• Title/Summary/Keyword: Protein drug delivery

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Specific Cell-Signal Targets for Cancer Chemotherapy

  • Aszalos, Adorjan
    • Archives of Pharmacal Research
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    • v.25 no.1
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    • pp.1-10
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    • 2002
  • Attempts to develop drugs, specific for cancer cells, are dealt here according to the intended cell-target. While many target specific drugs were developed, they reach only moderate successes in clinics for reasons, such as, delivery problem, lack of in vivo efficacy or toxicity. However, recent efforts focusing on the diversity of tyrosine kinases, participating in cell-signal transduction, brought fruit. The first such drug, Givec, approved by the USFDA recently, is used in clinics with great success to threat CML. The drug inhibits tyrosin kinase of bcr-abl, c-abl and v-abl. Work is progressing on other tyrosin kinase inhibitors and on other type of specific cancer cell signal protein inhibitors. These efforts are hoped to yield better cures for cancer in the near future.

Synergistic Effect of Reductase and Keratinase for Facile Synthesis of Protein-Coated Gold Nanoparticles

  • Gupta, Sonali;Singh, Surinder P.;Singh, Rajni
    • Journal of Microbiology and Biotechnology
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    • v.25 no.5
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    • pp.612-619
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    • 2015
  • We have synthesized gold nanoparticles (GNPs) using chicken feathers (poultry waste) and Bacillus subtilis RSE163. Disulfide reductase and keratinase produced by Bacillus subtilis during the degradation of chicken feather has been used to reduce Au3+ from HAuCl4 precursor to produce gold nanoparticles. The synthesized biogenic GNPs were characterized by UV-visible spectroscopy, transmission electron microscopy (TEM), and zeta potential measurements. Fourier transform infrared (FTIR) spectroscopy indicated the presence of protein capping on synthesized GNPs, imparting multifunctionality to the GNP surface. Furthermore, the nontoxic nature of biogenic GNPs was insured by interaction with Escherichia coli (ATCC11103), where TEM images and enhancement of growth rate of E. coli in log phase signified their nontoxic nature. The results indicate that the synthesis of biocompatible GNPs using poultry waste may find potential applications in drug delivery and sensing.

Rapid detection of liposome by piezoresistive cantilever sensor (고감도 압저항 외팔보 센서를 이용한 Liposome의 검침)

  • Hyun, S.J.;Kim, H.S.;Kim, Y.J.;Jung, H.I.
    • Journal of Sensor Science and Technology
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    • v.14 no.3
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    • pp.156-159
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    • 2005
  • Liposomes are microscopic spherical vesicles that form when lipids are hydrated and have been widely used for biochemical assay, drug delivery and molecular imaging. In particular, they are well known for artificial cell membranes to study cellular functions such as cell fusions and membrane proteins. Here, we firstly report the detection of liposomes by the highly sensitive microfabricated piezoresistive cantilever sensor chip and the phosphatidylserine recognition protein C2A which is chemically immobilized on the sensor surface. The signal created from the bending motion of piezoresistive cantilever after the liposome attachment has been monitored in real time.

Recent research trend for silk hydrogel (실크 하이드로겔 연구 동향)

  • Ki, Chang Seok;Kim, Hyung Hwan;Park, Young Hwan
    • Journal of Sericultural and Entomological Science
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    • v.54 no.1_2
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    • pp.6-16
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    • 2016
  • Both mechanical property and biocompatibility of silk protein has been highlighted for decades and lots of studies are trying to use it for a wide variety of applications. Recently, silk-based hydrogel has received great attention in biomedical field such as drug delivery and tissue engineering since silk protein presents a unique hydrogel forming mechanism as well as cyto-compatibility. Silk hydrogels are formed via tremendous physical and chemical techniques and their biomedical applications are extensively explored. In this review, various types and fabrication methods of silk hydrogels are presented and also the recent research trend of silk hydrogel-based applications is summarized.

