Abstract：
PURPOSE:A key step of delivering extracellular agents to its intracellular target is to escape from endosomal/lysosomal compartments, while minimizing the release of digestive enzymes that may compromise cellular functions. In this study, we examined the intracellular distribution of both fluorecent cargoes and enzymes by a particle delivery platform made from the controlled blending of poly(lactic-co-glycolic acid) (PLGA) and a random pH-sensitive copolymer. METHODS:We utilized both microscopic and biochemical methods to semi-quantitatively assess how the composition of blend particles affects the level of endosomal escape of cargos of various sizes and enzymes into the cytosolic space. RESULTS:We demonstrated that these polymeric particles enabled the controlled delivery of cargos into the cytosolic space that was more dependent on the cargo size and less on the composition of blend particles. Blend particles did not induce the rupture of endosomal/lysosomal compartments and released less than 20% of endosomal/lysosomal enzymes. CONCLUSIONS:This study provides insight into understanding the efficacy and safety of a delivery system for intracellular delivery of biologics and drugs. Blend particles offer a potential platform to target intracellular compartments while potentially minimizing cellular toxicity.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Zhan X,Tran KK,Wang L,Shen Hdoi
10.1007/s11095-015-1619-0subject
Has Abstractpub_date
2015-07-01 00:00:00pages
2280-91issue
7eissn
0724-8741issn
1573-904Xjournal_volume
32pub_type
杂志文章abstract：:Moexipril [2-[(1-ethoxycarbonyl)-3-phenylpropyl]amino-1-oxopropyl]-6, 7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (S,S,S)], an ester prodrug of an ACE inhibitor, was formulated in controlled-release preparations with a range of in vitro release rates, to provide a prolonged input of drug in vivo. Howe...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015919413103
更新日期：1989-09-01 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：PURPOSE:To develop a non-viral gene delivery system in the form of an oil-in-water (o/w) lipid emulsion. METHOD:Cationic lipid emulsions were formulated with soybean oil, 1,2-dioleoyl-sn-glycero-3-trimethylammonium-propane (DOTAP) as a cationic emulsifier and other co-emulsifiers. The physical characteristics of the l...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1007553106681
更新日期：2000-03-01 00:00:00
abstract：PURPOSE:Modulation of 5-HT3 receptor in the central nervous system (CNS) is a promising approach for treatment of neuropathic pain. The goal was to evaluate the role of P-glycoprotein (Pgp) in limiting exposure of different parts of the CNS to ondansetron (5-HT3 receptor antagonist) using wild-type and genetic knockout...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-020-02929-2
更新日期：2020-09-28 00:00:00
abstract：PURPOSE:To characterize the pharmacokinetics of simvastatin (SV) and simvastatin acid (SVA), a lactone-acid pair known to undergo reversible metabolism, and to better understand mechanisms underlying pharmacokinetic interactions observed between SV and gemfibrozil. METHODS:Pharmacokinetic studies were conducted after ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-6037-2
更新日期：2005-07-01 00:00:00
abstract：PURPOSE:A pattern fitting procedure using X-ray powder diffraction patterns was applied to study the crystallization kinetics of amorphous griseofulvin. From the optimized parameters obtained by pattern fitting, a change in the quantity and quality of griseofulvin crystals with crystallization was also investigated. M...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9204-1
更新日期：2007-05-01 00:00:00
abstract：:The possible mechanism of hepatic uptake of colchicine (CLC), a microtubule system disrupting agent, was examined using isolated rat hepatocytes. The existence of a carrier-mediated active transport system for CLC was demonstrated. This transport system is saturable, is affected by metabolic inhibitors (dinitrophenol,...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015917601349
更新日期：1989-03-01 00:00:00
abstract：:Diltiazem (DTZ) is a calcium channel blocker widely used in the treatment of angina and hypertension. DTZ undergoes extensive metabolism yielding several metabolites, some of which are active like N-desmethyldiltiazem (MA), desacetyldiltiazem (M1) and N-desmethyl,desacetyldiltiazem (M2). Due to the nature of its biotr...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016226601988
更新日期：1995-04-01 00:00:00
abstract：PURPOSE:Drug transfer into milk is a general concern during lactation. Because data are limited in human subjects, particularly for new drugs, experimental animal models of lactational drug transfer are critical. This study analyzed drug transfer into milk in a mouse model, as well as the contribution of similar and di...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1085-5
更新日期：2013-09-01 00:00:00
abstract：PURPOSE:We have already demonstrated that the HMG-CoA reductase inhibitor, pravastatin is actively taken up by isolated rat hepatocytes via a multispecific anion transporter (Yamazaki et al., Am. J. Physiol. 264, G36-44, (1993)). We further attempted the quantitative evaluation of this uptake in different experimental ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016226024587
更新日期：1995-11-01 00:00:00
abstract：PURPOSE:To determine the effect of Sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC) on the permeation of cromolyn across Caco-2 cell monolayers and explore the molecular basis for the enhanced absorption. METHODS:Transport studies of cromolyn across Caco-2 cell monolayers were conducted in the presence of various ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-004-7671-9
更新日期：2004-12-01 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：: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：:Micelle-associated epoetin is still a possible explanation for the upsurge of pure red blood cell aplasia associated with subcutaneous use of epoetin alpha in patients with chronic renal failure. ...
