Abstract:
:A method to provide near-constant sustained release of high molecular weight, water-soluble proteins from polyanhydride microspheres is described. The polyanhydrides used were poly(fatty acid dimer) (PFAD), poly(sebacic acid) (PSA), and their copolymers [P(FAD-SA)]. P(FAD-SA) microspheres containing proteins of different molecular sizes--lysozyme, trypsin, heparinase, ovalbumin, albumin, and immunoglobulin--were prepared by a solvent evaporation method using a double emulsion. The microspheres containing proteins were spherical, with diameters of 50-125 microns, and encapsulated more than 80% of the protein, irrespective of the protein used. Enzymatic activity studies showed that encapsulation of enzymes inside polyanhydride microspheres can protect them from activity loss. When not placed inside polyanhydride microspheres, trypsin lost 80% of its activity in solution at 37 degrees C at pH 7.4 in 12 hr, whereas inside the polyanhydride microspheres the activity loss was less than 10% under these conditions. About 47% of the enzymatic activity of heparinase encapsulated in the microspheres was lost at 37 degrees C in 24 hr, while in solution it lost over 90% of its activity. The protein-loaded microspheres displayed near-zero-order erosion kinetics over 5 days as judged by the release of sebacic acid (SA) from the microspheres. The microspheres degraded to form SA and FAD monomers. All proteins were released at a near-constant rate without any large initial burst, irrespective of polymer molecular weight and protein loading. The period of protein release was longer than that of SA and continued protein release was observed even after the microsphere matrix had completely degraded. Differential scanning calorimetric studies demonstrated an interaction between protein and the FAD monomers produced with microsphere degradation. It is likely that the protein interaction with FAD monomers permits formation of water-insoluble protein aggregates which slowly dissolve and diffuse out of the matrix, leading to delayed protein release. For trypsin-loaded microspheres, trypsin lost 40% of its activity during microsphere preparation. Activity studies demonstrated that the sonication process was primarily responsible for activity loss. A reduction in the period of ultrasound exposure decreased the loss of protein activity to around 20%.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Tabata Y,Gutta S,Langer Rdoi
10.1023/a:1018929531410subject
Has Abstractpub_date
1993-04-01 00:00:00pages
487-96issue
4eissn
0724-8741issn
1573-904Xjournal_volume
10pub_type
杂志文章abstract:PURPOSE:Multidrug and toxin extrusion proteins (MATEs) are multispecific organic cation transporters mediating the efflux of various cationic drugs into the urine. The present study aimed at identifying endogenous compounds in human plasma and urine specimens as biomarkers to evaluate drug interactions involving MATEs ...
journal_title:Pharmaceutical research
pub_type: 临床试验,杂志文章
doi:10.1007/s11095-013-1144-y
更新日期:2014-01-01 00:00:00
abstract:PURPOSE:(i) To use trehalose as a model compound to evaluate the concept of crystallinity in pharmaceuticals. (ii) To understand the structural nature of dehydrated trehalose dihydrate. MATERIALS AND METHODS:Trehalose dihydrate was dehydrated isothermally at several temperatures below 100 degrees C and the anhydrous p...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-006-9058-6
更新日期:2006-10-01 00:00:00
abstract:PURPOSE:We prepared injectable microspheres for controlled release of TAK-029, a water-soluble GPIIb/IIIa antagonist and discussed the characteristics of controlled release from microspheres. METHODS:Copoly(dl-lactic/glycolic)acid (PLGA) microspheres were used for controlled release of TAK-029 [4-(4-amidinobenzoylglyc...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1012190304074
更新日期:1997-09-01 00:00:00
abstract:PURPOSE:To evaluate the transcellular mechanism of novel enhancers absorption enhancement of human growth hormone (hGH), by examining the involvement of a P-glycoprotein-like efflux system, changes in membrane fluidity, and membrane damage. METHODS:Caco-2 cell monolayers were grown on Snapwell filter supports and plac...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1014809916407
更新日期:1999-08-01 00:00:00
abstract::Four lipophilic, low molecular weight drugs solubilized in phosphatidylcholine-bile salt mixed micelles were injected s.c. into the hind legs of sheep and their cumulative recoveries in lymph draining from the site of application were determined. Surprisingly, the cumulative recoveries (percentage of dose) varied betw...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015807913934
更新日期:1991-10-01 00:00:00
abstract:PURPOSE:Nasal delivery is a favorable route for vaccination against most respiratory infections, as antigen deposited in the nasal turbinate and Waldeyer's ring areas induce mucosal and systemic immune responses. However, little is known about the nasal distribution of the vaccines, specifically for infants. METHODS:A...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-020-02976-9
