• Title/Summary/Keyword: Protein drug delivery

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Biological Effects Of Flurbiprofen Loaded Chitosan To Gingival Fibroblast (Flurbiprofen 함유 키토산 제제가 치은 섬유아세포에 미치는 영향)

  • Chung, Chong-Pyoung;Park, Yoon-Jeong;Lee, Seung-Jin;Rhyu, In-Cheol;Choi, Sang-Mook
    • Journal of Periodontal and Implant Science
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    • v.26 no.1
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    • pp.317-333
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    • 1996
  • The main goal of periodontal regeneration is to be achieved by epithelial exclusion, periodontal ligament cell activation or alveolar bone regeneration. The purpose of this study was to investigate on the physico- chemical and biological characteristics of biodegradable chitosan beads. Chitosan beads were fabricated by ionic gelation with sodium tripolyphosphate and they had the size in 300um diameter. As therapeutic agent, flurbiprofen was incorporated into the beads by 10, 20% loading contents. The release of drugs from the chitosan beads was measured in vitro. Also, biological activity tests of flurbiprofen loaded chitosan beads including cytotoxicity test, ihhibition of $IL-1{\beta}$ production, suppression to $PGE_2$ production, collagenase inhibition test, the ability of total protein synthesis, and tissue response were evaluated. The amount of flurbiprofen released from chitosan was 33-50% during 7 days. Minimal cytotoxicity was observed in chitosan beads. Flurbiprofen released from chitosan beads significantly suppressed the $IL-1{\beta}$ production of monocyte, $PGE_2$ production and markedly inhibited collagenase activity. Meanwhile, flurbiprofen released from this system showed increased ability for protein synthesis. Throughout 4 -week implantation period, no significant inflammatory cell infiltrated around chitosan bead and also fibroblast like cell types at the beads - tissue interface were revealed with gradual degradation of implanted chitosan beads. From these results, it was suggested that flurbiprofen loaded chitosan beads can be effectively useful for biocompatible local delivery system in periodontal regeneration.

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Effect of Vehicles and Enhancers on the in vitro Skin Penetration of Aspalatone and Its Enzymatic Degradation Across Rat Skins

  • Gwak, Hye-Sun;Chun, In-Koo
    • Archives of Pharmacal Research
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    • v.24 no.6
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    • pp.572-577
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    • 2001
  • The feasibility of skin penetration was studied for aspalatone (AM, acetylsalicylic acid maltol ester), a novel antithrombotic agent. In this studys hairless mouse dorsal skins were used as a model to select composition of vehicle and AM. Based on measurements of solubility and partition coefficient, the concentration of PC that showed the highest flux for AM across the hairless mouse skin was found to be 40%. The cumulative amount permeated at 48 h, however, appear inadequate, even when the PC concentration was employed. To identify a suitable absorption enhancer and its optimal concentration for AM, a number of absorption enhancers and a variety of concentration were screened for the increase in transdermal flux of AM. Amongst these, linoleic acid (LOA) at the concentration of 5% was found to have the largest enhancement factor (i.e., 132). However, a further increase in AM flux was not found in the fatty acid concentration greater than 5%, indicating the enhancement effect is in a bell-shaped currie. In a study of the effect of AM concentration on the permeation, there was no difference in the permeation rate between 0.5 and 1% for AM, below its saturated concentration. At the donor concentration of 2%, over the saturated condition, the flux of AM was markedly increased. A considerable degradation of AM was found during permeation studies, and the extent was correlated with protein concentrations in the epidermal and serosal extracts, and skin homogenates. In rat dorsal skins, the protein concentration decreased in the rank order of skin homogenate > serosal extract > epidermal extract. Estimated first order degradation rate constants were $6.15{\pm}0.14,{\;}0.57{\pm}0.02{\;}and{\;}0.011{\pm}{\;}0.004{\;}h^{-1}$ for skin homogenate, serosal extract and epidermal extract, respectively. Therefore, it appeared that AM was hydrolyzed to some extent into salicylmaltol by esterases in the dermal and subcutaneous tissues of skin. taken together, our data indicated that transdermal delivery of AM is feasible when the combination of PC and LOA is used as a vehicle. However, since AM is not metabolically stable, acceptable degradation inhibitors may be nervessary to fully realize the transdermal delivery of the drug.

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Preparation and Properties of PEG Modified PNVP Hydrogel

  • Son, Young-Kyo;Kim, Ji-Heung;Jeon, Young-Sil;Chung, Dong-June
    • Macromolecular Research
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    • v.15 no.6
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    • pp.527-532
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    • 2007
  • Polymer hydrogel has attracted considerable interest as a soft material which is finding expanding applications in pharmaceutics and various biomedical fields. In this work, modified PNVP hydrogels were synthesized by crosslinking polymerization of NVP monomer in the presence of PEG macromer with a methoxy end. The effect of the tethered PEG chain on the properties of the hydrogel was investigated in terms of its swelling capacity, compression gel strength, and the morphology of the resulting hydrogels. These PEG-modified PNVP hydrogels possessed good biocompatibility and a decreased protein (fibrinogen) adsorption, thereby indicating their potential as novel drug delivery matrices and scaffold for tissue engineering.

