• Title/Summary/Keyword: drug delivery time

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Large-scale Synthesis of Uniform-sized Nanoparticles for Multifunctional Medical Applications

  • Hyeon, Taeg-Hwan
    • Proceedings of the Korean Vacuum Society Conference
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    • 2011.02a
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    • pp.1-1
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    • 2011
  • We developed a new generalized synthetic procedure, called as "heat-up process," to produce uniform-sized nanocrystals of many transition metals and oxides without a size selection process. We were able to synthesize uniform magnetite nanocrystals as much as 1 kilogram-scale from the thermolysis of Fe-oleate complex. Clever combination of different nanoscale materials will lead to the development of multifunctional nano-biomedical platforms for simultaneous targeted delivery, fast diagnosis, and efficient therapy. In this presentation, I would like to present some of our group's recent results on the designed fabrication of multifunctional nanostructured materials based on uniform-sized magnetite nanoparticles and their medical applications. Uniform ultrasmall iron oxide nanoparticles of <3 nm were synthesized by thermal decomposition of iron-oleate complex in the presence of oleyl alcohol. These ultrasmall iron oxide nanoparticles exhibited good T1 contrast effect. In in vivo T1 weighted blood pool magnetic resonance imaging (MRI), iron oxide nanoparticles showed longer circulation time than commercial gadolinium complex, enabling high resolution imaging. We used 80 nm-sized ferrimagnetic iron oxide nanocrystals for T2 MRI contrast agent for tracking transplanted pancreatic islet cells and single-cell MR imaging. We reported on the fabrication of monodisperse magnetite nanoparticles immobilized with uniform pore-sized mesoporous silica spheres for simultaneous MRI, fluorescence imaging, and drug delivery. We synthesized hollow magnetite nanocapsules and used them for both the MRI contrast agent and magnetic guided drug delivery vehicle.

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Research on Thymopentin Loaded Oral N-Trimethyl Chitosan Nanoparticles

  • Yuan, Xiao-Jia;Zhang, Zhi-Rong;Song, Qing-Guo;He, Qin
    • Archives of Pharmacal Research
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    • v.29 no.9
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    • pp.795-799
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    • 2006
  • Peptides, although high efficacy and specificity in their physiological function, usually have low therapeutical activities due to their poor bioavailability when administrated orally. Nanoparticles have been regarded as a useful vector for targeted drug delivery system because they can protect drug from being degraded quickly and pass the gastrointestinal barriers. Here we described a novel oral N-trimethyl chitosan nanoparticles formulation containing thymopentin (Tp5-TMC-NP). N-trimethyl chitosan (TMC) was synthesized and then used to prepare Tp5-TMC-NP by ionotropic gelation. A three-factor, five-level CCD (Central Composite Design) design was used in the optimization procedure, with HPLC as the analyzing method. The resulting Tp5-TMC-NP had a regular spherical surface and a narrow particle size range with a mean diameter of 110.6 nm. The average entrapment efficiency was 78.8%. The lyophilized Tp5-TMC-NP formulation was stable in $4^{\circ}C\;or\;-20^{\circ}C$ after storage of 3 months without obvious changes in morphology, particle size, pH and entrapment ratio. The results of the flow cytometer determination showed that the ratio of $CD4^+/CD8^+$ of Wistar female rat given Tp5-TMC-NP (ig) was 2.59 time that of the group given Tp5 (ig).

Nanomedicine: Drug Delivery Systems and Nanoparticle Targeting (나노의학: 나노물질을 이용한 약물전달시스템과 나노입자의 표적화)

  • Youn, Hye-Won;Kang, Keon-Wook;Chung, June-Key;Lee, Dong-Soo
    • Nuclear Medicine and Molecular Imaging
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    • v.42 no.5
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    • pp.337-346
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    • 2008
  • Applications of nanotechnology in the medical field have provided the fundamentals of tremendous improvement in precise diagnosis and customized therapy. Recent advances in nanomedicine have led to establish a new concept of theragnosis, which utilizes nanomedicines as a therapeutic and diagnostic tool at the same time. The development of high affinity nanoparticles with large surface area and functional groups multiplies diagnostic and therapeutic capacities. Considering the specific conditions related to the disease of individual patient, customized therapy requires the identification of disease target at the cellular and molecular level for reducing side effects and enhancing therapeutic efficiency. Well-designed nanoparticles can minimize unnecessary exposure of cytotoxic drugs and maximize targeted localization of administrated drugs. This review will focus on major pharmaceutical nanomaterials and nanoparticles as key components of designing and surface engineering for targeted theragnostic drug development.

