• Title/Summary/Keyword: drug modification

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Layer-by-layer assembled polymeric thin films as prospective drug delivery carriers: design and applications

  • Park, Sohyeon;Han, Uiyoung;Choi, Daheui;Hong, Jinkee
    • Biomaterials Research
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    • v.22 no.4
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    • pp.290-302
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    • 2018
  • Background: The main purpose of drug delivery systems is to deliver the drugs at the appropriate concentration to the precise target site. Recently, the application of a thin film in the field of drug delivery has gained increasing interest because of its ability to safely load drugs and to release the drug in a controlled manner, which improves drug efficacy. Drug loading by the thin film can be done in various ways, depending on type of the drug, the area of exposure, and the purpose of drug delivery. Main text: This review summarizes the various methods used for preparing thin films with drugs via Layer-by-layer (LbL) assembly. Furthermore, additional functionalities of thin films using surface modification in drug delivery are briefly discussed. There are three types of methods for preparing a drug-carrying multilayered film using LbL assembly. First methods include approaches for direct loading of the drug into the pre-fabricated multilayer film. Second methods are preparing thin films using drugs as building blocks. Thirdly, the drugs are incorporated in the cargo so that the cargo itself can be used as the materials of the film. Conclusion: The appropriate designs of the drug-loaded film were produced in consideration of the release amounts and site of the desired drug. Furthermore, additional surface modification using the LbL technique enabled the preparation of effective drug delivery carriers with improved targeting effect. Therefore, the multilayer thin films fabricated by the LbL technique are a promising candidate for an ideal drug delivery system and the development possibilities of this technology are infinite.

Oxidative Stress, Nrf2, and Epigenetic Modification Contribute to Anticancer Drug Resistance

  • Kang, Kyoung Ah;Hyun, Jin Won
    • Toxicological Research
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    • v.33 no.1
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    • pp.1-5
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    • 2017
  • Nuclear factor E2-related factor 2 (Nrf2), a transcription factor, controls the expression of genes encoding cytoprotective proteins, including antioxidant enzymes that combat oxidative and electrophilic stress to maintain redox homeostasis. However, recent studies demonstrated that, in cancer, aberrant activation of Nrf2 by epigenetic alterations promotes high expression of cytoprotective proteins, which can decrease the efficacy of anticancer drugs used for chemotherapy. In this review, we summarize recent findings regarding the relationship between oxidative stress, Nrf2, epigenetic modification, and anticancer drug resistance, which should aid in development of new strategies to improve chemotherapeutic efficacy.

The Relationship between Treatment Intention and Compliance in Newly Detected Hypertensive Patients (새로이 발견된 고혈압 환자들의 약물치료 및 생활양식 개선의도와 순응도와의 관계)

  • Bae, Sang-Soo;Lee, Sok-Goo
    • Journal of Preventive Medicine and Public Health
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    • v.34 no.4
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    • pp.417-426
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    • 2001
  • Objectives : To analyse the psychosocial factors associated with hypertension management(drug treatment and life style modification) of newly detected cases and to understand and assess their behavioral intention or behaviors. Methods : The survey area was a combined urban and rural area in Chungnam province, Korea, and the sampling method was cluster sampling. Study subjects included 541 newly detected cases of hypertension rated above stage 2 by JNC-VI from a community survey. The first survey was applied to 383 of these patients in order to discern their psychosocial characteristics. A follow-up survey was given to 345 persons with an 11-month interval following monthly telephone counseling concerning medication and life style modification by trained nurses. The final study subjects for analysis comprised 271 persons after excluding cases of incomplete data and change of address. Results : Among the 85(33.2%) new patients who had intended to undergo drug treatment, 30(35.3%) persons were treated with antihypertensive agent after 11 - month interval, while among the patients with no intention to receive treatment, only 36(21.1%) persons were treated. Hypertensive patients with a high intention score revealed a high score in life style modification compliance as well. Seventy three percent of the variance of behavioral intention to undergo hypertension management was explained by the patients attitude toward performing the behavior and subjective norm associated with behaviors related to the theory of reasoned action in structural modeling. Actual behaviors related positively with behavioral intention. The coefficient of determination was 0.255. Conclusion : Improving the compliance level of hypertensive patients in respect to drug treatment or life style modification requires a build up of positive behavioral intention, and caregivers must pay more attention to eventually converting behavioral intention to actual behaviors.

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Immune Activation by siRNA/Liposome Complexes in Mice Is Sequence- independent: Lack of a Role for Toll-like Receptor 3 Signaling

  • Kim, Ji Young;Choung, Sorim;Lee, Eun-Ju;Kim, Young Joo;Choi, Young-Chul
    • Molecules and Cells
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    • v.24 no.2
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    • pp.247-254
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    • 2007
  • Improvement in the pharmacokinetic properties of short interfering RNAs (siRNAs) is a prerequisite for the therapeutic application of RNA interference technology. When injected into mice as unmodified siRNAs complexed to DOTAP/Chol-based cationic liposomes, all 12 tested siRNA duplexes caused a strong induction of cytokines including interferon ${\alpha}$, indicating that the immune activation by siRNA duplexes is independent of sequence context. When modified by various combinations of 2'-OMe, 2'-F, and phosphorothioate substitutions, introduction of as little as three 2'-OMe substitutions into the sense strand was sufficient to suppress immune activation by siRNA duplexes, whereas the same modifications were much less efficient at inhibiting the immune response of single stranded siRNAs. It is unlikely that Toll-like receptor 3 (TLR3) signaling is involved in immune stimulation by siRNA/liposome complexes since potent immune activation by ds siRNAs was induced in TLR3 knockout mice. Together, our results indicate that chemical modification of siRNA provides an effective means to avoid unwanted immune activation by therapeutic siRNAs. This improvement in the in vivo properties of siRNAs should greatly facilitate successful development of siRNA therapeutics.