Antigenicity of Protein Entrapped in Poly(lactide-co-glycolide) Microspheres (폴리락티드-글리콜리드 마이크로스피어에 봉입된 단백질의 항원성 평가)

  • Song, Seh-Hyon;Cho, Seong-Wan;Shin, Taek-Hwan;Yoon, Mi-Kyoung;Choi, Young-Wook
    • Journal of Pharmaceutical Investigation
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    • v.31 no.3
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    • pp.191-196
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    • 2001
  • Biodegradable polymeric microspheres were studied for their usefulness as carriers for the delivery of vaccine antigens. However, protein antigen could be denatured during microencapsulation processes due to the exposure to the organic phase and stress condition of cavitation and shear force. Therefore this study was carried out to re-evaluate the degree of protein denaturation during microencapsulation with poly(lactide-co-glycolide) (PLGA) copolymer. PLGA microspheres containing ovalbumin (OVA), prepared by W/O/W multiple emulsification method, were suspended in pH 7.4 PBS and incubated with shaking at $37.5^{\circ}C$. Drug released medium was collected periodically and analyzed for protein contents by micro-BCA protein assay. In order to evaluate the protein integrity, release medium was subjected to the analyses of SDS-PAGE and size exclusion chromatography (SEC). And enzyme-linked immunosorbent assay (ELISA) was introduced to measure the immunoreactivity of entrapped OVA and to get an insight into the three-dimensional structure of epitope. The structures of entrapped protein were not affected significantly by the results of SDS-PAGE and SEC. However, immunoreactivity of released antigen was varied, revealing the possibility of protein denaturation in some microspheres when it was evaluate by ELISA method. Therefore, in order to express the degree of protein denaturation, antigenicity ratio (AR) was obtained as follows: amount of immunoreactivity of OVA/total amount of OVA released ${\times}100(%)$. ELISA method was an efficient tool to detect a protein denaturation during microencapsulation and the comparison of AR values resulted in more accurate evaluation for immunoreactivity of entrapped protein.

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Stability in Plasma and Intracellular Uptake of Thermally Denatured Protein-coated anionic Liposomes (열변성 단백질이 결합된 음이온성 리포솜의 혈장 내 안정성 및 세포 내 이입 평가)

  • Lee, Mi-Jung;Hwang, In-Young;Kim, Sung-Kyu;Jung, Suk-Hyun;Jeong, Seo-Young;Seong, Ha-soo;Cho, Sun-Hang;Shin, Byung-Cheol
    • Journal of Pharmaceutical Investigation
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    • v.39 no.6
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    • pp.423-429
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    • 2009
  • Liposomes have been used as one of the efficient carriers for drug delivery. In this study, anionic liposomes of which surface was modified by using both electrostaic interaction between anionic liposomes and cationically charged BSA molecules at lower pH than isoelectric point (pI) of BSA and denaturation of the BSA-coated liposomes by thermal treatment. The thermally denatured BSA-coated liposomes (DBAL) had mean particle diameter of 125.2${\pm}$1.7 nm and zeta potential value of -22.4${\pm}$4.5 mV. Loading efficiency of model drug, doxorubicin (DOX), into liposomes was 83.0${\pm}$2.6%. Results of in vitro stability study of DBAL in blood plasma showed that the mean particle diameter of DBAL 400 did not increase in blood plasma and adsorption of plasma protein was much less than plain or anionic liposomes. Intracellular uptake of DBAL 400 evaluated by confocal microscopy observation was higher than that of PEG liposomes.

Pyridoxine Deficiency on Neurotransmitters in the Developing Rat Brain - Catecholamine Metabolism- (Pyridoxine결핍이 뇌의 신경전달물질에 미치는 영향 - Catecholamine 대사 -)

  • Choi, Hay-Mie;Kang, Soon-Ah
    • Journal of Nutrition and Health
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    • v.17 no.3
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    • pp.199-209
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    • 1984
  • Pregnant rats were fed a pyridoxine deficient diet during the gestation and lactation. DEF I group received the deficient diet from delivery ; DEF II group, from the 15 th day of gestation. Body and brain weights, brain protein, DNA, RNA, plasma GOT and GPT, and catecholamines were measured. Effect of MAO inhibiting drug, pargyline, was determined. Brain protein, DNA, and RNA of offsprings of deficient groups were significantly lower than the control group, but RNA/ DNA, brain weight/DNA, and protein/DNA show that cell number were more affected than cell size by the pyridoxine deficiency during the 3rd week of gestation and lactation. Plasma GOT activities were more significantly different than plasma GPT between the control and deficient group. Brain norepinephrine of offsprings of deficient group were significantly lower than the control, but brain dopamine content was not significantly different from the control. At 2nd and 3rd week, norepinephrine was significantly depressed in deficient groups. Pargyline treatment affected a 1.2 fold increase in catecholamines in 3hr while the control had a 1.5 fold increase. Thus norepinephrine and dopamine synthesis was depressed in the deficient groups. Dopaminergic neurons may be less dependent on pyridoxine level than neurons from norepinephrine. Pyridoxine deficiency in maternal diet is not so critical to brain catecholamines of offspring except to the neonatal rats.

