Formulation and optimization of novel Valsartan SMEDDS using statistical experimental design

Poudel Bijay Kumar,Marasini Nirmal,CHOI Han-Gon,YONG Chul Soon,KIM Jong Oh 대한약학회 2012 大韓藥學會 總會 및 學術大會 Vol.2012 No.1

<i>In situ</i> fabrication of mesoporous silica-coated silver-gold hollow nanoshell for remotely controllable chemo-photothermal therapy via phase-change molecule as gatekeepers

Poudel, Bijay Kumar,Soe, Zar Chi,Ruttala, Hima Bindu,Gupta, Biki,Ramasamy, Thiruganesh,Thapa, Raj Kumar,Gautam, Milan,Ou, Wenquan,Nguyen, Hanh Thuy,Jeong, Jee-Heon,Jin, Sung Giu,Choi, Han-Gon,Yong, Ch Elsevier 2018 International journal of pharmaceutics Vol.548 No.1

<P><B>Abstract</B></P> <P>This study reports a new strategy for <I>in situ</I> fabrication of plasmonic hollow silver-gold nanoshell (with resonance tuned to NIR region) encased in the hollow mesoporous silica as an efficient platform to efficiently and precisely regulate the release of 5-fluorouracil (anticancer drug) for prostate cancer therapy and photothermal therapy. The mesopores were capped with thermosensitive phase-change material lauric acid, which allowed for remote, precise, and spatiotemporal control of drug release via external heating or photothermal heating of plasmonic silver-gold nanoshell via NIR laser irradiation. The system was nanometric, monodispersed, and showed negative surface charge. The nanocarrier showed better pH stability and thermodynamic stability compared to dense silica-coated gold nanoshells. The drug release could be triggered remotely by applying low powered continuous wave NIR laser (λ = 808 nm). The nanocarrier showed improved internalization by cancer cells, which was further enhanced by laser irradiation. High powered laser directly killed the cancer cells via photothermal effect in the region irradiated. Thus, this system fabricated by novel synthetic strategy provided efficient chemo- and phototherapy.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Direct fluorescent labeling for efficient biological assessment of inhalable particles

Poudel, Bijay Kumar,Park, Jae Hong,Lim, Jiseok,Byeon, Jeong Hoon Informa UK (TaylorFrancis) 2017 Nanotoxicology Vol.11 No.8

<P>Labeling of aerosol particles with a radioactive, magnetic, or optical tracer has been employed to confirm particle localization in cell compartments, which has provided useful evidence for correlating toxic effects of inhaled particles. However, labeling requires several physicochemical steps to identify functionalities of the inner or outer surfaces of particles, and moreover, these steps can cause changes in size, surface charge, and bioactivity of the particles, resulting in misinterpretations regarding their toxic effects. This study addresses this challenging issue with a goal of introducing an efficient strategy for constantly supplying labeled aerosol particles in a single-pass configuration without any pre- or post-physicochemical batch treatments of aerosol particles. Carbon black (CB, simulating combustion-generated soot) or calcium carbonate (CC, simulating brake-wear fragments) particles were constantly produced via spark ablation or bubble bursting, respectively. These minute particles were incorporated with fluorescein isothiocyanate-poly(ethylene glycol) 2-aminoethyl ether acetic acid solution at the orifice of a collison atomizer to fabricate hybrid droplets. The droplets successively entered a diffusion dryer containing 254-nm UV irradiation; therefore, the droplets were dynamically stiffened by UV to form fluorescent probes on particles during solvent extraction in the dryer. Particle size distributions, morphologies, and surface charges before and after labeling were measured to confirm fluorescence labeling without significant changes in the properties. In vitro assays, including confocal imaging, were conducted to confirm the feasibility of the labeling approach without inducing significant differences in bioactivity compared with untreated CB or CC particles.</P>

PEGylated thermosensitive lipid-coated hollow gold nanoshells for effective combinational chemo-photothermal therapy of pancreatic cancer

