Abstract:
PURPOSE:The objective of this study was to develop and characterize long-circulating, biodegradable, and biocompatible nanoparticulate formulation as an intracellular delivery vehicle. METHODS:Poly(ethylene glycol) (PEG)-modified gelatin was synthesized by reacting Type-B gelatin with PEG-epoxide. The nanoparticles, prepared by pH and temperature controlled ethanol-water solvent displacement technique, were characterized for mean size, size distribution, and surface morphology. Electron spectroscopy for chemical analysis (ESCA) was used to confirm the surface presence of PEG chains. In vitro release of tetramethylrhodamine-labeled dextran (TMR-dextran, Mol. wt. 10,000 daltons) from the nanoparticle formulations was examined in PBS, with and without 0.2-mg/ml protease, at 37 degrees C. Relative cytotoxicity profile of control and PEGylated gelatin was evaluated in BT-20 a human breast cancer cell line. The nanoparticles were incubated with BT-20 cells to determine uptake and cellular distribution using confocal microscopy. RESULTS:Gelatin and PEGylated gelatin nanoparticles were found to be spherical in shape with a smooth surface in a size range of 200-500 nm and a unimodal size distribution. ESCA results showed an increase in the ether carbon (-C-O-) peak in the PEGylated gelatin nanoparticles due to the presence of PEG chains. The presence of PEG chains decreased the percent release of TMR-dextran in the presence of proteolytic enzyme due to steric repulsion. Cytotoxicity assays indicated that both gelatin and PEGylated gelatin were completely non-toxic to the cells. A large fraction of the administered control gelatin and PEGylated gelatin nanoparticles were found to be concentrated in the perinuclear region of the BT-20 cells after 12 hours indicating possible vesicular transport through initial uptake by endocytosis and endosomal processing. CONCLUSION:The results of this study show that PEGylation of gelatin may prove beneficial as long-circulating delivery system in vivo. Additionally, the nanoparticles could encapsulate hydrophilic macromolecules and are internalized by tumor cells.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Kaul G,Amiji Mdoi
10.1023/a:1016486910719subject
Has Abstractpub_date
2002-07-01 00:00:00pages
1061-7issue
7eissn
0724-8741issn
1573-904Xjournal_volume
19pub_type
杂志文章abstract:PURPOSE:The sensitivity and effectiveness of indirect metrics proposed for the assessment of comparative absorption rates in bioequivalence studies [Cmax, Tmax, partial AUC (AUCp), feathered slope (SLf), intercept metric (I)] were originally tested by assuming first-order absorption. The present study re-evaluates thei...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1007521016985
更新日期:2000-05-01 00:00:00
abstract::The interdependent relationship between pharmacology and toxicology is fundamental to the concepts of efficacy and safety of both drugs and xenobiotics. The traditional concept of establishing efficacious and tolerated doses to define a 'therapeutic window' appears simplistic in the context of an exponentially increas...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-014-1415-2
更新日期:2014-09-01 00:00:00
abstract:PURPOSE:To determine whether LHRH-receptor is expressed in Calu-3, a human bronchial epithelial cell line, and to further determine whether this receptor plays a role in the transport of deslorelin, an LHRH agonist. METHODS:Using cultured monolayers of Calu-3 grown at air-interface, the presence and localization of LH...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/b:pham.0000029294.70707.74
更新日期:2004-06-01 00:00:00
abstract:PURPOSE:To develop a new technique, spray freeze drying, for preparing protein aerosol powders. Also, to compare the spray freeze-dried powders with spray-dried powders in terms of physical properties and aerosol performance. METHODS:Protein powders were characterized using particle size analysis, thermogravimetric an...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018828425184
更新日期:1999-02-01 00:00:00
abstract:PURPOSE:To study the reaction of artelinic acid with chemical model systems of cytochrome P-450 as a means of obtaining authentic samples of the putative metabolites necessary for identification of the mammalian metabolites of artelinic acid. METHODS:Artelinic acid was reacted with different organic complexes of iron(...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1012185124972
