Abstract:
PURPOSE:Doxorubicin was chemically conjugated to a terminal end group of poly(D,L-lactic-co-glycolic acid) [PLGA] and the doxorubicin-PLGA conjugate was formulated into nanoparticles to sustain the release of doxorubicin. METHODS:A hydroxyl terminal group of PLGA was activated by p-nitrophenyl chloroformate and reacted with a primary amine group of doxorubicin for conjugation. The conjugates were fabricated into ca. 300 nm size nanoparticles by a spontaneous emulsion-solvent diffusion method. The amount of released doxorubicin and its PLGA oligomer conjugates was quantitated as a function of time. The cytotoxicity of the released species was determined using a HepG2 cell line. RESULTS:Loading efficiency and loading percentage of doxorubicin-PLGA conjugate within the nanoparticles were 96.6% and 3.45 (w/w) %, respectively while those for unconjugated doxorubicin were 6.7% and 0.26 (w/w) %, respectively. Both formulation parameters increased dramatically due to the hydrophobically modified doxorubicin by the conjugation of PLGA. The nanoparticles consisting of the conjugate exhibited sustained release over 25 days, whereas those containing unconjugated free doxorubicin showed rapid doxorubicin release in 5 days. A mixture of doxorubicin and its PLGA oligomer conjugates released from the nanoparticles had comparable IC50 value in a HepG2 cell line compared to that of free doxorubicin. Sustained drug release was attributed to the chemical degradation of conjugated PLGA backbone, which permitted water solubilization and subsequent release of doxorubicin conjugated PLGA oligomers into the medium. CONCLUSIONS:The conjugation approach of doxorubicin to PLGA was potentially useful for nanoparticle formulations that require high drug loading and sustained release. The doxorubicin-PLGA oligomer conjugate released in the medium demonstrated a slightly lower cytotoxic activity than free doxorubicin in a HepG2 cell line.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Yoo HS,Oh JE,Lee KH,Park TGdoi
10.1023/a:1018908421434subject
Has Abstractpub_date
1999-07-01 00:00:00pages
1114-8issue
7eissn
0724-8741issn
1573-904Xjournal_volume
16pub_type
杂志文章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::Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring anti-inflammatory antagonist of interleukin-1 family of pro-inflammatory cytokines. The broad spectrum anti-inflammatory effects of IL-1Ra have been investigated against various auto-immune diseases such as diabetes mellitus, rheumatoid arthritis. Des...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-013-1118-0
更新日期:2013-11-01 00:00:00
abstract:PURPOSE:To compare the ability of alkyl-aryl isothiocyanates (ITCs) to increase the activities of the Phase 2 detoxification enzymes NAD[P]H:quinone acceptor oxidoreductase 1 (NQO1) and glutathione S-transferases (GST) in rat tissues in vivo and in cells in vitro. MATERIALS AND METHODS:Twelve alkyl-aryl ITCs and the f...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-008-9595-2
更新日期:2008-09-01 00:00:00
abstract:PURPOSE:The major objectives of this study were to 1) develop a new mathematical model describing all phases of drug release from bioerodible microparticles; 2) evaluate the validity of the theory with experimental data; and 3) use the model to elucidate the release mechanisms in poly(lactide-co-glycolide acid)-based m...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1021457911533
更新日期:2002-12-01 00:00:00
abstract:PURPOSE:A mechanism-based PK-PD model was developed to predict the time course of dopamine D(2) receptor occupancy (D(2)RO) in rat striatum following administration of olanzapine, an atypical antipsychotic drug. METHODS:A population approach was utilized to quantify both the pharmacokinetics and pharmacodynamics of ol...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-011-0477-7
更新日期:2011-10-01 00:00:00
abstract:PURPOSE:To evaluate the potential of ascorbate as a novel ligand in the preparation of pharmaceutical nanocarriers with enhanced tumor-cell specific binding and cytotoxicity. METHODS:Palmitoyl ascorbate was incorporated into liposomes at varying concentrations. A stable formulation was selected based on size and zeta ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-008-9674-4