Poudel, Bijay Kumar,Gupta, Biki,Ramasamy, Thiruganesh,Thapa, Raj Kumar,Pathak, Shiva,Oh, Kyung Taek,Jeong, Jee-Heon,Choi, Han-Gon,Yong, Chul Soon,Kim, Jong Oh Elsevier 2017 Colloids and surfaces Biointerfaces Vol.160 No.-

<P><B>Abstract</B></P> <P>Pancreatic cancer has extremely poor prognosis with an 85% mortality rate that results from aggressive and asymptomatic growth, high metastatic potential, and rapid development of resistance to already ineffective chemotherapy. In this study, plasmonic hollow gold nanoshells (GNS) coated with PEGylated thermosensitive lipids were prepared as an efficient platform to ratiometrically co-deliver two drugs, bortezomib and gemcitabine (GNS-L/GB), for combinational chemotherapy and photothermal therapy of pancreatic cancer. Bortezomib was loaded within the lipid bilayers, while gemcitabine was loaded into the hydrophilic interior of the porous GNS via an ammonium sulfate-driven pH gradient method. Physicochemical characterizations and biological studies of GNS-L/GB were performed, with the latter using cytotoxicity assays, cellular uptake and apoptosis assays, live/dead assays, and western blot analysis of pancreatic cancer cell lines (MIA PaCa-2 and PANC-1). The nanoshells showed remotely controllable drug release when exposed to near-infrared laser for site-specific delivery. GNS-L/GB showed synergistic cytotoxicity and improved internalization by cancer cells. High-powered near-infrared continuous wave laser (λ=808nm) effectively killed cancer cells via the photothermal effect of GNS-L/GB, irrespective of cell type in a power density-, time-, and GNS dose-dependent manner. These results suggest that this method can provide a novel approach to achieve synergistic combinational chemotherapy and photothermal therapy, even with resistant pancreatic cancer.</P> <P><B>Highlights</B></P> <P> <UL> <LI> PEGylated thermosensitive lipid-coated hollow gold nanoshells (GNS-L) were prepared. </LI> <LI> GNS-L were co-loaded with hydrophilic gemcitabine and hydrophobic bortezomib. </LI> <LI> NIR irradiation induced drug release for remotely controlled site-specific delivery. </LI> <LI> GNS-L increased cellular uptake and apoptosis in pancreatic cancer cells. </LI> <LI> Direct photothermal killing of cancer cells was observed on NIR laser irradiation. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

A batch-by-batch free route for the continuous production of black phosphorus nanosheets for targeted combination cancer therapy

Poudel, Bijay Kumar,Hwang, Jungho,Ku, Sae Kwang,Kim, Jong Oh,Byeon, Jeong Hoon Nature Publishing Group 2018 NPG Asia Materials Vol.10 No.-

The Pharmacological Effects of Benachio-F^® on Rat Gastrointestinal Functions

Poudel, Bijay Kumar,Yu, Jae Young,Kwon, Yong Sam,Park, Hyoung Geun,Son, Miwon,Jun, Joon Ho,Kim, Jeong Ah,Kim, Jong Oh The Korean Society of Applied Pharmacology 2015 Biomolecules & Therapeutics(구 응용약물학회지) Vol.23 No.4

Functional dyspepsia (FD) is a prevalent idiopathic upper gastrointestinal (GI) disorder characterized by diverse symptomatology including epigastric pain or discomfort, postprandial fullness, and early satiety. Although its pathophysiological mechanisms have not yet been fully established, the available studies suggest that the etiology of FD is invariably multifactorial. Benachio-F$^{(R)}$ (BF) is a proprietary liquid formulation of 7 herbal extracts that has been proposed to address this multifactorial etiology using multi-drug phytotherapy. The pharmacological effects of BF, in comparison with those of two other herbal products (Whalmyungsu$^{(R)}$; WM and Iberogast$^{(R)}$; IB) were evaluated in rats. In a laparotomy-induced rat model of delayed GI transit, BF significantly accelerated the delayed gastric emptying caused by morphine, apomorphine, and cisplatin, and also significantly increased mean gastric transit, as compared to the control animals. BF markedly increased gastric accommodation in rats and produced higher gastric volume values than did the control treatment. The effects of BF were generally comparable or superior to those of WM and IB in these models. Furthermore, BF significantly stimulated biliary flow, as compared to the control treatment. These results indicated that BF might have great potential as an effective phytotherapeutic agent capable of reducing GI symptoms and increasing quality of life in FD patients.

