanaxatriol derivative, has been found to have stimulating effects on the central nervous system such as anti-fatigue and antihypertensive effects, anabolic stimulation, enhance mental acuity and intellectual performance (8). In addition, many studies have shown that ginsenoside Rh1 has neuroprotective effects, potential antineoplastic effects and acts as an adjuvant therapy in chronic inflammatory diseases to dexamethasone. We aim to systematically review the pharmacological effects of bioactive ginsenoside Rh1 on both human and animal subjects from the literature.

Chronic Hepatitis B Virus infection (CHB) is a major health problem affecting 350 million patient... more Chronic Hepatitis B Virus infection (CHB) is a major health problem affecting 350 million patients yearly. It leads to 500,000 deaths from liver complications per year. Repeated Immune response against the virus may lead to fibrosis, cirrhosis and even hepatocellular carcinoma. Currently the main therapies used in the treatment of CHB are Interferon (IFN) and nucleoside analogues, but recently studies have been reporting evidence of combined vaccine and lamivudine (LAM) treatment with variable effects, this may be due to different timing of the vaccination, different types and doses of the vaccine, the duration of vaccine intervention and the population of the trials. We aim to review the literature systematically for evidence of the efficacy of the HBV vaccine alone or any combination in (CHB) patients and meta-analyze the data of RCTs conducted in this domain.

Pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) has been recen... more Pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) has been recently classified into four subtypes: Eisenmenger syndrome (ES), Left-to-right shunts, PAH with coincidental CHD and postoperative PAH. ES covers all large intra-and extracardiac defects which starts as left-to-right shunts and develops to severe pulmonary vascular resistance (PVR) and to reversal (right-to-left) or bidirectional shunting (1). ES is the most severe, irreversible form of PAH-CHD that has tremendous impacts on morbidity and mortality, significantly reduces the patient's' quality of life. Unfortunately, treatment options of patients with ES have been limited to heart-lung transplantation or supportive measures, of which the former is only appropriate for a small group of patients (2-4). Endothelin receptor antagonists (ERAs) belong to a class of oral pharmaceutical agents currently indicated for the treatment of certain types of PAH. Recently, some clinical trials using Bosentan, a dual ERA, in ES patients have shown improvements in cardiac functions and favorable safety profiles (5-9). However, the role of ERAs in the treatment of Eisenmenger syndrome has not been systematically studied yet. Therefore, the purpose of this study is to perform a systematic review and meta-analysis of randomized clinical trials regarding the effectiveness and safety of ERAs in the treatment of ES patients.

Acta Biomaterialia, 2019