Regulation of post-translational modification in breast cancer treatment

  • Heo, Kyung-Sun
    • BMB Reports
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    • v.52 no.2
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    • pp.113-118
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    • 2019
  • The small ubiquitin-related modification molecule (SUMO), one of the post-translational modification molecules, is involved in a variety of cellular functions where it regulates protein activity and stability, transcription, and cell cycling. Modulation of protein SUMOylation or deSUMOylation modification has been associated with regulation of carcinogenesis in breast cancer. In the dynamic processes of SUMOylation and deSUMOylation in a variety of cancers, SUMO proteases (SENPs), reverse SUMOylation by isopeptidase activity and SENPs are mostly elevated, and are related to poor patient prognosis. Although underlying mechanisms have been suggested for how SENPs participate in breast cancer tumorigenesis, such as through regulation of target protein transactivation, cancer cell survival, cell cycle, or other post-translational modification-related machinery recruitment, the effect of SENP isoform-specific inhibitors on the progression of breast cancer have not been well evaluated. This review will introduce the functions of SENP1 and SENP2 and the underlying signaling pathways in breast cancer for use in discovery of new biomarkers for diagnosis or therapeutic targets for treatment.

On the Crystal Structure of a human Cell Division Cycle Controlling Protein Kinase(CDK2) and Structure-Based Drug Design

  • Kim, Sung-Hou-
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.04a
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    • pp.41-49
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    • 1994
  • The most common conventional method of discovering a drug involves a massive screening of a large number of compounds in chemical libraries or in the extracts from natural sources such as plants or microbial broths followed by chemical modification of one or more active compounds to improve their properties as a drug. When the three-dimensional structure of the target molecule for which the drug is searched is known the drug discovery process can be significantly simplified, This is especially true when the three-dimensional structure of a complex between the target and a lead compound is known. In this lecture our experience on the structure-based drug design for human CDK2(cyclin-dependent protein kinase 2) will be discussed with special emphasis on the strength and weakness of this approach of drug discovery. The regulation of the activity of CDK2 plays an important role in the cell proliferation of normal and cancer cells.

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Nanocellulose Applications for Drug Delivery: A Review

  • Lee, Seung-Hwan;Kim, Hyun-Ji;Kim, Jin-Chul
    • Journal of Forest and Environmental Science
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    • v.35 no.3
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    • pp.141-149
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    • 2019
  • Nanocellulose, which can exist as either cellulose nanocrystals or cellulose nanofibrils, has been used as a biomaterial for drug delivery owing to its non-immunogenicity, biocompatibility, high specific area, good mechanical properties, and variability for chemical modification. Various water-soluble drugs can be bound to and released from nanocelluloses through electrostatic interactions. The high specific surface area of nanocellulose allows for high specific drug loading. Additionally, a broad spectrum of drugs can bind to nanocellulose after facile chemical modifications of its surface. Controlled release can be achieved for various pharmaceuticals when the nanocellulose surface is chemically modified or physically formulated in an adequate manner. This review summarizes the potential applications of nanocelluloses in drug delivery according to published studies on drug delivery systems.

Characterization of Biocompatible Polyelectrolyte Complex Multilayer of Hyaluronic Acid and Poly-L-Lysine

  • Hahn, Sei-Kwang;Allan S. Hoffman
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.9 no.3
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    • pp.179-183
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    • 2004
  • A biocompatible polyelectrolyte complex multilayer (PECML) film consisting of poly-L-lysine (PLL) as a polycation and hyaluronic acid (HA) as a polyanion was developed to test its use for surface modification to prevent cell attachment and protein drug delivery. The formation of PECML through the electrostatic interaction of HA and PLL was confirmed by contact angle measurement, ESCA analysis, and HA content analysis. HA content increased rapidly up to 8 cycles for HA/PLL deposition and then slightly increased with an increasing number of deposition cycle. In vitro release of PLL in the PECML continued up to 4 days and ca. 25% of HA remained on the chitosan-coated cover glass after in vitro release test for 7 days. From the results, PECML of HA and PLL appeared to be stable for about 4 days. The surface modification of the chitosan-coated cover glass with PECML resulted in drastically reduced peripheral blood mononuclear cell (PBMC) attachment. Concerned with its use for protein drug delivery, we confirmed that bovine serum albumin (BSA) as a model protein could be incorporated into the PECML and its release might be triggered by the degradation of HA with hyaluronidase.