On-Demand Gas-to-Liquid Process To Fabricate Thermoresponsive Antimicrobial Nanocomposites and Coatings

Poudel, Bijay Kumar,Park, Jae Hong,Byeon, Jeong Hoon American Chemical Society 2017 ACS APPLIED MATERIALS & INTERFACES Vol.9 No.18

<P>Antimicrobial material is emerging as a major component of the mitigation strategy against microbial growth on abiotic surfaces. In this work, a newly designed process is proposed to fabricate thermoresponsive antimicrobial nano composites (TANs) and coatings (TACs) as an on-demand system. Thermoresponsive polymer (TRP)-incorporated silver (Ag) nanocomposites with silica nanoparticles (SNPs) or carbon nanotubes (CNTs; Ag-SNP@TRP or Ag-CNT@TRP) were produced by a single-pass gas-to-liquid process. The SNPs or CNTs were first produced by spark ablation and successively injected for dispersal in a liquid cell containing polydimethylsiloxane, poly(N-isopropylacrylamide), and silver nitrate under ultrasound irradiation. Suspensions of Ag-SNP@TRP or Ag-CNT@TRP nanocomposites were then deposited on a touch screen panel (TSP) protection film via electrohydrodynamic spray to form transparent antibacterial coatings. Fundamental antibacterial activities of TANs were evaluated against Escherichia coli and Staphylococcus epidermidis. The TANs showed stronger antibacterial activities at the higher temperature for all testing conditions. Lower minimum inhibitory concentrations of AgSNP@TRP and Ag-CNT@TRP nanocomposites were required against the two bacteria at 37 C-circle compared to those at 27 C-circle. The TACs on display showed elevated antimicrobial activity when the panel was turned on (38.1 C-circle) compared with when the panel was turned off (23.8 C-circle). This work provides a utilizable concept to continuously fabricate TANs and TACs, and it specifically offers stimuli-sensitive control of antimicrobial activity on TSPs, including other frequently touched surfaces.</P>

Development of polmeric irinotecan nanoparticles using a novel lactone preservation strategy

( Bijay Kumar Poudel ),( Biki Gupta ),( Thiruganesh Ramasamy ),( Raj Kumar Thapa ),( Yu Seok Youn ),( Han Gon Choi ),( Chul Soon Yong ),( Jong Oh Kim ) 영남대학교 약품개발연구소 2016 영남대학교 약품개발연구소 연구업적집 Vol.26 No.-

Irinotecan (IRT) is an important part of the first- and second-line regimen for metastatic colorectal and some other cancers. However, IRT suffers the constraints of pH-dependent conversion of active lactone form to inactive carboxylate form, burst release owing to its aqueous solubility, short half-life and dose-dependent side effects. In this study, we developed polymeric nanoparticles (NPs) that not only deliver IRT to tumor sites, but also overcome its drawbacks by preserving active lactone conformation, prolonging the plasma circulation time, and by providing sustained release. IRT complex was rendered hydrophobic by ion-pairing with anions (docusate sodium, sodium lauryl sulfate, and sodium tripolyphosphate), and loaded in PEG-PLGA NPs via water/oil/water double emulsification method. The NPs were spherical, ~60 nm, monodispersed, and had shell-core morphology. They retained >80% lactone form for more than 1 month of storage and exhibited sustained release characteristics. In addition, sub -100 nm size of NPs offered elevated cellular internalization. Owing to the presence of hydrophilic PEG outer layer and drug-loaded hydrophobic PLGA core, NPs conferred excellent plasma stability and prolonged the retention time of lRT by more than l0-fold as compared to free IRT. Therefore, this system could provide an excellent platform for efficient and sustained delivery of IRT and similar labile drugs to the tumor site, while maintaining their chemical integrity.