Controlled Release of Tamsulosin from Nanopore-Forming Granules (미세 다공성 과립을 이용한 탐스로신의 방출제어)

  • Seo, Seong-Mi;Lee, Hyun-Suk;Lee, Jae-Hwi;Lee, Ha-Young;Lee, Bong;Lee, Hai-Bang;Cho, Sun-Hang
    • Journal of Pharmaceutical Investigation
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    • v.36 no.1
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    • pp.39-44
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    • 2006
  • Tamsulosin or a salt thereof such as its hydrochloride salt has been known to have an adrenaline ${\alpha}$ receptor blocking action for urethra and prostate areas. It has been widely used as a drug which lowers the prostate pressure and improves urinary disturbance accompanied by prostate-grand enlargement, thus for the treatment of prostatic hyperplasia. To avoid dose-dependent side effects of tamsulosin upon oral administration, the development of sustained-release delivery system is essentially required, that can maintain therapeutic drug levels for a longer period of time. The aim of this study was therefore to formulate sustained-release tamsulosin granules and assess their formulation variables. We designed entric coated sustained-release tamsulosin granules for this purpose. Nano-pores in the outer controlled release membrane were needed in order to obtain initial tamsulosin release even in an acidic environment such as gastric region. In our sustained release osmotic granule system, hydroxypropylmethylcellulose in a drug-containing layer was used as a rate controller. The drug-containing granules were coated with hydroxypropylmethylcellulose phthalate (HPMCP) and Eudragit, along with glycerol triacetate as an aqueous nano-pore former. The release of tamsulosin depended heavily on the type of Eudragit such as RS, RL, NE 30D, used in the formulation of controlled release layer. These results obtained clearly suggest that the sustained-release oral delivery system for tamsulosin could be designed with satisfying drug release profile approved by the Korean Food and Drug Administration.

Development of Constant Delivery Micro Pump in a Variable Pressure Environment for Intrathecal Drug Administration System (레져버에 압력이 가해지는 환경에서의 미소 정량 토출 펌프의 개발)

  • Lee, Tae Gyeong;Lee, Cheol Su;Jung, Yu Seok;Park, Gyeong Geun
    • Journal of the Korean Society of Manufacturing Technology Engineers
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    • v.26 no.4
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    • pp.387-394
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    • 2017
  • This paper develops a pump system for patient with chronic pain or cancer. The pump module is consists of two micro-valve and membrane. The micro-valve is operated by a solenoid. With two solenoid valves which are connected via a drug transport line, the inlet and outlet are completely blocked. A silicon rubber membrane located between the two valves makes the flow-rate constant without any backflow. This pump module can control the flow-rate of drugs by controlling the time that the valves are opened and closed. The reservoir consists of a drug chamber and a gas chamber. As the gas chamber encloses the drug chamber, propellant gas which is injected into the gas chamber pressurizes the drug chamber regardless of volume of the drug chamber. To design the pump module, analysis a constant efficiency test, and accuracy test for the pump module were conducted.

Bio-Derived Poly(${\gamma}$-Glutamic Acid) Nanogels as Controlled Anticancer Drug Delivery Carriers

  • Bae, Hee Ho;Cho, Mi Young;Hong, Ji Hyeon;Poo, Haryoung;Sung, Moon-Hee;Lim, Yong Taik
    • Journal of Microbiology and Biotechnology
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    • v.22 no.12
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    • pp.1782-1789
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    • 2012
  • We have developed a novel type of polymer nanogel loaded with anticancer drug based on bio-derived poly(${\gamma}$-glutamic acid) (${\gamma}$-PGA). ${\gamma}$-PGA is a highly anionic polymer that is synthesized naturally by microbial species, most prominently in various bacilli, and has been shown to have excellent biocompatibility. Thiolated ${\gamma}$-PGA was synthesized by covalent coupling between the carboxyl groups of ${\gamma}$-PGA and the primary amine group of cysteamine. Doxorubicin (Dox)-loaded ${\gamma}$-PGA nanogels were fabricated using the following steps: (1) an ionic nanocomplex was formed between thiolated ${\gamma}$-PGA as the negative charge component, and Dox as the positive charge component; (2) addition of poly(ethylene glycol) (PEG) induced hydrogen-bond interactions between thiol groups of thiolated ${\gamma}$-PGA and hydroxyl groups of PEG, resulting in the nanocomplex; and (3) disulfide crosslinked ${\gamma}$-PGA nanogels were fabricated by ultrasonication. The average size and surface charge of Dox-loaded disulfide cross-linked ${\gamma}$-PGA nanogels in aqueous solution were $136.3{\pm}37.6$ nm and $-32.5{\pm}5.3$ mV, respectively. The loading amount of Dox was approximately 38.7 ${\mu}g$ per mg of ${\gamma}$-PGA nanogel. The Dox-loaded disulfide cross-linked ${\gamma}$-PGA nanogels showed controlled drug release behavior in the presence of reducing agents, glutathione (GSH) (1-10 mM). Through fluorescence microscopy and FACS, the cellular uptake of ${\gamma}$-PGA nanogels into breast cancer cells (MCF-7) was analyzed. The cytotoxic effect was evaluated using the MTT assay and was determined to be dependent on both the concentration and treatment time of ${\gamma}$-PGA nanogels. The bio-derived ${\gamma}$-PGA nanogels are expected to be a well-designed delivery carrier for controlled drug delivery applications.