更新日期:2008-11-01 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::The three-dimensional structures and molecular electrostatic potentials of the cis(Z) and trans(E)-isomers of flupenthixol and clopenthixol were examined by computer graphics and molecular mechanical and quantum mechanical calculations, and their internal molecular motions were studied by molecular dynamics simulation...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015842926345
更新日期:1991-04-01 00:00:00
abstract:PURPOSE:Nonlinear conjugation metabolic rate of valproic acid (VPA) has been speculated previously from plasma elimination and liver concentration of VPA in guinea pigs. The purposes of the present study were to assess our speculation by direct measurement of VPA glucuronidation rate in vitro. METHODS:VPA at various c...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016028707130
更新日期:1996-08-01 00:00:00
abstract::The influence of the jejunal bloodflow on the absorption of theophylline was investigated. The bloodflow through a segment under investigation was varied by changing the systemic blood pressure by means of a donor blood infusion into the jugular vein or by an infusion of isoprenaline or levarterenol into a femoral vei...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/A:1016374508542
更新日期:1984-01-01 00:00:00
abstract:PURPOSE:Nanocrystalline drug-polymer dispersions are of significant interest in pharmaceutical delivery. The purpose of this work is to demonstrate the applicability of methods based on two-dimensional (2D) and multinuclear solid-state NMR (SSNMR) to a novel nanocrystalline pharmaceutical dispersion of ebselen with pol...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0713-9
更新日期:2012-07-01 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 explore the application of scanning ion occlusion sensing (SIOS) as a novel technology for characterization of nanoparticles. METHODS:Liposomes were employed as model nanoparticles. The size distribution of the liposomes was measured by both SIOS and dynamic light scattering (DLS). Particle number concentra...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0788-3
更新日期:2012-09-01 00:00:00
abstract::A new enteric-coated formulation of sodium ursodeoxycholate was prepared and administered to man. The barrier film disintegrates and releases the drug only at pH > or = 5.5. The sodium salt of glycoursodeoxycholate was also prepared and encapsulated like ursodeoxycholate. Serum levels of ursodeoxycholate and glycourso...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018907825281
更新日期:1994-05-01 00:00:00
abstract:PURPOSE:Cationic liposomes are expected to be useful as nonviral vectors for gene delivery. Cationic liposomes showed cytotoxicity, and we proposed that the cytotoxicity is through apoptosis. In this study, we examined the effects of liposomal properties, such as liposomal charge, size, membrane fluidity, and PEG coati...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1024441702398
更新日期:2003-07-01 00:00:00
abstract:PURPOSE:To study the role of unsaturated fatty acid ester substituents in the autoxidation of polysorbate 80 using quantitative kinetics. METHODS:Oxidation kinetics were monitored at 40 degrees C in aqueous solution by tracking head space oxygen consumption using a fiber optic oxygen sensor with phase shift fluorescen...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-009-9946-7
更新日期:2009-10-01 00:00:00
abstract:PURPOSE:Performance of a transdermal delivery system (TDS) can be affected by exposure to elevated temperature, which can lead to unintended safety issues. This study investigated TDS and skin temperatures and their relationship in vivo, characterized the effective thermal resistance of skin, and identified the in vitr...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-017-2171-x
更新日期:2017-07-01 00:00:00
abstract:PURPOSE:The possibility of preparing nanoparticles in the supercooled thermotropic liquid crystalline state from cholesterol esters with saturated acyl chains as well as the incorporation of model drugs into the dispersions was investigated using cholesteryl myristate (CM) as a model cholesterol ester. METHODS:Nanopar...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/b:pham.0000045237.46019.6e
更新日期:2004-10-01 00:00:00
abstract::The effects of tertiary amine-containing basic drugs on the enzymes located in the mitochondria and the effect of monoamine oxidase inhibitors (MAOIs) on drug accumulation in lung mitochondria have been studied. Various basic drugs inhibited MAO activity but not other mitochondrial marker enzymes. The potency of MAO i...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015964623098
