• Title/Summary/Keyword: Controlled Release

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Multilayered phospholipid polymer hydrogels for releasing cell growth factors

  • Choi, Jiyeon;Konno, Tomohiro;Ishihara, Kazuhiko
    • Biomaterials and Biomechanics in Bioengineering
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    • v.1 no.1
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    • pp.1-12
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    • 2014
  • Polymer multilayered hydrogels were prepared on a titanium alloy (Ti) substrate using a layer-by-layer (LBL) process to load a cell growth factor. Two water-soluble polymers were used to fabricate the multilayered hydrogels, a phospholipid polymer with both N, N-dimethylaminoethyl methacrylate (DMAEMA) units and 4-vinylphenylboronic acid (VPBA) units [poly(MPC-co-DMAEMA-co-VPBA) (PMDV)], and the polysaccharide alginate (ALG). PMDV interacted with ALG through a selective reaction between the VPBA units in PMDV and the hydroxyl groups in ALG and through electrostatic interactions between the DMAEMA units in PMDA and the anionic carboxyl groups in ALG. First, the Ti substrate was covered with photoreactive poly vinyl alcohol, and then the Ti alloy was alternately immersed in the respective polymer solutions to form the PMDV/ALG multilayered hydrogels. In this multilayered hydrogel, vascular endothelial growth factor (VEGF) was introduced in different layers during the LbL process under mild conditions. Release of VEGF from the multilayered hydrogels was dependent on the location; however, release continued for 2 weeks. Endothelial cells adhered to the hydrogel and proliferated, and these corresponded to the VEGF release profile from the hydrogel. We concluded that multilayered hydrogels composed of PMDV and ALG could be loaded with cell growth factors that have high activity and can control cell functions. Therefore, this system provides a cell function controllable substrate based on the controlled release of biologically active proteins.

Release proporties of ovalbumin from alginate microspheres prepared using the nozzle in spray dryer system

  • Park, Jeong-Eun;Lee, Chang-Moon;Park, Hee-Jung;Kim, Gwang-Yun;Rhee, Joon-Haeng;Lee, Ki-Young
    • 한국생물공학회:학술대회논문집
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    • 2005.04a
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    • pp.570-573
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    • 2005
  • The spray method was chiefly used to prepare alginate microspheres. Additionally due to formation at mild conditions, the alginate microspheres were coated with chitosan. The particle size of alginate microspheres increased when the sodium alginate increased. Release pattern of OVA in alginate microspheres was evaluated at PBS buffer(pH 7.4) and HCl buffer(pH 1.2). Release rate of OVA from chitosan/alginate microsphere was also lower than that with the concentration of alginate in the microspheres, the amount of OVA released from alginate microspheres increased from alginate micorsphere. Therefore, the alginate microspheres can be prepared by spray rozzle for a protein drug delivery. OVA release from the alginate microspheres was controlled by a coating with chitosan.

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Development of Poly(D,L-lactic acid) Microspheres Containing Lorazepam (로라제팜을 함유한 poly(D,L-lactic acid) 마이크로스피어 개발)

  • Choi, Han-Gon;Yoo, Bong-Kyu;Rhee, Jong-Dal;Kim, Jung-Ae;Kwon, Tae-Hyub;Woo, Jong-Soo;Yong, Chul-Soon
    • Journal of Pharmaceutical Investigation
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    • v.36 no.3
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    • pp.175-184
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    • 2006
  • Poly(D,L-lacic acid)(PLA) microshperes containing loazepam were prepared by a solvent-emulsion evaporation method and their release patterns were investigated in vitro. Various batches of microspheres with different size and drug content were obtained by changing the ratio of lorazepam to PLA, PLA concentration in the dispersed phase and stirring rate. Rod-like lorazepam crystals on microsphere surface, which were released rapidly and could act as a loading dose, were observed with increasing drug content. The release rate was increased with increase in drug contents and decrease in the molecular weight of PLA. The release rate of lorazepam for long-acting injectable delivery system in vitro, which would aid in Predicting in vivo release Profile, could be controlled by properly optimizing various factors affecting characteristics of microspheres.