Sequential anti-inflammatory and osteogenic effects of a dual drug delivery scaffold loaded with parthenolide and naringin in periodontitis

  • Rui Chen;Mengting Wang;Qiaoling Qi;Yanli Tang;Zhenzhao Guo;Shuai Wu;Qiyan Li
    • Journal of Periodontal and Implant Science
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    • v.53 no.1
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    • pp.20-37
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    • 2023
  • Purpose: Our pilot study showed that a 3-dimensional dual drug delivery scaffold (DDDS) loaded with Chinese herbs significantly increased the regenerated bone volume fraction. This study aimed to confirm the synergistic anti-inflammatory and osteogenic preclinical effects of this system. Methods: The targets and pathways of parthenolide and naringin were predicted. Three cell models were used to assess the anti-inflammatory effects of parthenolide and the osteogenic effects of naringin. First, the distance between the cementoenamel junction and alveolar bone crest (CEJ-ABC) and the bone mineral density (BMD) of surgical defects were measured in a rat model of periodontitis with periodontal fenestration defects. Additionally, the mRNA expression levels of matrix metallopeptidase 9 (MMP9) and alkaline phosphatase (ALP) were measured. Furthermore, the number of inflammatory cells and osteoclasts, as well as the protein expression levels of tumor necrosis factor-alpha (TNF-α) and levels of ALP were determined. Results: Target prediction suggested prostaglandin peroxidase synthase (PTGS2) as a potential target of parthenolide, while cytochrome P450 family 19 subfamily A1 (CYP19A1) and taste 2 receptor member 31 (TAS2R31) were potential targets of naringin. Parthenolide mainly targeted inflammation-related pathways, while naringin participated in steroid hormone synthesis and taste transduction. In vitro experiments revealed significant antiinflammatory effects of parthenolide on RAW264.7 cells, and significant osteogenic effects of naringin on bone marrow mesenchymal stem cells and MC3T3-E1 cells. DDDS loaded with parthenolide and naringin decreased the CEJ-ABC distance and increased BMD and ALP levels in a time-dependent manner. Inflammation was significantly alleviated after 14 days of DDDS treatment. Additionally, after 56 days, the DDDS group exhibited the highest BMD and ALP levels. Conclusions: DDDS loaded with parthenolide and naringin in a rat model achieved significant synergistic anti-inflammatory and osteogenic effects, providing powerful preclinical evidence.

[ μ ]-Injection Molding Process Analysis for In-Plane Microneedle (In-Plane형 마이크로니들의 미세사출공정해석)

  • Kang J. J.;Heo Y. M.;Jung T. S.;Lee S. H.
    • Transactions of Materials Processing
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    • v.14 no.6 s.78
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    • pp.491-495
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    • 2005
  • Micro injection molding analysis for microneedle fabrication was performed in the present study. The dimensions of width and thickness for in-plane microneedle are $600{\mu}m$, $500{\mu}m$, respectively. A delivery system based on guidelines for traditional injection molding was designed for four-cavities molding system. To investigate the effects of processing conditions in the mirconeedle fabrication, injection molding analysis using commercial code was performed. It was shown that the total injection time has a significant effect on the fabrication of in-plane microneedles.

Analysis of Micro Injection Molding Process for Polymeric Microneedle Fabrication (플라스틱 마이크로니들의 미세사출성형공정에 대한해석)

  • Lee S. H.;Kang J. J.;Heo Y. M.;Jung T. S.
    • Proceedings of the Korean Society for Technology of Plasticity Conference
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    • 2005.05a
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    • pp.55-59
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    • 2005
  • Micro injection molding analysis for microneedle fabrication was performed in the present study. The dimensions of width and thickness for microneedle are 600um, 500um, respectively. A delivery system based on guidelines for traditional injection molding was designed for four-cavities molding system. To investigate the effects of processing conditions in the mirconeedle fabrication, injection molding analysis using commercial code was performed. It was shown that the total injection time has a significant effect on the fabrication of microneedles.

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Preparation of Nanoparticles in Drug Delivery System Using Guar Derivatives and Dialysis Method

  • Na, Kun;Kim, Yu-Eun;Lee, Ki-Young
    • Journal of Microbiology and Biotechnology
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    • v.9 no.1
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    • pp.50-55
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    • 1999
  • To develop a new form of controlled release dosage for administering for indomethacin (IND), two formulations of IND-loaded nanoparticles were designed based on polysaccharide (guar) derivatives. Nanoparticles prepared by the dialysis method were characterized with respect to morphology, size distribution, drug content, and in vitro drug release. Morphological studies by scanning electron microscopy (SEM) indicated that guar acetate (GA) nanoparticles were spherical in shape and had a smooth surface. The particle size distributions of formulation I (40mg of GA) and formulation II (80mg of GA) were shown to be $250.78\pm185.13nm$ and $718\pm145.90nm$ in distilled water ($20$^{\circ}C$), respectively. The drug loading efficiencies of nanoparticles were approximately 26% and 31% for formulations I and II, respectively. The differential scanning calorimetry (DSC) results indicated that the IND was perfectly distributed within GA nanoparticles. We also found, from the X-ray diffractometry analysis, that a decrease in the degree of crystallinity of the drug occurred in the nanoparticles. No changes between the original IND and the released IND from GA nanoparticles were detected by FT-IR. Using guar acetate, it is possible to design nanoparticles which allow the controlled release of IND over an extended period of time.

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