更新日期:1989-10-01 00:00:00
abstract:PURPOSE:The objective of this study was to develop and evaluate a pulsatile drug delivery system based on an impermeable capsule body filled with drug and an erodible plug placed in the opening of the capsule body. METHODS:The erodible plugs were either prepared by direct compression followed by placing the tablets in...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011940718534
更新日期:1998-03-01 00:00:00
abstract:PURPOSE:The present investigation describes a formulative study for the development of innovative drug delivery systems for bromocriptine. METHODS:Solid lipid nanoparticles (SLN) based on different lipidic components have been produced and characterized. Morphology and dimensional distribution have been investigated b...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9514-y
更新日期:2008-07-01 00:00:00
abstract:PURPOSE:The purpose of this study was to assess the antifungal activity and renal and hepatic toxicity of amphotericin B (AmpB) following administration of Fungizone (FZ) and a heat-treated form of FZ (HFZ) to rats infected with Aspergillus fumigatus. METHODS:Infected rats were administered FZ and HFZ at a dosing regi...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/b:pham.0000041449.46054.b4
更新日期:2004-09-01 00:00:00
abstract:PURPOSE:Poly-L-arginine (PLA) enhances the paracellular permeability of the Caco-2 cell monolayer to hydrophilic macromolecules by disappearance of tight junction (TJ) proteins from cell-cell junctions. However, the mechanism of the disappearance of TJ proteins in response to PLA has been unclear. In this study, we inv...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-014-1324-4
更新日期:2014-09-01 00:00:00
abstract:PURPOSE:To investigate the influence of nanocarrier molecular size and shape on breast duct retention in normal rats using a non-invasive optical imaging method. METHODS:Fluorescein-labeled PEG nanocarriers of different molecular weights and shapes (linear, two-arm, four-arm, and eight-arm) were intraductally administ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0763-z
更新日期:2012-09-01 00:00:00
abstract:PURPOSE:Platinum-based therapies are the first line treatments for most types of cancer including ovarian cancer. However, their use is associated with dose-limiting toxicities and resistance. We report initial translational studies of a theranostic nanoemulsion loaded with a cisplatin derivative, myrisplatin and pro-a...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-015-1660-z
更新日期:2015-08-01 00:00:00
abstract:PURPOSE:It was the aim of this study to synthesize and characterize a novel chitosan-glutathione (GSH) conjugate providing improved mucoadhesive and permeation-enhancing properties. METHODS:Mediated by carbodiimide and N-hydroxysuccinimide, glutathione was covalently attached to chitosan via the formation of an amide ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-005-6248-6
更新日期:2005-09-01 00:00:00
abstract:PURPOSE:In this study, we aimed to illustrate the utility of fractional radiofrequency (RF) that generated microchannels in the skin, allowing delivery of peptide and siRNA via the skin. The mechanisms involved in the correlation between macromolecule permeation and skin structure were also elucidated. METHODS:The mor...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-014-1568-z
更新日期:2015-05-01 00:00:00
abstract::To clarify the mechanism by which basic drugs accumulate in the lung, the binding selectivity of drugs to different subcellular structures of the perfused rat lung was examined. Imipramine, quinine, and metoclopramide were used as examples of basic drugs. The accumulation of basic drugs was highest in the mitochondria...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016481911538
更新日期:1987-02-01 00:00:00
abstract:PURPOSE:Adenoviruses are being developed for diseases of the gastrointestinal tract. Several in vitro assays were used to predict stability of PEGylated adenovirus along the GI tract and determine in vivo gene transfer after oral administration. METHODS:Recombinant adenovirus was modified with monomethoxypoly(ethylene...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1025714412337
更新日期:2003-09-01 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