• Journal of Radiopharmaceuticals and Molecular Probes
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• v.7 no.1
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• pp.33-40
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• 2021

Recently, antibody-drug conjugates (ADCs) are used to deliver efficient cytotoxic payloads selectively in cancer cells. In the designing of an ADC, the antibody is connected to a toxic payload via a covalent linker, which helps to solubilizes the typical hydrophobic payload as well as stabilizes the linkage over circulation. The development of the linkers for the antibody drug conjugate is still in demand. Initially, the acid, disulfide, and cathepsin-sensitive ADCs attracted considerable attention for the delivery of a potent cytotoxic payload but suffer from instability in human and mouse plasma with a short half-life. In addition, It also suffer from a solubility issue that induces aggregation, which is the major problem in their development. ADCs associated with sulfatase and phosphatase cleavable linker are highly soluble due to the anionic nature of sulfate and phosphate groups. The ADCs also showed high stability in human and mouse plasma. Therefore, to overcome these limitations, sulfatase and phosphatase cleavable linkers were developed. This review focuses on the recently reported advantages of sulfatase and phosphatase cleavable linkers for ADCs.

• Genomics & Informatics
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• v.21 no.3
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• pp.42.1-42.23
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• 2023

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, one of the most deadly infections in humans. The emergence of multidrug-resistant and extensively drug-resistant Mtb strains presents a global challenge. Mtb has shown resistance to many frontline antibiotics, including rifampicin, kanamycin, isoniazid, and capreomycin. The only licensed vaccine, Bacille Calmette-Guerin, does not efficiently protect against adult pulmonary tuberculosis. Therefore, it is urgently necessary to develop new vaccines to prevent infections caused by these strains. We used a subtractive proteomics approach on 23 virulent Mtb strains and identified a conserved membrane protein (MmpL4, NP_214964.1) as both a potential drug target and vaccine candidate. MmpL4 is a non-homologous essential protein in the host and is involved in the pathogen-specific pathway. Furthermore, MmpL4 shows no homology with anti-targets and has limited homology to human gut microflora, potentially reducing the likelihood of adverse effects and cross-reactivity if therapeutics specific to this protein are developed. Subsequently, we constructed a highly soluble, safe, antigenic, and stable multi-subunit vaccine from the MmpL4 protein using immunoinformatics. Molecular dynamics simulations revealed the stability of the vaccine-bound Tolllike receptor-4 complex on a nanosecond scale, and immune simulations indicated strong primary and secondary immune responses in the host. Therefore, our study identifies a new target that could expedite the design of effective therapeutics, and the designed vaccine should be validated. Future directions include an extensive molecular interaction analysis, in silico cloning, wet-lab experiments, and evaluation and comparison of the designed candidate as both a DNA vaccine and protein vaccine.

• Steel and Composite Structures
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• v.49 no.5
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• pp.487-502
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• 2023

In the realm of nanotechnology, the nonlocal strain gradient theory takes center stage as it scrutinizes the behavior of spinning cantilever nanobeams and nanotubes, pivotal components supporting various mechanical movements in sport structures. The dynamics of these structures have sparked debates within the scientific community, with some contending that nonlocal cantilever models fail to predict dynamic softening, while others propose that they can indeed exhibit stiffness softening characteristics. To address these disparities, this paper investigates the dynamic response of a nonlocal cantilever cylindrical beam under the influence of external discontinuous dynamic loads. The study employs four distinct models: the Euler-Bernoulli beam model, Timoshenko beam model, higher-order beam model, and a novel higher-order tube model. These models account for the effects of functionally graded materials (FGMs) in the radial tube direction, giving rise to nanotubes with varying properties. The Hamilton principle is employed to formulate the governing differential equations and precise boundary conditions. These equations are subsequently solved using the generalized differential quadrature element technique (GDQEM). This research not only advances our understanding of the dynamic behavior of nanotubes but also reveals the intriguing phenomena of both hardening and softening in the nonlocal parameter within cantilever nanostructures. Moreover, the findings hold promise for practical applications, including drug delivery, where the controlled vibrations of nanotubes can enhance the precision and efficiency of medication transport within the human body. By exploring the multifaceted characteristics of nanotubes, this study not only contributes to the design and manufacturing of rotating nanostructures but also offers insights into their potential role in revolutionizing drug delivery systems.

