Abstract：
PURPOSE:Paclitaxel is active and widely used to treat multiple types of solid tumors. The commercially available paclitaxel formulation uses Cremophor/ethanol (C/E) as the solubilizers. Other formulations including nanoparticles have been introduced. This study evaluated the effects of nanoparticle formulation of paclitaxel on its tissue distribution. METHODS:We compared the plasma and tissue pharmacokinetics of paclitaxel-loaded gelatin nanoparticles and the C/E formulation. Mice were given paclitaxel-equivalent doses of 10 mg/kg by intravenous injection. RESULTS:The nanoparticle and C/E formulations showed significant differences in paclitaxel disposition; the nanoparticles yielded 40% smaller area under the blood concentration-time curve and faster blood clearance of total paclitaxel concentrations (sum of free, protein-bound, and nanoparticle-entrapped drug). The two formulations also showed different tissue specificity. The rank order of tissue-to-blood concentration ratios was liver > small intestine > kidney > large intestine > spleen = stomach > lung > heart for the nanoparticles, and liver > small intestine > large intestine > stomach > lung > or = kidney > spleen > heart for the C/E formulation. The nanoparticles also showed longer retention and higher accumulation in organs and tissues (average of 3.2 +/- 2.3-fold), especially in the liver, small intestine, and kidney. The most striking difference was an 8-fold greater drug accumulation and sustained retention in the kidney. CONCLUSIONS:These data indicate that formulation of paclitaxel affects its clearance and distribution into tissues, with preferential accumulation of nanoparticles in the liver, spleen, small intestine, and kidney.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Yeh TK,Lu Z,Wientjes MG,Au JLdoi
10.1007/s11095-005-4581-4subject
Has Abstractpub_date
2005-06-01 00:00:00pages
867-74issue
6eissn
0724-8741issn
1573-904Xjournal_volume
22pub_type
杂志文章abstract：PURPOSE:Formulate phospho-sulindac (P-S, OXT-328) in a Pluronic hydrogel to be used as a topical anti-inflammatory agent and study its efficacy, safety and pharmacokinetics in an arthritis model. METHODS:LEW/crlBR rats with Freund's adjuvant-induced arthritis were treated with P-S formulated in Pluronic hydrogel (PSH)...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0953-8
更新日期：2013-06-01 00:00:00
abstract：PURPOSE:Carboxylesterases are important in the detoxification of drugs, pesticides and other xenobiotics. This study was to evaluate a series of substrates and inhibitors for characterizing these enzymes. METHODS:A series of novel aliphatic esters and thioesters were used in spectral assays to monitor human, murine an...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016071311190
更新日期：1996-10-01 00:00:00
abstract：PURPOSE:SN-38, a potent chemotherapeutic drug, has not been used clinically because of its severe side effects and poor solubility. In this work, we aimed to evaluate the effect of dose and multiple injections of SN-38-loaded polymeric depots on antitumor efficacy and toxicity in vivo. METHODS:Preparation and characte...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-2011-4
更新日期：2016-12-01 00:00:00
abstract：PURPOSE:Relatively large (>5 microm) and porous (mass density <0.4 g/cm3) particles present advantages for the delivery of drugs to the lungs, e.g., excellent aerosolization properties. The aim of this study was, first, to formulate such particles with excipients that are either FDA-approved for inhalation or endogenou...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018910200420
更新日期：1999-11-01 00:00:00
abstract：PURPOSE:To investigate the underlying cause for the observed differences in self-associating and viscoelastic behavior between two monoclonal antibodies, MAb1, and MAb2. METHODS:Several mutants were designed by swapping charged residues in MAb1 with those present in MAb2 at their respective positions and vice versa. R...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0410-0
更新日期：2011-07-01 00:00:00
abstract：:The release of lithium carbonate incorporated into polymethylmethacrylate, polyvinyl chloride, hydrogenated vegetable oil, and carbomer matrix tablets was studied in vitro. The formulation containing 10% carbomer showed a sustained-release profile comparable to that of a standard, commercially available, sustained-rel...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015863204732
更新日期：1990-04-01 00:00:00
abstract：PURPOSE:To assess the efficacy of the novel clinical formulation of fenretinide (LAU-7b) for the treatment of allergic asthma. To study the association between LAU-7b treatment in allergic asthma and the modulation of very long chain ceramides (VLCC). METHODS:We used two allergens (OVA and HDM) to induce asthma in mou...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-019-2743-z
更新日期：2020-01-08 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:Biomaterials which release locally high concentrations of antithrombotic agents should lessen the thrombogenicity of the materials. To evaluate this approach, we prepared novel polyurethane matrices loaded with hirudin and coated them with 2-hydroxyethyl methacrylate (HEMA) by glow discharge plasma deposition (...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011987423502
更新日期：1998-05-01 00:00:00
abstract：PURPOSE:Grapefruit juice (GJ) is known to increase the oral bioavailability of many CYP3A-substrates by inhibiting intestinal phase-I metabolism. However, the magnitude of AUC increase is often insignificant and highly variable. Since we earlier suggested that CYP3A and P-glycoprotein (P-gp) form a concerted barrier to...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011902625609
更新日期：1999-04-01 00:00:00
abstract：PURPOSE:Critical steps in the subcellular processing of poly(ethylene imine)/nucleic acid complexes, especially endosomal/lysosomal escape, were visualized by using living cell confocal laser scanning microscopy (CSLM) to obtain an insight into their mechanism. METHODS:Living cell confocal microscopy was used to exami...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1014212630566