Controlled Release Dosage Form of Narcotic Antagonist(II) : Biocompatibility and Pharmacokinetics of Naloxone Implant (마약길항제의 방출 제어형 제제 (제2보): 나록손 이식제제의 생체적합성 및 약물속도론적 평가)

  • Moon, Mi-Ran;Park, Joo-Ae;Lee, Seung-Jin;Kim, Hyung-Kuk;Kim, Kil-Soo
    • Journal of Pharmaceutical Investigation
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    • v.25 no.2
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    • pp.117-123
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    • 1995
  • For the effective administration of narcotic antagonist, the application of sustained release implantable systems with biodegradable polyphosphazene was examined. Using poly[(diethyl glutamate)-co-(ethyl glycinate) phosphazene], the implantable devices containing naloxone hydrochloride were prepared and in vivo implantation studies were carried out subcutaneously in rat and rabbit with this preparation for the biocompatibility and pharmacokinetics. The histological finding in rats at initial time period was the inflammation that occurred focally around the implants, but they were showed subsequent mild and limited chronic inflammations and the irreversible changes such as necrosis and degeneration of the muscle or connective tissues were not observed. Therefore the placebo and naloxone implants are considered to be biocompatible formulations histologically. In pharmacokinetic studies, the release of naloxone from the naloxone implants into blood plasma was maintained in 192 hours, but the initial burst effect was observed. If this problem was solved, the application for the narcotic antagonist sustained release systems can be expected.

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Dexamethasone Release from Glutaraldehyde Cross-Linked Chitosan Microspheres: In Vitro/In Vivo Studies and Non-Clinical Parameters Response in Rat Arthritic Model

  • Dhanaraju, Magharla Dasaratha;Elizabeth, Sheela;Poovi, Ganesan
    • Journal of Pharmaceutical Investigation
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    • v.41 no.5
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    • pp.279-288
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    • 2011
  • The Dexamethasone (DEX) loaded chitosan microspheres were prepared by thermal denaturation and chemical cross-linking method using a dierent concentration of glutaraldehyde as chemical cross-linking agent. The prepared microspheres were evaluated for the percentage of Drug Loading (DL), Encapsulation Efficiency (EE) and surface morphology by Scanning Electron Microscopy (SEM). DL and EE were found to be maximum range of 10.0 to 10.79 % and 58.19 to 64.73 % respectively. The SEM Photographs of the resultant microspheres exhibited fairly smooth surfaces and predominantly spherical in appearance. In addition, Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) shown that there was no interaction between the drug and polymer. In vitro and in vivo release studies revealed that the release of dexamethasone was sustained and extended up to 63 days and effectively controlled by the extent of cross-linking agent. Non-clinical parameters such as paw volume, hematological parameters like Erythrocyte Sedimentation Rate (ESR), Paced Cell Volume (PCV), Total Leucocytes Count (TLC), Hemoglobin (Hb), Differential Cell Count (DCC) were investigated in Fruend's Complete Adjuvant (FCA) induced arthritic rats. Radiology and histopathological studies were also performed in order to evaluate the therapeutic efficacy of the DEX-loaded microspheres in extenuating the rat arthritic model.

Enhanced Antigen Delivery Systems Using Biodegradable PLGA Microspheres for Single Step Immunization

  • Cho, Seong-Wan;Kim, Young-Kwon
    • Biomedical Science Letters
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    • v.12 no.4
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    • pp.443-450
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    • 2006
  • To demonstrate their possibilities as an enhanced vaccine delivery system, protein-loaded Poly lactide glycolide copolymer (PLGA) microspheres were prepared with different physical characteristics. Ethyl acetate (EA) solvent extraction process was employed to prepare microspheres and the effects of process parameters on drug release properties were evaluated. The biodeuadability of microspheres was also evaluated by the pH change and GPC (Gel permeation chromatography). Primary IgG antibody responses in BALB/c mice were compared with protein saline solutions as negative controls and adsorbed alum suspensions as positive controls after single subcutaneous injection for in vivo studies. The microspheres showed a erosion with a highly porous structure and did not keep their spherical shape at 45 days and this result could be confirmed by GPC. In vitro release of proteinous drug showed initial burst effect in all batches of microspheres, followed by gradual release over the next 4 weeks. PLGA microspheres were degraded until 45 days and the secondary structure of OVA was not affected by the preparation method. Enzyme-linked immunosorbent assays demonstrated that the single subcutaneous administrations of OVA-loaded PLGA microspheres induced enhanced serum IgG antibody response in comparison to negative and positive controls. These results demonstrated that microspheres providing the controlled release of antigens might be useful in advanced vaccine formulations for the parenteral carrier system.

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Polymer-Coated Liposomes for Oral Drug Delivery (I): Stability of Polysaccharide-Coated Liposomes Against Bile Salts (고분자 코팅을 이용한 경구용 리포좀의 개발(I): 다당체로 코팅된 리포좀의 담즙산염에 대한 안정성)