更新日期:1997-10-01 00:00:00
abstract:PURPOSE:The pharmacokinetics, analgesic efficacy, and irritancy potential of Buprederm, a new transdermal delivery system of buprenorphine, was evaluated. METHODS:Single and multiple dose pharmacokinetic studies were conducted in mice and rabbits. The analgesic efficacy and skin irritation potential were determined by...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9470-6
更新日期:2008-05-01 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:PURPOSE:To characterize the pharmacokinetic/pharmacodynamic (PK/PD) properties of a new polyethylene glycol (PEG) conjugate formulation of interferon (IFN)-beta la following subcutaneous (SC) administration in monkeys. METHODS:Single SC injections of 0.3, 1, and 3 million international units (MIU)/kg of PEG-IFN-beta 1...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-004-9009-z
更新日期:2005-01-01 00:00:00
abstract:PURPOSE:The in vitro inhibitory effect of Docetaxel (DTX) and Everolimus (EVR) alone and together in poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-b-PLA) nanocarriers on angiogenic processes and acute toxicity in mice was evaluated. METHODS:PEG-b-PLA DTX and/or EVR nanocarriers were characterized for size, dr...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-013-1188-z
更新日期:2014-03-01 00:00:00
abstract:PURPOSE:Since glomerular filtration rate (GFR) is responsible for the elimination of a large number of water-soluble drugs, the aim of this study was to develop a semi-physiological function for GFR maturation from neonates to adults. METHODS:In the pharmacokinetic analysis (NONMEM VI) based on data of gentamicin, tob...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-014-1361-z
更新日期:2014-10-01 00:00:00
abstract:PURPOSE:To demonstrate the applicability of thermally stimulated current (TSC) spectrometry for the detection of low levels of the amorphous phase in crystalline pharmaceutical materials. METHODS:A crystalline drug substance was melt quenched to produce an amorphous material. Blends of the crystalline and amorphous ph...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011087012826
更新日期:2001-01-01 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:The objective of this work is to understand the sequence specificity of HAV peptides and to improve their selectivity in regulating E-cadherin-E-cadherin interactions in the intercellular junctions. METHODS:Peptide 1 was modified using an alanine scanning method to give peptides 2-6. The ability of these pepti...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011094025008
更新日期:2001-04-01 00:00:00
abstract::A procedure is described that is suitable for the radioimmunoassay (RIA) of 9-[(l,3-dihydroxy-2-propoxy)-methyl]guanine (DHPG) in plasma or serum at concentrations as low as 0.7 ng/ml (2.75 × 10(-9) M). Antiserum was prepared by coupling DHPG monohemisuccinate to bovine serum albumin and immunizing rabbits with the re...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/A:1016397520991
更新日期:1986-04-01 00:00:00
abstract:PURPOSE:To evaluate the impact of intestinal first-pass metabolism (Fg) by cytochrome P4503A (CYP3A) and uridine 5'-diphosphate-glucuronosyltransferases (UGT) on in vivo oral absorption of their substrate drugs. METHODS:CYP3A and UGT substrates were orally administered to portal-vein cannulated (PV) rats to evaluate t...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-014-1489-x
更新日期:2015-02-01 00:00:00
abstract:PURPOSE:It was the purpose of this study to develop a new oral drug delivery system for low molecular weight heparin (LMWH) providing an improved bioavailability and a prolonged therapeutic effect. METHODS:The permeation enhancing polycarbophil-cysteine conjugate (PCP-Cys) used in this study displayed 111.4 +/- 6.4 mi...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1023803706746
更新日期:2003-06-01 00:00:00
abstract:PURPOSE:Scutellarin, a flavonoid derived from the plant Erigeron breviscapus, is currently widely used to treat cerebrovascular diseases, liver-related diseases, and hyperlipidemia in china and other East Asian countries. This study was to investigate the effect of scutellarin on the uptake of rosuvastatin in HEK293T c...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-020-02950-5