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Comparison of Analysis Methods for Detection of Replication Competent Virus and Functional Titers of HIV-l Based Lentivirus Vector (HIV-l 유래 렌티바이러스 벡터의 복제가능 바이러스 검출과 역가측정 분석방법 비교)

  • Chang Seok Kee;Oh Il Ung;Jeong Jayoung;Ahn Kwang Soo;Sohn Yeowon
    • YAKHAK HOEJI
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    • v.49 no.3
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    • pp.217-224
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    • 2005
  • Human Immunodeficiency Virus type 1 (HIV-l) based lentivirus vector has demonstrated great potential as gene therapy vectors mediating efficient gene delivery and long-term transgene expression in both dividing and nondividing cells. However, for clinical studies it must be confirmed that vector preparations are safe and not contaminated by replication competent lentivirus (RCL) related to the parental pathogenic virus, HIV-l. In this study, we would like to establish the method for titration and RCL detection of lentivirus vector. The titration was determined by vector expression containing the green fluorescent protein, GFP in transduced cells. The titer was $1{\times}10^7$ Transducing Unit/ml in the GFP expression assay and $8.9{\times}10^7$ molecules/ml in the real-time PCR. Also, for the detection of RCL, we have used a combination method of PCR and p24 antigen detection. First, PBS/psi and VSV-G region in the genomic DNA of transduced cells was detected by PCR assay. Second, transfer and expression of the HIV-1 gag gene was detected by p24 ELISA. In an attempt to amplify any RCL, the transduced cells were cultured for 3 weeks (amplification phase) and the supernatant of amplified transduced cell was used for the second transduction to determine whether a true RCL was present (indicator phase). Analysis of cells and supernatant at day 6 in indicator phase were negative for PBS/psi, VSV-G, and p24 antigen. These results suggest that they are not mobilized and therefore there are no RCL in amplification phase. Thus, real-time PCR is a reliable and sensitive method for titration and RCL detection of lentivirus vector.

Studies on the Effective Drug Delivery System Using Naked Plasmid DNA for the Erythropoietin Expression in vivo

  • Park, Yeong-Seop;Jeong, Dong-Geon;An, Jin-Ho;Choe, Cha-Yong;Ju, Hyeon
    • 한국생물공학회:학술대회논문집
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    • 2003.04a
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    • pp.582-586
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    • 2003
  • There has been interest in developing gene therapy based on naked plasmid DNA for treating serum protein deficiencies and human erythropoietin (hEPO) is one of the candidate for gene therapy being Investigated most enthusiastically. We constructed novel plasmid DNA vectors pVAC-hEPOI/II/III which contain one, two, three hEPO gene(s) respectively for producing high level expression and secretion of hEPO in vitro and in vivo. NIH3T3 and COS7 cells were transfected transiently with these vectors and increase in hEPO expression in medium reached 2-5 fold in comparison with pSecTagB-hEPO. Intra muscular administrations of pVAC-hEPOI/II/III vectors into mice resulted in high level secretion of hEPO in the serum and corresponding increases in hematocrit level. In conclusion the transduction efficiency of naked plasmid vectors is one of the critical factors of a gene delivery system and these novel plasmid vectors will contribute to various gene therapy based on naked plasmid DNA.

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Bioinspired Polymers that Control Intracellular Drug Delivery

  • Allan S. Hoffman;Patrick S. Stayton;Oliver-Press;Niren-Murthy;Chantal A. Lackey;Charles-Cheung;Fiona-Black;Jean Campbell;Nelson Fausto;Themis R. Kyriakides;Paul-Bornstein
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.6 no.4
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    • pp.205-212
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    • 2001
  • One of the important characteristics of biological systems os their ability to change im-portant properties in response to small environmental signals. The molecular mechanisms that biological molecules utilize to sense and respond provide interesting models for the development of "smart" polymeric biomaterials with biomimetic properties. An important example of this is the protein coat of viruses, which contains peptide units that facilitate the trafficking of the virus into the cell via endocytosis, then out of the endosome into the cytoplasm, and from there into the nucleus, We have designed a family of synthetic polymers whose compositions have been de-signed to mimic specific peptides on viral coats that facilitate endosomal escape. Our biomimetic polymers are responsive to the lowered pH whinin endosomes, leading to distruption of the en-dosomal membrane and release of important biomolecular druges such as DNA, RNA, peptides and proteins to the cytoplasm before they are trafficked to lysosomes and degraded by lysosomal en-zymes. In this article, we review our work on the design, synthesis and action of such smart, pH-sensitive polymers.

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