更新日期：2002-02-01 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:The objective of this study was to elucidate the different mechanisms of action of different excipients on the oxidation of Met1, Met122, Met127, and Met138 in granulocyte colony-stimulating factor (G-CSF) by using hydrogen peroxide as the oxidant. METHODS:The oxidation of Met1, Met127, and Met138 was quantifi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-004-9019-x
更新日期：2005-01-01 00:00:00
abstract：PURPOSE:To elucidate the catalytic mechanism of the esterase-like activity of serum albumin (SA), the reactivity of SA from six species was investigated using p-nitrophenyl esters as model substrates. METHODS:The effect of pH and the energetic and thermodynamic profiles of SA were determined for all species for p-nitr...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000016241.84630.06
更新日期：2004-02-01 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:The objective of this investigation was to determine, using the Caco-2 cell culture model, the extent to which the paracellular and transcellular routes contributed to the transport of passively absorbed drugs. An effort was also made to determine the controlling factors in this process. METHODS:We selected a ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012111008617
更新日期：1997-09-01 00:00:00
abstract：PURPOSE:The cause of antibody positive pure red cell aplasia associated with the subcutaneous administration of EPREX to patients with chronic kidney failure has been determined to be due to the leaching of weakly adjuvant compounds from the uncoated rubber stoppers that were formerly used in prefilled syringes. Other ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-5356-7
更新日期：2005-07-01 00:00:00
abstract：PURPOSE:We describe the AERX aerosol delivery system, a new, bolus inhalation device that is actuated at preprogrammed values of inspiratory flow rate and inhaled volume. We report on its in vitro characterization using a particular set of conditions used in pharmacokinetic and scintigraphic studies. METHODS:Multiple ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012058323754
更新日期：1997-03-01 00:00:00
abstract：:A method for determination of absorption rate and bioavailability was developed to reduce the influence of intraindividual variability and applied to the absolute intraperitoneal availability of lithium in the rat. In this method the test and the reference doses are given with a few hours' interval, and the resulting ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015939917646
更新日期：1989-09-01 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：PURPOSE:A series of studies was conducted to evaluate the preclinical pharmacokinetics of SB-239063 (trans-1-(4-hydroxycyclohexyl)-4-(4-fluorophenyl)-5-[(2-methoxy)pyrimidin-4-yl] imidazole), a potent and selective p38 MAP kinase inhibitor. METHODS:SB-239063 was administered both i.v. and p.o. in the rat, dog, cynomol...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1013002414678
更新日期：2001-09-01 00:00:00
abstract：:Nanotechnology has continuously contributed to the fast development of diagnostic and therapeutic agents. Theranostic nanomedicine has encompassed the ongoing efforts on concurrent molecular imaging of biomarkers, delivery of therapeutic agents, and monitoring of therapy response. Among these formulations, polymer-bas...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-013-1103-7
更新日期：2014-06-01 00:00:00
abstract：:Gene delivery vectors based on adeno-associated virus (AAV) are highly promising due to several desirable features of this parent virus, including a lack of pathogenicity, efficient infection of dividing and non-dividing cells, and sustained maintenance of the viral genome. However, several problems should be addresse...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-007-9431-0
更新日期：2008-03-01 00:00:00
abstract：:Using brine shrimp lethality to direct fractionation, extracts of the bark of Annona bullata Rich. (Annonaceae) have yielded 16 alpha-hydroxy-(-)-kauranoic acid as a bioactive plant constituent. This previously known diterpene showed significant (ED50 8.25 x 10(-2) micrograms/ml) and selective cytotoxicity against A-5...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015819422479
更新日期：1990-04-01 00:00:00
abstract：:Various derivatives of the C-terminal amide group in N-protected amino acid and peptide amides were synthesized to assess their suitability as prodrug forms with the aim of protecting the amide or peptide bond against cleavage by alpha-chymotrypsin. Whereas N-acetylation, N-hydroxymethylation, and N-phthalidylation di...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015854718903
更新日期：1991-12-01 00:00:00
abstract：PURPOSE:Percutaneous absorption assays of molecules for pharmaceutical and cosmetology purposes are important to determine the bioavailability of new compounds, once topically applied. The current method of choice is to measure the rate of diffusion through excised human skin using a diffusion cell. This method however...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1654-x
更新日期：2015-08-01 00:00:00
abstract：:Molecular dynamics simulations and the generation of ad hoc chemical libraries are playing an increasingly important and recognized role in structure-based virtual screening. These approaches are important for treating target flexibility and improving the drug discovery pipeline. In this article I will comment on thes...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1012-9
更新日期：2013-05-01 00:00:00
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 reacte...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018908421434
更新日期：1999-07-01 00:00:00
abstract：PURPOSE:A double-mutant E224A/E262A full-length botulinum neurotoxin (BoNT) Type A with structural similarity to native BoNT/A but lacking the endopeptidase activity provides an ideal surrogate for testing pharmacokinetics and immunochemical characteristics of BoNT. METHODS:We determined lethality (LD50) of deactivate...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1816-x
更新日期：2016-03-01 00:00:00
abstract：PURPOSE:The aim of the study is to determine the effect of experimental parameters on microinfusion through hollow microneedles into skin to optimize drug delivery protocols and identify rate-limiting barriers to flow. METHODS:Glass microneedles were inserted to a depth of 720-1080 microm into human cadaver skin to mi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-8498-8
更新日期：2006-01-01 00:00:00
