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Yoon Tae Goo,1,* Cheol-Ki Sa,1,* Ji Yeh Choi,2 Min Song Kim,1 Chang Hyun Kim,1 Hyeon Kyun Kim,1 Young Wook Choi1 1College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea; 2Department of Psychology, York University, Toronto, Ontario, Canada*These authors contributed equally to this workCorrespondence: Young Wook ChoiCollege of Pharmacy, Chung-Ang University, 84 Heuksuk-Ro, Dongjak-Gu, Seoul, 06974, KoreaTel +82 2 820 5609Email ywchoi@cau.ac.krPurpose: To enhance the oral bioavailability of revaprazan (RVP), a novel solid, supersaturable micelle (SSuM) was developed.Methods: Surfactants and solid carriers were screened based on a solubility and a flowability test, respectively. Supersaturating agents, including Poloxamer 407 (P407), were screened. The SSuM was optimized using a Box-Behnken design with three independent variables, including Gelucire 44/14:Brij L4 (G44/BL4; X1) and the amounts of Florite PS-10 (FLO; X2) and Vivapur 105 (VP105; X3), and three response variables, ie, dissolution efficiency at 30 min (Y1), dissolution enhancing capacity (Y2), and Carr’s index (Y3). The solid state property was evaluated, and a dissolution test was conducted. RVP, Revanex®, solid micelle (P407-free from the composition of SSuM), and SSuM were orally administrated to rats (RVP 20 mg equivalent/kg) for in vivo pharmacokinetic study.Results: G44 and BL4 showed great solubility, with a critical micelle concentration range of 119.2– 333.0 μg/mL. P407 had an excellent supersaturating effect. FLO and VP105 were selected as solid carriers, with a critical solidifying ratio (g/mL) of 0.30 and 0.91, respectively. With optimized values of X1 (– 0.41), X2 (0.31), and X3 (– 0.78), RVP (200 mg)-containing SSuM consisting of G44 (253.8 mg), BL4 (106.2 mg), FLO (99.3 mg), VP105 (199.8 mg), and P407 (40 mg) was developed, resulting in Y1 (40.3%), Y2 (0.008), and Y3 (12.3%). RVP existed in an amorphous state in the optimized SSuM, and the SSuM formed a nanosized dispersion in the aqueous phase, with approximately 71.7% dissolution at 2 h. The optimized SSuM improved the relative bioavailability of RVP in rats by approximately 478%, 276%, and 161% compared to raw RVP, Revanex®, and solid micelle, respectively.Conclusion: The optimized SSuM has great potential for the development of solidified formulations of poorly water-soluble drugs with improved oral absorption.Keywords: revaprazan, supersaturation, solid micelle, Box-Behnken design, dissolution, oral bioavailability

Chang Hyun Kim,1,* Cheol-Ki Sa,1,* Min Su Goh,1 Eun Seok Lee,1 Tae Hoon Kang,1 Ho Yub Yoon,1 Gantumur Battogtokh,2 Young Tag Ko,2 Young Wook Choi1 1College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea; 2College of Pharmacy, Gachon University, Incheon, Republic of Korea *These authors contributed equally to this work Background: RIPL peptide (IPLVVPLRRRRRRRRC)-conjugated nanostructured lipid carriers (RIPL-NLCs) can facilitate selective drug delivery to hepsin (Hpn)-expressing cancer cells, but they exhibit low stability in the blood. Generally, biocompatible and nontoxic poly(ethylene glycol) surface modification (PEGylation) can enhance NLC stability, although this may impair drug delivery and NLC clearance. To attain RIPL-NLC steric stabilization without impairing function, pH-sensitive cleavable PEG (cPEG) was grafted onto RIPL-NLCs (cPEG-RIPL-NLCs).Methods: Various types of NLC formulations including RIPL-NLCs, PEG-RIPL-NLCs, and cPEG-RIPL-NLCs were prepared using the solvent emulsification–evaporation method and characterized for particle size, zeta potential (ZP), and cytotoxicity. The steric stabilization effect was evaluated by plasma protein adsorption and phagocytosis inhibition studies. pH-sensitive cleavage was investigated using the dialysis method under different pH conditions. Employing a fluorescent probe (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate [DiI]), in vitro drug delivery capacity of the cPEG-RIPL-NLCs under different pH conditions was also performed on Hpn-expressing SKOV3 cells and 3D-tumor spheroids.Results: All prepared NLCs showed homogenous dispersion (

Background: Aerobic exercise is an important ally in the fight against cardiovascular risk factors. However, the effects of high-intensity exercise on these factors are still poorly known., Objective: To compare the effects of aerobic and anaerobic exercise protocols on cardiac risk factors., Methods: 22 individuals with mean age of 40+/-8 years were distributed into the following groups: control (CO), endurance training (ET) and interval training (IT). The protocols lasted 12 weeks, three times a week, with intensities of 10% below and 20% above the anaerobic threshold (AnT). The following measurements were taken: total body mass (TBM), body mass index (BMI), waist circumference (WC), hip circumference (HC), and body composition, in addition to plasma concentrations of glucose (GLU), total cholesterol (CHO), and triglycerides (TG). Waist-hip ratio (WHR) and conicity index (C index) were also calculated., Results: The TBM, BMI, WC, GLU, and body composition variables showed significant changes in the ET and IT groups. CHO and HC values were significantly reduced in the ET group, whereas WHR showed a significant reduction in the IT group. AnT and C index in the IT group were significantly different in relation to ET., Conclusion: In view of the differences found in the results of the variables studied in relation to the training performed, we conclude that an exercise program that includes both high and low-intensity activities is more efficient to ensure the reduction of a greater number of cardiac risk variables.

The purpose of this study was to characterize aerobic, anaerobic, handgrip strength, and body fat content (BF) characteristics in paralympic rowers (ROW) in order to determine motor disabled rowers' fitness level and if specific motor disabilities could impair performance in this specific population. Upper body anaerobic threshold (LacT), peak (PK-AnP), mean (M-AnP), and lower (L-AnP) anaerobic power, peak anaerobic power to weight ratio (RelPk-AnP) and fatigue index (FI) were measured by the Wingate test (WinT). Handgrip strength was also measured and skinfold sum was used to estimate BF and were compared with a reference group of recreational disabled athletes (CON). LacT was significantly higher (p < 0.01) in ROW compared with CON. RelPk-AnP and BF were significantly different (p < 0.05) in ROW compared with CON as well. All other measured parameters did not significantly differ between ROW and CON. In most of cases, rowers have shown a relative low performance level, induced probably by specific disabilities.