Current Status of the Research and Development of Bispecific Antibodies

  • Kwon, Sun-Il
    • Biomedical Science Letters
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    • v.26 no.3
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    • pp.136-148
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    • 2020
  • A bispecific antibody (BsAb) is an artificial protein containing two kinds of specific antigen binding sites. BsAb can connect target cells to functional cells or molecules, and thus stimulate a directed immune response. Last several decades a wide variety of bsAb formats and production technologies have been developed. BsAbs are constructed either chemically or biologically, exploiting techniques like cell fusion and recombinant DNA technologies. There are over 100 different formats of bsAb so far developed, but they could be classified into the two main categories such as Fc-based (with a Fc region) bsAbs and fragment-based (without a Fc region) bsAbs. BsAb has a broad application prospect in tumor immunotherapy and drug delivery. Here, we present a brief introduction to the structure of antibody, pharmacological mechanisms of antibodies and the trend in the production technologies of therapeutic antibodies. In addition, we address a review on the current status of various bsAb format development and their production technologies together with global situation in the clinical studies of bsAb.

Controllable Movement of the Azobenzene Linked Crown Ether Conjugated Liposome

  • Seo, Eun-Seok;Kim, Soo-Hyun;Kim, Jin-Seok;Kim, Byung-Kyu
    • 제어로봇시스템학회:학술대회논문집
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    • 2005.06a
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    • pp.1158-1162
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    • 2005
  • Drug delivery systems have been developed to reduce the side toxicity of drugs by localizing them in the site of action. But it depends on the circulation of the blood and it doesn't have the function of locomotive mechanism of itself for searching for the region of disease. However, this problem could be solved by nanobot which have the locomotive function. So, we mimic the movement of cell that can move in a human body. In this paper, to polymerize the encapsulated actin within the liposome, electroporation technique is employed. In order to optimize polymerization and depolymerization of the liposome, we compare the time of polymerization and depolymerization by concentration of crown ether. we synthesis the liposome which contain azobenzene Linked crown Ether conjugated Actin protein. Azobenze linked crown ether holds the K+ ion by exposure of UV light and this disturbs the actin polymerization. In result, UV light could control the liposome growth. Finally, we could develop the liposome robot and control the growth and degeneration of the liposome by external stimuli such s UV light. The merit of the controlling by UV light doesn't need to inject proteins which induce polymerization and depolymerization of actin protein.

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Particle Size Control of Poly(Lactide-co-Glycolide) Microspheres for Oral Antigen Delivery Systems (경구용 항원 수송체 모델로서 폴리락티드-글리콜리드 마이크로스피어의 입자도 조절)

  • Song, Il-Yong;Song, Seo-Hyun;Song, Woo-Heon;Cho, Seong-Wan;Choi, Young-Wook
    • Journal of Pharmaceutical Investigation
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    • v.29 no.4
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    • pp.315-321
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    • 1999
  • Poly (lactide-co-glycolide) (PLGA) microspheres containing ovalbumin (OVA) as a model protein drug were prepared by double emulsification method, and various conditions such as mixing rate, volume of outer phase and isopropyl alcohol concentration in outer phase during secondary emulsification were observed to control the size of microspheres. In addition, entrapment efficiency of OVA and protein denaturation were also evaluated. As the rate of stirring was increased, the size of particles was decreased. But excessive stirring increased the particle size of microspheres. In a preparation condition of small volume of outer phase, the particle size was decreased but the entrapment efficiency was increased. Adding isopropyl alcohol to outer phase decreased the size of particles, but increased the entrapment efficiency. Microparticles should have smaller size than $10\;{\mu}m$ to be uptaked by Peyer's patch in small intestine. High speed of mixing and relatively small volume of outer phase are needed to reduce the size. In addition, appropriate amount of isopropyl alcohol in outer phase also plays an important role in size reduction of PLGA microspheres.

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Coaxial Nozzle Electrospraying of Polymer Solutions: Use of Dispersant Flow (고분자 용액의 동축 이중노즐 전기분무: 분산제 흐름의 사용)

  • Kim, Min-Young;Lee, Jong-Hwi
    • Polymer(Korea)
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    • v.35 no.3
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    • pp.254-259
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    • 2011
  • In electrospraying of polymer solutions, metal sample collectors are often ineffective in fully removing solvent from sprayed particles and recovering redispersable sprayed particles. Herein, a novel electro spraying system, where sprayed particles were dispersed into laminar flow of dispersant (coagulation liquid), was designed for the nano-encapsulation of protein drugs. Chitosan and polyacrylic acid were used as the encapsulation materials. Aggregation of particles could be prevented by using this new electrospraying system, and unimodal size distribution was observed at an applied voltage between 4~16 kV and a low flow rate. The effects of the applied voltage on mean particle size were not significant on the other hand.

