Abstract：
PURPOSE:The aim of the study is to determine whether a biodegradable elastomeric device that uses an osmotic pressure delivery mechanism can release different therapeutic proteins at a nearly constant rate in nanomolar concentrations with high bioactivity, given the same formulation conditions. Vascular endothelial growth factor (VEGF) and interleukin-2 (IL-2) were embedded in the device as sample therapeutic proteins, and their release and bioactivity were compared to that achieved previously with interferon-gamma (IFN-gamma). METHODS:A photo-cross-linkable biodegradable macromer consisting of acrylated star(epsilon-caprolactone-co-D,L-lactide) was prepared. VEGF, IL-2, and IFN-gamma were co-lyophilized with serum albumin and trehalose at different ratios and were then embedded into the elastomer by photo-cross-linking the lyophilized particles in a macromer solution. The protein mass and the bioactivity in the release supernatant were measured by enzyme-linked immunosorbent and cell-based assays. RESULTS:VEGF, IL-2, and IFN-gamma were released at the same, nearly constant rate of 25.4 ng/day for over 18 days. Using the optimum elastomer formulation, the release profiles of the proteins were essentially identical, and their rates were linear and constant. Cell-based bioactivity assays showed that 70 and 88% of the released VEGF and IL-2, respectively, were bioactive. The rate of protein release can be adjusted by changing the trehalose loading concentration in the elastomer matrix without altering the linear nature of the protein release kinetics. The elastomeric device degraded in PBS buffer within 85 days. CONCLUSIONS:The elastomer formulation shows promising potential as a sustained protein drug delivery vehicle for local delivery applications.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Gu F,Neufeld R,Amsden Bdoi
10.1007/s11095-006-9750-6subject
Has Abstractpub_date
2006-04-01 00:00:00pages
782-9issue
4eissn
0724-8741issn
1573-904Xjournal_volume
23pub_type
杂志文章abstract：:Moisture sorption characteristics and the effect of moisture content on the compression properties of two dextrose-based directly compressible diluents, namely, Emdex (diluent A) and Sweetrex (diluent B) were studied. Both diluents sorbed moisture rapidly at relative humidities greater than 60%. For both the diluents,...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015889414533
更新日期：1991-03-01 00:00:00
abstract：:Seven healthy, male volunteers were entered into a randomized, open crossover study of the gastrointestinal transit of two enteric-coated 500-mg naproxen tablets. Two radiolabeled tablets were given to each volunteer on two occasions separated by 7 days, once in the fasted state and once after breakfast. Radiolabeling...
journal_title：Pharmaceutical research
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1023/a:1015858829187
更新日期：1992-11-01 00:00:00
abstract：PURPOSE:In this study, modulation of the immune response against diphtheria toxoid (DT) by various adjuvants in transcutaneous immunization (TCI) with microneedle array pretreatment was investigated. METHODS:TCI was performed on BALB/c mice with or without microneedle array pretreatment using DT as a model antigen co-...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-9874-6
更新日期：2009-07-01 00:00:00
abstract：:A simple viscometric method was used to quantify mucin-polymer bioadhesive bond strength. Viscosities of 15% (w/v) porcine gastric mucin dispersions in 0.1 N HCl (pH 1) or 0.1 N acetate buffer (pH 5.5) were measured with a Brookfield viscometer in the absence (eta m) or presence (eta t) of selected neutral, anionic, a...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015812615635
更新日期：1990-05-01 00:00:00
abstract：PURPOSE:This study addresses the effect of freezing and thawing on a therapeutic monoclonal antibody (mAb) solution and the corresponding buffer formulation. Particle formation, crystallization behaviour, morphology changes and cryo-concentration effects were studied after varying the freezing and thawing rates, buffer...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2378-5
更新日期：2018-03-19 00:00:00
abstract：:(+)-Propranolol was infused at two rates into the pyloric vein (a portal vein tributary) of 15 male Sprague Dawley rats until apparent steady-state conditions were established (i.e., 8 hr at each rate). One group (n = 7) received the high dose (40 micrograms/min/kg) first, and in the other group (n = 8) the low dose (...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018921306200
更新日期：1994-03-01 00:00:00
abstract：PURPOSE:Cannabinoids have been associated with tumor regression and apoptosis of cancer cells. Recently, we have shown that R(+)-methanandamide (R(+)-MA) induces apoptosis of H4 human neuroglioma cells via a mechanism involving de novo expression of the cyclooxygenase-2 (COX-2) enzyme. The present study investigated a ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-8815-2