• Korea Journal of Hospital Management
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• v.8 no.3
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• pp.118-142
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• 2003

This study is aimed at evaluating the financial structure of hospitals before and after the separation of prescription and drug dispensing policy started to be implemented in July 2000 and at making a suitable hospital managerial strategy through the verification of the factors which have effect on their profitability. This study investigated the hospitals which have passed the accredition review to be designated as a accredited training hospital each year for three years from 1999 to 2001. Those hospitals were selected from members of the Korea Hospital Association. 106 hospitals were targeted for analysis except for the hospitals whose financial statements and managerial performance were not reported faithfully. The financial indicators used in this study were stability indicators(liability to total assets, ratio of debt to fund balance, fixed ratio), liquidity indicators(current ratio, quick ratio), activity indicators(total assets turnover, fixed assets turnover), profitability indicators(net profit to total assets, net profit to net worth, operating margin), and operating expenses to patient revenues indicators(drug and supplies costs/payroll/overhead expenses). The result of this study are as follows: First, the analysis of the increase of loss-making hospitals before and after. The separation of prescription and drug dispensing policy shows that the number of loss-making hospitals increase after the separation(22.6% before the separation; 31.1% after the separation). However, there was no significant statistical difference. Second, the analysis of operating expenses to patient revenues indicators showed that the ratio of drug and supplies cost became lower in all hospitals but the ratio of payroll/overhead expenses became higher. Additionally, the factor which have the greatest effect on profitability was operating expenses to patient revenues indicators (drug and supplies costs/payroll/overhead expenses). Third, the analysis of managerial performance by four types of loss-loss, loss-profit, profit-loss and profit-profit compared the results before the separation with those after the separation revealed as follows : Reliance on liability to total assets became higher in the profit-loss type($56.2%{\rightarrow}66.4%$), lower in the loss-profit type($82.7%{\rightarrow}74.5%$). Total assets turnover became higher in the profit-profit type($1.3{\rightarrow}1.5$), but lower in the loss-profit type($0.8{\rightarrow}0.7$). Operating margin decreased to minus 5.9% from 4.3% in the profit-loss type, but increased to 7.2% from minus 7.8% in the loss-profit type. Forth, operating expenses to revenues indicators showed that the increase of payroll was the biggest in the profit-loss type($39.2%{\rightarrow}49.9%$) and that overhead cost decreased in the loss-profit type but that rather increased in other types.

• Polymer(Korea)
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• v.34 no.3
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• pp.274-281
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• 2010

In this study, PEG-PLA(or PLGA) amphiphilic di-block copolymers were synthesized by ring opening polymerization of D,L-lactide(or glycolide) and applied to polymeric micelle system for solubilization of a rosiglitazone as diabetes drug. The drug could be efficiently loaded into the polymer micelle by solid dispersion technique, and the drug-loaded micelles were characterized and evaluated as a drug delivery carrier by fluorescence spectrometer, DSC, and DLS measurements. The colloidal stability of drug loaded micelles in aqueous media could be enhanced by addition of 2-hydroxy-N-picolylnitinamide as a hydrotropic agent. The polymer micelles also showed biocompatible and nontoxic properties in vitro cell viability using MTT assay, and the drug loaded micelles were observed to be more effective than free drug for decreasing glucose in blood of rats.

• Journal of Food Hygiene and Safety
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• v.36 no.3
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• pp.220-227
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• 2021

Fluoroimide is a fungicide and is also used as a pesticide for persimmons and potatoes. The established fluoroimide pesticide analysis method takes a long time to perform and uses benzene, a carcinogen. In addition, a lower limit of quantification is required due to enforcement of the Positive List System. Therefore, this study aimed to improve the analysis method for residual fluoroimide to resolve the problems associated with the current method. The analytical method was improved with reference to the increased stability of fluoroimide under acidic conditions. Fluoroimide was extracted under acidic conditions by hydrogen chloride (4 N) and acetic acid. MgSO₄ and NaCl were used with acetonitrile. C₁₈ (octadecylsilane) 500 mg and graphitized carbon black 40 mg were used in the purification process. The experiment was conducted with agricultural products (hulled rice, potato, soybean, mandarin, green pepper), and liquid chromatograph-tandem mass spectrometry was used for the instrumental analysis. Recovery of fluoroimide was 85.7-106.9% with relative standard deviations (RSDs) of less than 15.6%. This study reports an improved method for the analysis of fluoroimide that might contribute to safety by substituting the use of benzene, a harmful solvent. Furthermore, the use of QuEChERS increased the efficiency of the improved method. Finally, this research confirmed the precise limit of quantification and these results could be used to improve the analysis of other residual pesticides in agricultural products.