更新日期:2021-01-15 00:00:00
abstract:PURPOSE:To identify and quantify, in vitro and in vivo (in humans), the charge-carrying species during transdermal iontophoresis of lidocaine hydrochloride as a function of the concentration of drug relative to that of sodium chloride in the anodal solution. METHODS:In vitro experiments in standard diffusion cells qua...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1013370529366
更新日期:2001-12-01 00:00:00
abstract:PURPOSE:In vitro and in vivo permeation studies were conducted to evaluate the characteristic of percutaneous administration of high hydrophilic drug L-carnitine (LC) by Functional MicroArray (FMA) painless intradermal delivery system. METHODS:In vitro study was designed to assess the effects of various skins, donor c...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-010-0109-7
更新日期:2011-01-01 00:00:00
abstract::The effect of the penetration enhancers Azone, oleic acid, 1-dodecanol, dodecyl N,N-dimethylaminoacetate (DDAA), and dodecyl N,N-dimethylaminoisopropionate (DDAIP) on epithelial membrane lipids was examined using human buccal cell membranes as a model for epithelial lipid bilayer. Buccal epithelial cells (BEC) were la...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018919811227
更新日期:1994-02-01 00:00:00
abstract:PURPOSE:Desmopressin acetate (DDAVP) is used parenterally and intranasally in the control of several diseases. Oral administration of DDAVP, while most desirable, is not practical presently due to low bioavailability. The objective of the present study was to explore the feasibility for employing oil-in-water MucoAdhes...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016023111248
更新日期:1996-07-01 00:00:00
abstract:PURPOSE:Monocarboxylate transporter (MCT) inhibition represents a potential treatment strategy for γ-hydroxybutyric acid (GHB) overdose by blocking its renal reabsorption in the kidney. This study further evaluated the effects of a novel, highly potent MCT inhibitor, AR-C155858, on GHB toxicokinetics/toxicodynamics (TK...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-014-1583-0
更新日期:2015-06-01 00:00:00
abstract:PURPOSE:To develop a statistical model for predicting effect of food on the extent of absorption (area under the curve of time-plasma concentration profile, AUC) of drugs based on physicochemical properties. MATERIALS AND METHODS:Logistic regression was applied to establish the relationship between the effect of food ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9236-1
更新日期:2007-06-01 00:00:00
abstract:PURPOSE:The fate of inhaled salmon calcitonin (sCT) at the respiratory epithelial barrier was studied with particular emphasis on enzymatic degradation by trypsin, chymotrypsin, and neutrophil elastase. METHODS:Degradation of sCT was assessed by HPLC in cell homogenate, supernatant and intact monolayers of human respi...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-011-0553-z
更新日期:2012-01-01 00:00:00
abstract::Physiologically-based pharmacokinetic (PBPK) models explicitly incorporate tissue-specific blood flows, partition coefficients, and metabolic processes. Since PBPK models are derived using physiologic parameters and interactions of the compound with tissue components, these models are considered to be "bottom up" as o...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-016-2089-8
更新日期:2017-03-01 00:00:00
abstract::A physical-chemical analysis of the extent of sorption of water by tablets containing superdisintegrants was carried out following the aqueous film coating of formulated tablets. Characterization of the uncoated and coated tablet properties was conducted using thermogravimetric analysis, differential scanning calorime...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018932705370
更新日期:1993-08-01 00:00:00
abstract:PURPOSE:To better understand the nature of drug-excipient interactions we have studied the phase behavior of amorphous binary and ternary mixtures of citric acid, indomethacin and PVP, as model systems. METHODS:We have prepared amorphous mixtures by co-melting or coprecipitation from solvents, and have measured glass ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011983606606
更新日期:1998-08-01 00:00:00
abstract::At an ever increasing pace, synthetic biomaterials are being developed with specific functionalities for tissue engineering applications. These biomaterials possess properties including biocompatibility, mechanical strength, and degradation as well as functionalities such as specific cell adhesion and directed cell mi...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-008-9620-5
更新日期:2008-10-01 00:00:00