更新日期：2006-01-01 00:00:00
abstract：:Monte Carlo simulation technique used to evaluate the effect of the arrangement of concentrations on the efficiency of estimation of population pharmacokinetic parameters in the preclinical setting is described. Although the simulations were restricted to the one compartment model with intravenous bolus input, they pr...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016267811074
更新日期：1995-05-01 00:00:00
abstract：PURPOSE:The discovery of nano drug delivery system has rendered a great hope for improving cancer therapy. However, there are some inevitable obstacles that constrain its development, such as the physical and biological barriers, the toxicity of carrier materials and the physiological toxicity of drugs. Here, we report...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-019-2709-1
更新日期：2019-12-10 00:00:00
abstract：PURPOSE:Heparin immobilized porous poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres were prepared for sustained release of basic fibroblast growth factor (bFGF) to induce angiogenesis. MATERIALS AND METHODS:Porous PLGA microspheres having primary amine groups on the surface were prepared using an oil-in-water (O/...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9039-9
更新日期：2006-08-01 00:00:00
abstract：PURPOSE:Nine common excipients were examined to determine their ability to cause disproportionation of the HCl salt of a a weakly basic compound. The goal was to determine which excipients were problematic and correlate the results to known properties such as surface pH, slurry pH, or molecular structure. Such a correl...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1002-y
更新日期：2013-06-01 00:00:00
abstract：PURPOSE:The purpose of this study was to obtain an in vitro/in vivo correlation for the sustained release of a protein from poly(ethylene glycol) terephthalate (PEGT)/poly(butylene terephthalate) (PBT) microspheres. METHODS:Radiolabeled lysozyme was encapsulated in PEGT/PBT microspheres via a water-in-oil-in-water emu...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/B:PHAM.0000019303.12086.d1
更新日期：2004-03-01 00:00:00
abstract：PURPOSE:Some therapeutic peptides exhibit amyloidogenic properties that cause insolubility and cytotoxicity against neuronal cells in vitro. Here, we characterize the conformational change in monomeric therapeutic peptide to its fibrillar aggregate in order to prevent amyloidogenic formation during clinical application...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000033016.36825.2c
更新日期：2004-07-01 00:00:00
abstract：:The pharmacokinetics of Sb was examined in 29 patients with cutaneous leishmaniasis following the intramuscular administration of a dose of sodium stibogluconate equivalent to 600 mg of Sb. Blood was sampled at different time intervals from each patient and Sb was measured in whole blood by electrothermal atomic absor...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016251023427
更新日期：1995-01-01 00:00:00
abstract：PURPOSE:Models to predict membrane-water partition coefficients (Kp) as a function of drug structure, membrane composition, and solution properties would be useful. This study explores the partitioning of dexamethasone (Dex) and its ionizable 21-phosphate (Dex-P) in liposomes varying in acyl chain length, physical stat...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1143-z
更新日期：2013-12-01 00:00:00
abstract：BACKGROUND:Little is known about the affinity and stability of 99mTc-labeled 2-methoxyisobutylisonitrile (99mTc-MIBI) and tetrofosmin (99mTc-TF) for imaging of multiple drug resistance transporters in cancer. We examined the affinity of 99mTc-labeled compounds for these transporters and their stability. METHODS:99mTc-...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2548-5
更新日期：2018-11-29 00:00:00
abstract：PURPOSE:This study aims to develop a characterization method for coating structure based on image analysis, which is particularly promising for the rational design of coated particles in the pharmaceutical industry. METHODS:The method applies the MATLAB image processing toolbox to images of coated particles taken with...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9805-y
更新日期：2009-04-01 00:00:00
abstract：PURPOSE:Tumor vascular normalization by antiangiogenic agents may increase tumor perfusion but reestablish vascular barrier properties in CNS tumors. Vascular priming via nanoparticulate carriers represents a mechanistically distinct alternative. This study investigated mechanisms by which sterically-stabilized liposom...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0823-4
更新日期：2012-12-01 00:00:00