• Journal of Pharmaceutical Investigation
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• v.41 no.2
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• pp.75-82
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• 2011

LB71350 is an HIV protease inhibitor with poor aqueous solubility and extensive first pass effect. The purpose of the present study was to test the feasibility of solid dosage form of LB71350 with improved bioavailability utilizing solid dispersion. Three different compositions with varying ratio of (LB71350: Gelucire 44/14: Tween 20) were studied. Capsule filling of these solid dispersion compositions was tested using a semi-automatic capsule filling system. Oral bioavailability in dog was tested. Chemical and physical stability at 4, 25 and $40^{\circ}C$ was monitored by HPLC assay, dissolution test, powder XRD and microscopy. The capsule filling system yielded uniform products of drug loading up to 10%. Oral bioavailability in dog was improved compared to the aqueous suspension of crystalline LB71350. Capsules were chemically stable for up to 6 months at $40^{\circ}C$. However, there were temperature and composition dependent physical changes. Decrease in dissolution rates after storage at $40^{\circ}C$ was due to the polymorphic change. In conclusion, manufacturing process, bioavailability, and physico-chemical stability have been considered to propose a solid dispersion capsule formulation for the HIV protease inhibitor with poor physico-chemical properties. A new less soluble crystalline form identified during the physical stability test warrants further study.

• Herbal Formula Science
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• v.24 no.2
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• pp.71-79
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• 2016

Objectives : To verify the equivalence between Atractylodis Rhizoma Alba herbal prescription(HP-ARA) and Atractylodis Rhizoma Alba herbal sub stance(HS-ARA). Methods : Safety tests by microbial regulation and heavy metal analysis (total heavy metal, Pb, As) and a stability test by long term shelf test for HP-ARA according to notification of the Ministry of Food and Drug Safety were carried out. Then, multi component profile of HP-ARA and HS -ARA were analyzed by HPLC. Results : The safety and stability of HP-ARA confirmed by several tests. Correlation coefficient of equivalence of HP-ARA and ARA-HS showed 0.992. Conclusion : Based on this result of equivalence between HP-ARA and HS-ARA, HP-ARA can substitute HS-ARA used to make herbal medicines (herbal decoction, pills and powder).

• Journal of Pharmaceutical Investigation
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• v.36 no.1
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• pp.11-17
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• 2006

The objective of this study was to confirm the effect of the type of dissolution media and paddle speed on nifedipine (ND) release profile from osmotic granule and the storage stability. Osmotic granule was manufactured by fluidized bed coating method. At each coating step, morphology of osmotic granule was differed. The size of osmotic granule was $750\;{\mu}m$ at 3 wt% membrane thickness. ND release was changed in diverse dissolution media, paddle speed. ND release is governed by not only osmotic pressure but diffusion from osmotic granule. ND release from osmotic granule decreased as storage period increased. These may be caused by liquid excipient which has low molecular weight. Storage stability of osmotic granule could be improved by removing liquid excipient from semipermeable membrane.

• Bulletin of the Korean Chemical Society
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• v.28 no.1
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• pp.99-102
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• 2007

To prepare freeze-dried ascorbyl palmitate (AsP)-containing liposome which can protect the drug from moisture attack and be used instantly by mixing with water for anti-aging and skin whitening therapy, AsP was encapsulated into liposomes and freeze-dried with trehalose. The freeze-dried liposome formulations were characterized by measuring water contents, particle size, time required for complete reconstitution. With the freeze-dried liposomes, we performed the stability test under accelerated conditions, skin permeation and localization test. The measurement of the time to perfect reconstitution showed that the freeze-dried liposomes can be changed to their initial state rapidly and short term stability test of AsP in reconstituted liposomes under accelerated conditions confirmed that the stability of AsP was considerably enhanced as compared to freshly prepared liposomes. The skin permeation and localization properties of AsP in reconstituted liposomes were not significantly different, indicating that the liposomal structures were maintained before and after freezedrying. In conclusion, the freeze-drying method provided a possible way to overcome the instability issue of AsP induced by the moisture and reproduced similar skin permeation and localization properties as shown by freshly prepared liposomes.