Islet function within a multilayer microcapsule and efficacy of angiogenic protein delivery in an omentum pouch graft

  • McQuilling, J.P.;Pareta, R.;Sivanandane, S.;Khanna, O.;Jiang, B.;Brey, E.M.;Orlando, G.;Farney, A.C.;Opara, E.C.
    • Biomaterials and Biomechanics in Bioengineering
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    • v.1 no.1
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    • pp.27-39
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    • 2014
  • We have previously described a new multilayer alginate microcapsule system, and the goals of the present study were to assess the in vitro function of islets encapsulated in its inner layer, and the angiogenic ability of FGF-1 delivered from the external layer in an omentum pouch. Following isolation and culture, islets were encapsulated in the inner core of microspheres ($500-600{\mu}m$ in diameter) with a semi-permeable poly-L-ornithine (PLO) membrane separating two alginate layers, and both unencapsulated and encapsulated islet function was assessed by a dynamic glucose perifusion. For angiogenesis experiments, one group of microcapsules without FGF-1 (control) and another (test) containing FGF-1 with heparin encapsulated in the external layer were made. One hundred microcapsules of each group were transplanted in Lewis rats (n = 5/group) and were retrieved after 14 days for assessment of angiogenesis. Glucose perifusion of unencapsulated and encapsulated islets resulted in similar stimulation indices. The release of FGF-1 resulted in increased vascular density compared to controls. In conclusion, islets encapsulated in the core of multilayer alginate microcapsules maintain functionality and the microcapsule's external layer is effective in delivery of FGF-1 to enhance graft neovascularization in a retrievable omentum pouch.

In Vitro Stability of Liposomes Containing Newly Synthesized Glycolipid (신규 합성 당지질 함유 리포솜의 In Vitro 안정성)

  • Song, Chung-Kil;Jung, Soon-Hwa;Seong, Ha-Soo;Cho, Sun-Hang;Shin, Byung-Cheol
    • Journal of the Korean Chemical Society
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    • v.51 no.1
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    • pp.43-50
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    • 2007
  • Liposomes having particle size from several tens to hundreds nanometers are efficient carriers for injectable drug delivery. Enhancement of liposome stability in bloodstream has been studied because of its relatively short circulation time and fast clearance from human body by reticuloendothelial system (RES) in blood vessel. In this study, new disaccharide-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) derivatives in which lactose or sucrose as the disaccharide molecule was conjugated covalently to DSPE were synthesized. Liposomes of which surface had disaccharide molecules were prepared by incorporating the disaccharide-DSPE into liposomes as one of their lipid components. Particle size of the prepared liposomes was approximately 100 nm. The liposomes of which surface were modified with the disaccharide-DSPE showed -25 mV of zeta potential value due to the presence of hydroxyl groups on their surface, while the unmodified control liposomes showed -10 mV of zeta potential value. Loading efficiency of model drug, doxorubicin, into liposomes was about 90%. Stability of the disaccharide-modified liposomes in vitro was evaluated by monitoring the amount of protein adsorption and particle size of the liposomes in serum. Disaccharide-modified liposomes were more stable in serum than unmodified control liposomes or polyethyleneglycol (PEG)-modified liposomes due to less adsorption of serum protein and hence less increase of their particle size. The liposomes of which surface was modified with disaccharide-DSPE conjugate can be used as long-circulating carriers for drugs having high toxicity or short half-life time due to their enhanced stability in blood circulatory system.

Recent Progress in Mussel-inspired Catechol-conjugated Chitosan Hemostats (홍합 모사 카테콜기가 도입된 키토산 지혈제 연구 동향)

  • Seongyeon Jo;Soomi Kim;Chanwoo Park;Seungwon Hong;Hong Kee Kim;Ji Hyun Ryu
    • Journal of Adhesion and Interface
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    • v.24 no.4
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    • pp.113-119
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    • 2023
  • Since it was reported that the unusual amino acid DOPA in synergy with lysine and histidine residues found in mussel adhesive proteins plays a pivotal role in mussel adhesion in underwater environments, there has been a burgeoning development of various catecholamines-based adhesives for biomedical applications. Among these, catechol-conjugated chitosan, containing catecholamine, featuring multiple catechol groups within its aminerich chitosan backbone, has found versatile utility in fields, such as tissue adhesion, wound dressing, tissue healing, hemostats, drug delivery systems, and tissue engineering scaffolds. Significantly, chitosan-catechol is a mussel-inspired material approved by both US Food and Drug Administration (FDA) and KR Ministry of Food and Drug Safety (MFDS) for its effectiveness in hemostasis. This review focuses on 1) general aspects of catechol-conjugated chitosan, highlighting catechol group integration into chitosan backbones, 2) examination of proposed mechanisms of hemostasis, and 3) exploration of diverse physical forms, including solution, hydrogels, patches, and thin films with practical applications inapplicable to hemostasis.