  • Choi, Young-Wook;Hahn, Yang-Hee
    • Journal of Pharmaceutical Investigation
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    • v.22 no.3
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    • pp.211-217
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    • 1992
  • Stabilization of liposomes against degradation by bile salts has been investigated in order to develop a liposomal model system for oral drug delivery. Two polysaccharides, amylopectin (AP) and chitin (CT), were employed to coat both empty liposomes and bromthymol blue (BTB)-encapsulated liposomes by adsorption-coating techniques. Turbidity changes and BTB-release characteristics in pH 5.6 buffer solutions with or without bile salts, sodium cholate and sodium glycocholate, were observed to compare the differences between uncoated liposomes and polysaccharide-coated liposomes. Initial turbidities of both uncoated and polysaccharide-coated liposomes in buffer solution were kept constant within 3% range during 4 hours of experiments. But they were decreased in a different manner in bile salts-containing buffer solutions, showing 10% or less decrease for polysaccharide-coated liposomes and 25% or more decrease for uncoated liposomes. BTB release from uncoated liposomes has been greatly increased upto 90% after 4 hours in bile salts-containing buffer solution, which is a clue for breakdown of liposomal vesicles. However, polysaccharide-coated liposomes showed the controlled-release pattern which is proportional to square-root of time, followed by around 50% release for the same time period. Consequently, it is possible to conclude that these polysaccharide-coated liposomes might be an available system for oral delivery of a drug which is unstable in gut environment.

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Clonazepam Release from Poly(DL-lactide-co-glycolide) Nanoparticles Prepared by Dialysis Method

  • Nah, Jae-Woon;Paek, Yun-Woong;Jeong, Young-Il;Kim, Dong-Woon;Cho, Chong-Su;Kim, Sung-Ho;Kim, Myung-Yul
    • Archives of Pharmacal Research
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    • v.21 no.4
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    • pp.418-422
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    • 1998
  • Aim of this work is to prepare poly(DL-lactide-co-glycolide) (PLGA) nanoparticles by dialysis method without surfactant and to investigate drug loading capacity and drug release. The size of PLGA nanoparticles was 269.9 $\pm$118.7 nm in intensity average and the morphology of PLGA nanoparticies was spherical shape from the observation of SEM and TEM. In the effect of drug loading contents on the particle size distribution, PLGA nanoparticles were monomodal pattern with narrow size distribution in the empty and lower drug loading nanoparticles whereas bi- or trimodal pattern was showed in the higher drug loading ones. Release of clonazepam from PLGA nanoparticles with higher drug loading contents was slower than that with lower loading contents.

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Studies on Dosage Form Design of Anticancer Drug: Release of 5-Fluorouracil from Silicone Devices Containing Water Soluble Additives (항암제(然癌劑) 제형(劑形) 개발(開發)에 관(關)한 연구(硏究) : Silicone Rubber-수용성(水溶性) 첨가제(添加劑)의 Device에서 5-Fluorouracil의 용출(溶出))

  • Kim, Sung-Ho;Choi, Jun-Shik;Back, Chae-Sun;Yu, Young-Jong;Lee, Chi-Young
    • Journal of Pharmaceutical Investigation
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    • v.16 no.1
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    • pp.1-7
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    • 1986
  • The influences of sodium chloride, polyethylene glycol 4000 and 20000 on 5-fluorouracil release from disk type silicone polymer devices were examined in isotonic phosphate buffer. These water soluble cosolvent and sodium chloride caused devices to swell in aqueous media. Sodium chloride exerted the greatest influence on drug release. The addition of water soluble cosolvent or sodium chloride to silicone polymeric devices permitted controlled release of 5-fluorouracil, presumably due to the change of the physical microstructure of silicone network, and the solubility and diffusivity of 5-fluorouracil. It seemed that the water soluble drug was released through the hydrophilic pores or pathways formed in the device by the incorporation of a water soluble cosolvent or sodium chloride.

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Preparation and Release Behavior of Atorvastatin Calcuim - Encapsulated Polyoxalate Microspheres (아토르바스타틴 칼슘을 함유한 폴리옥살레이트 미립구의 제조 및 방출거동)

  • Lee, Cheon Jung;Kim, Su Young;Lee, Hyun Gu;Yang, Jaewon;Park, Jin Young;Cha, Se Rom;Lim, Dong-Kwon;Lee, Dongwon;Khang, Gilson
    • Polymer(Korea)
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    • v.38 no.5
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    • pp.656-663
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    • 2014
  • Atorvastatin calcium-loaded polyoxalate (POX) microspheres were prepared by an emulsion solvent-evaporation/ extraction method of oil-in-oil-in-water ($O_1/O_2/W$) for sustained release. We investigated the release behavior according to initial drug ratio, molecular weight ($M_w$) and concentration of POX and concentration of emulsifier. The microsphere was characterized on the surface, the cross-section morphology and the behavior of atorvastatin calcium release for 10 days by scanning electron microscopy (SEM) and high performance liquid chromatography (HPLC). The analysis of crystallization was analyzed to use X-ray diffraction (XRD), differential scanning calorimeter (DSC) and Fourier transform infrared (FTIR). These results showed that the release behaviors can be controlled by preparation conditions.