更新日期:2020-10-29 00:00:00
abstract:PURPOSE:To prepare a thermoreversible gel system able to work as a medium for crystallization at around 20°C, allowing easy retrieval of crystals by simply decreasing the gel temperature. Lactose was selected has model substance for crystallization. METHODS:Water solutions with different% of poloxamer 407, α-Lactose m...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-011-0606-3
更新日期:2012-03-01 00:00:00
abstract::Solution calorimetry has been employed to evaluate the stability constants and enthalpy changes associated with complex formation between alpha-, beta, or gamma-cyclodextrin (CD) and a group of amine compounds having the diphenylmethyl functionality. Data from thermal titrations of the compounds were analyzed using no...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015880218535
更新日期:1991-07-01 00:00:00
abstract:PURPOSE:To investigate plasmid DNA interactions with liposomes prepared from dimyristoylglyceroethylphosphocholine (EDMPC) and DOPE using high sensitivity differential scanning calorimetry (HSDSC). MATERIALS AND METHODS:Large unilamellar liposomes of EDMPC with DOPE (mol ratio 0-50%) were prepared. Plasmid DNA was add...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9325-1
更新日期:2007-10-01 00:00:00
abstract:PURPOSE:To develop a new bionic system from an existing drug dissolution/absorption simulating system (DDASS) to simultaneously predict the release and absorption of enteric-coated formulations. METHODS:In accordance with the pH-dependent characteristics of enteric-coated formulations, the modified DDASS was designed ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0905-3
更新日期:2013-02-01 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::A rapid quantitative, enantioselective HPLC method for the analysis of the four stereoisomers, (+) and (-) erythro and (+) and (-) threo forms, of mefloquine has been developed using a Chiralpak Ad analytical column containing amylose tris-3,5-dimethylphenyl carbonate coated on silica gel and hexane/ethanol/diethylami...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015832912774
更新日期:1992-12-01 00:00:00
abstract:PURPOSE:The goal of this investigation was to demonstrate whether the intrinsic flux of a drug diffusing across a membrane mounted in a flow-through diffusion cell may be accurately and easily determined by accounting for the accumulation in the receiver chamber. METHODS:Mathematical modeling, applied to transdermal d...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016216611809
更新日期:1995-12-01 00:00:00
abstract::Pharmacokinetic-pharmacodynamic modeling algorithms, in general, rely on hysteresis minimization techniques that assume time-invariant pharmacodynamics (constant biophase concentration-effect relationships). When time-variant pharmacodynamics are observed, a specific model for tolerance or sensitization is required. H...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018940122382
更新日期:1994-12-01 00:00:00
abstract:PURPOSE:Pluronics are known as inhibitors of multidrug resistance thus making tumor cells sensitive to therapeutic doses of drugs. The purpose of our study consists in revealing molecular targets of the hydrophobic poly(propylene oxide) block of pluronics in living cells and the dependence of the polymers chemosensitiz...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-018-2484-4
更新日期:2018-09-06 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: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:PURPOSE:The objective of this study was to investigate the possible influence of probenecid on morphine transport across the blood-brain barrier (BBB) in rats. METHODS:Microdialysis probes, calibrated using retrodialysis by drug, were placed into the striatum and jugular vein of seven Sprague-Dawley rats. Morphine was...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1023250900462
更新日期:2003-04-01 00:00:00
abstract:PURPOSE:An in vitro dynamic pharmacokinetic (PK) cell culture system was developed to more precisely simulate physiologic nanoparticle/drug exposure. METHODS:A dynamic PK cell culture system was developed to more closely reflect physiologic nanoparticle/drug concentrations that are changing with time. Macrophages were...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-019-2576-9
更新日期:2019-02-01 00:00:00