abstract:PURPOSE:To address the problem of precipitation of a poorly soluble drug during dissolution of highly soluble cocrystals by preparing granules intimately mixed with a water-soluble polymer. METHODS:Effectiveness of polymers as precipitation inhibitors during the dissolution of carbamazepine-nicotinamide (CBZ-NCT) cocr...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-019-2622-7
更新日期:2019-04-23 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:PURPOSE:To study the miscibility of proteins and polymer excipients in frozen solutions and freeze-dried solids as protein formulation models. METHODS:Thermal profiles of frozen solutions and freeze-dried solids containing various proteins (lysozyme, ovalbumin, BSA), nonionic polymers (Ficoll, polyvinylpyrrolidone [PV...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1026412107574
更新日期:2000-10-01 00:00:00
abstract:PURPOSE:To evaluate the potential for the acidic intestinal unstirred water layer (UWL) to induce drug supersaturation and enhance drug absorption from intestinal mixed micelles, via the promotion of fatty acid absorption. METHODS:Using a single-pass rat jejunal perfusion model, the absorptive-flux of cinnarizine and ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-013-1104-6
更新日期:2013-12-01 00:00:00
abstract:PURPOSE:The aim of this study was to test the ability of paclitaxel-loaded poly(butylcyanoacrylate) (PBCA) nanoparticles to overcome multidrug resistance (MDR) in human ovarian resistant cells (A2780/T) and investigate its possible mechanism. METHODS:We prepared paclitaxel-loaded PBCA nanoparticles by interfacial poly...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-010-0346-9
更新日期:2011-04-01 00:00:00
abstract:PURPOSE:Changes in drug absorption and first-pass metabolism have been reported throughout the pediatric age range. Our aim is to characterize both intestinal and hepatic CYP3A-mediated metabolism of midazolam in children in order to predict first-pass and systemic metabolism of CYP3A substrates. METHODS:Pharmacokinet...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-018-2458-6
更新日期:2018-07-30 00:00:00
abstract:PURPOSE:To examine the transport characteristics of the multidrug resistance-associated protein (MRP) substrate fluorescein across the isolated rat small intestinal segments. METHODS:The transport of fluorescein was studied in side-by-side diffusion chambers under short-circuited conditions at physiological pH. RESUL...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/b:pham.0000022410.89709.c3
更新日期:2004-04-01 00:00:00
abstract::The technique of Affinity capillary electrophoresis (ACE) is a useful tool to characterize complexation and partition equilibria. A wide range of applications in pharmaceutics has been presented: the determination of pKA values, of association constants between drugs and cyclodextrins or amphiphilic compounds as well ...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:
更新日期:1999-11-01 00:00:00
abstract:PURPOSE:The organic cation transporters (OCTs) and multidrug and toxin extrusions (MATEs) together are regarded as an organic cation transport system critical to the disposition and response of many organic cationic drugs. Patient response to the analgesic morphine, a characterized substrate for human OCT1, is highly v...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-018-2526-y
更新日期:2018-10-25 00:00:00
abstract:PURPOSE:The purpose of this study is to investigate the characteristics of pGlu-L-Dopa-Pro as a prodrug of L-Dopa. METHODS:pGlu-L-Dopa-Pro and L-Dopa-Pro were synthesized using the standard procedures of peptide synthesis. The conversion of pGlu-L-Dopa-Pro to L-Dopa was studied using pyroglutamyl aminopeptidase I and ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016239321494
更新日期:1995-07-01 00:00:00
abstract:PURPOSE:To characterize factor(s) contained in apical medium of primary cultured rat alveolar epithelial type II cell-like monolayers (RAECM-II) that enhance insulin absorption across alveolar epithelial cells. MATERIALS AND METHODS:Primary rat alveolar epithelial cell monolayers cultured on Transwells in the presence...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9301-9
更新日期:2007-09-01 00:00:00
abstract:PURPOSE:To investigate the ability of various polymers to inhibit the crystallization of amorphous felodipine from amorphous molecular dispersions in the presence of absorbed moisture. METHODS:Spin coated films of felodipine with poly(vinylpyrrolidone) (PVP), hydroxypropylmethylcellulose acetate succinate (HPMCAS) and...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9331-3
更新日期:2008-04-01 00:00:00
abstract:PURPOSE:To determine the mechanism(s) by which effervescence induces penetration enhancement of a broad range of compounds ranging in size, structure, and other physiocochemical properties across rat and rabbit small intestinal epithelium. METHODS:Effervescent induced penetration enhancement was investigated in vitro ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011936901638
更新日期:1998-06-01 00:00:00