Receptor-targeted, drug-loaded, functionalized graphene oxides for chemotherapy and photothermal therapy

( Raj Kumar Thapa ),( Ju Yeon Choi ),( Bijay Kumar Poudel ),( Han Gon Choi ),( Chul Soon Yong ),( Jong Oh Kim ) 영남대학교 약품개발연구소 2016 영남대학교 약품개발연구소 연구업적집 Vol.26 No.-

Cancer is one of the leading causes of death worldwide. Although different chemotherapeutic agents have been developed to treat cancers, their use can be limited by low cellular uptake, drug resistance, and side effects. Hence, targeted drug delivery systems are continually being developed in order to improve the efficacy of chemotherapeutic agents. The main aim of this study was to prepare folic acid (F A)-conjugated polyvinyl pyrrolidone-functionalized graphene oxides (GO) (FA-GO) for targeted delivery of sorafenib (SF). GO were prepared using a modified Hummer``s method and subsequently altered to prepare FA-GO and SF-loaded FA-GO (FA-GO/SF). Characterization of GO derivatives was done using ultraviolet/ visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, atomic force microscopy, zeta potential measurements, and determination of in vitro drug release. Hemo-lytic toxicity, in vitro cytotoxicity, cellular uptake, and apoptotic effects of FA-GO/SF were also investigated. The results revealed that GO was successfully synthesized and that further transformation to FA-GO improved the stability and SF drug-loading capacity. In addition, the enhanced SF release under acidic conditions suggested possible benefits for cancer treatment. Conjugation of FA within the FA-GO/SF delivery system enabled targeted delivery of SF to cancer cells expressing high levels of FA receptors, thus increasing the cellular uptake and apoptotic effects of SF. Furthermore, the photothermal effect achieved by exposure of GO to near-infrared irradiation enhanced the anticancer effects ofF A-GO/SF. Taken together, FA-GO/SF is a potential carrier for targeted delivery of chemotherapeutic agents in cancer.

Formulation, Characterization and Optimization of Valsartan Self-Microemulsifying Drug Delivery System Using Statistical Design of Experiment

( Bijay Kumar Poudel ),( Nirmal Marasini ),( Tuan Hiep Tran ),( Han Gon Choi ),( Chul Soon Yong ),( Jong Oh Kim ) 영남대학교 약품개발연구소 2013 영남대학교 약품개발연구소 연구업적집 Vol.23 No.0

The aim of the present research was to systematically investigate the main, interaction and the quadratic effects of formulation variables on the performance of self-microemulsifying drug delivery system (SMEDDS) of valsartan using design of experiment. A 17-run Box-Behnken design (BBD) with 3-factors and 3-levels, including 5 replicates at the centre point, was used for fitting a 2nd-order response surface. After the preliminary screening, Labrafil M 2125 CS as oil, Tween 20 as surfactant and Capryol 90 as co-surfactant were taken as independent variables. The dependent factors (responses) were particle size, polydispersity index (PDI), dissolution after 15 min and equilibrium solubility. Coefficients were estimated by regression analysis and the model adequacy was checked by an F-test and the determination coefficient (R(2)). All the responses were optimized simultaneously by using desirability function. Our results demonstrated marked main and interaction effects of independent factors on responses. The optimized formulation consisted of 26.8% (w/w) oil, 60.1% (w/w) surfactant and 13.1% (w/w) co-surfactant, and showed average micelle size of 90.7 nm and 0.246 PDI, 91.2% dissolution after 15 min and 226.7 mg/g equilibrium solubility. For the optimized formulation, predicted value and experimental value were in close agreement. After oral administration, the optimized formulation gave more than 2-fold higher area under curve (AUC) and about 6-fold higher C(max) in rats than valsartan powder (p<0.05). The BBD facilitated in the better understanding of inherent relationship of formulation variables with the responses and in the optimization of valsartan SMEDDS in relatively time and labor effective manner.