abstract：PURPOSE:The relationship between rat intestinal permeability (Papp) of a range of hydrophilic probe molecules and probe geometry was examined. METHODS:Molecules studies included mannitol, the polyethylene glycols (PEGs) 400, 900, and 4000, the dextran conjugated dye Texas Red (MW 3000) and the polysaccharide inulin (M...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016091915733
更新日期：1996-10-01 00:00:00
abstract：PURPOSE:The type and relative importance of saturated and unsaturated phospholipid components of surfactant within the epithelial lining fluid (ELF) of the inner and outer surfaces of the lung is not known. METHODS:Seven healthy dogs were anesthetized and a bronchoalveolar lavage (BAL) was performed, immediately follo...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-7677-y
更新日期：2005-11-01 00:00:00
abstract：:Nanoparticles, including lipopolyamines leading to lipoplexes, liposomes, and polyplexes are targeted drug carrier systems in the current search for a successful delivery system for polynucleic acids. This review is focused on the impact of gene and siRNA delivery for studies of efficacy, pharmacodynamics, and pharmac...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-008-9646-8
更新日期：2009-01-01 00:00:00
abstract：PURPOSE:The aim was to investigate the influence of polymer content and molecular weight on the morphology and heat- and moisture-induced transformations, as indicators of stability, of spray-dried composite particles of amorphous lactose and poly(vinylpyrrolidone) (PVP). METHODS:Amorphous lactose and composite partic...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1024462306941
更新日期：2003-07-01 00:00:00
abstract：:High molecular weight drugs in general, and peptides in particular, are usually delivered by parenteral route because they are poorly absorbed or degraded in the gastrointestinal tract. To optimize therapy, it is desirable to search for nonparenteral routes of administration and to deliver the drug in a controlled-rel...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018948924992
更新日期：1993-06-01 00:00:00
abstract：PURPOSE:The purpose of this study was to evaluate glucose responsiveness in HepG2 human hepatoma cells transduced by a recombinant adeno-associated virus (rAAV) vector containing the insulin gene promoter. and to investigate the effect of protamine sulfate on rAAV-mediated gene delivery. METHODS:Recombinant AAV vector...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1010923924844
更新日期：2001-07-01 00:00:00
abstract：PURPOSE:To study the structure and function of the intestinal H+/ peptide transporter PET1, we compared its amino acid sequence with those of related transporters belonging to the oligopeptide transporter family PTR, and with more distant transporter families. METHODS:We have developed a new approach to the sequence a...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012070726480
更新日期：1997-04-01 00:00:00
abstract：PURPOSE:Since a previous qualitative study carried out by us showed the existence of an important influence of the particle size on the percolation thresholds and taking into account that the existing theoretical models can only provide qualitative explanation to this influence, the purpose of this work is to carry out...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016088424993
更新日期：1996-03-01 00:00:00
abstract：PURPOSE:In this work a novel pH-responsive nanoscale polymer network was investigated for potential applications in nanomedicine. These consisted of a polybasic core surface stabilized with poly(ethylene glycol) grafts. The ability to control swelling properties via changes in core hydrophobicity and crosslinking feed ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9704-2
更新日期：2009-01-01 00:00:00
abstract：PURPOSE:The objective of the work was to evaluate the potential of hyaluronan-based nanoparticles as tumor-targeting nano-systems for CD44-overexpressed cancer therapy. METHODS:The synthesized amphiphilic cholesteryl succinoyl hyaluronan (Chol-Suc-HA) conjugates self-assembled into docetaxel(DTX)-loaded nanoparticles ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1393-4
更新日期：2014-11-01 00:00:00
abstract：:Liver fibrosis is a pathological condition originating from liver damage that leads to excess accumulation of extracellular matrix (ECM) proteins in the liver. Viral infection, chronic injury, local inflammatory responses and oxidative stress are the major factors contributing to the onset and progression of liver fib...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-014-1497-x
更新日期：2015-02-01 00:00:00
abstract：PURPOSE:Study the radiolysis of solid-state metoclopramide hydrochloride at various absorbed doses. Elucidate the structure of the degradation products to gain information on the radiolysis mechanisms. METHODS:Solid-state metoclopramide samples were irradiated at several doses with gamma rays and high-energy electrons...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-0019-x
更新日期：2006-06-01 00:00:00