journal_title：Pharmaceutical research
pub_type： 评论,信件
doi：10.1007/s11095-006-9573-5
更新日期：2006-03-01 00:00:00
abstract：PURPOSE:We have evaluated a new process, involving solution-enhanced dispersion by supercritical fluids (SEDS), for the production of polymeric microparticles. METHODS:The biodegradable polymers, Poly (DL-lactide-co-glycolide): copolymer composition 50:50 (DL-PLG), Poly (L-lactide) (L-PLA), Poly (DL-lactide) (DL-PLA) ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018868423309
更新日期：1999-05-01 00:00:00
abstract：PURPOSE:To measure the diffusion of nanometer polymersomes through tissue engineered human oral mucosa. METHODS:In vitro models of full thickness tissue engineered oral mucosa (TEOM) were used to assess the penetration properties of two chemically different polymersomes comprising two of block copolymers, PMPC-PDPA an...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-9882-6
更新日期：2009-07-01 00:00:00
abstract：PURPOSE:Gastroduodenal and intestinal permeability were compared after single doses of sustained release and regular release flurbiprofen in the rat to assess possible site-specific formulation-dependent toxicity. METHODS:Pharmacokinetics was assessed and gastrointestinal permeability was evaluated using sucrose and 5...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012134503107
更新日期：1997-11-01 00:00:00
abstract：PURPOSE:Novel itraconazole (ITZ)-based dry powders for inhalation (DPI) were optimized for aerodynamic and dissolution properties and contained excipients that are acceptable for inhalation. METHODS:The DPI were produced by spray drying solutions. The drug content, crystallinity state, and morphological evaluation of ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0779-4
更新日期：2012-10-01 00:00:00
abstract：:To evaluate the effects of a neutron activation radiolabeling technique on an enteric-coated multiparticulate formulation of erythromycin, test quantities were produced under industrial pilot scale conditions. The pellets contained the stable isotope erbium oxide (Er-170), which was later converted by neutron activati...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015826229323
更新日期：1990-03-01 00:00:00
abstract：PURPOSE:The purpose of this study was to determine the existence of insulin-degrading enzyme (EC 3.4.22.11) (IDE) in rat intestinal enterocytes. METHODS:Subcellular fractionation, biochemical characterization, immunoprecipitation, and western blots were employed. RESULTS:Insulin-degrading activity was localized in th...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016263926946
更新日期：1995-08-01 00:00:00
abstract：PURPOSE:This study aims to conduct an impact investigation in the hydrophobic-hydrophilic balance as an important factor for dissolution improvement of a hydrophilic carrier-based solid dispersion system. METHODS:Polymeric carriers with different hydrophobic to hydrophilic ratios were used to prepare several electrosp...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-019-2734-0
更新日期：2020-01-07 00:00:00
abstract：PURPOSE:To measure aggregate and particle formation in tumor necrosis factor-alpha (TNF-α) inhibitors etanercept, adalimumab and certolizumab pegol product samples after exposure to freezing temperature conditions similar to storage conditions previously observed in patients' homes. METHODS:TNF-α inhibitors in their o...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-017-2341-x
更新日期：2018-02-05 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:Comparison of the dissociation kinetics of rapid-acting insulins lispro, aspart, glulisine and human insulin under physiologically relevant conditions. METHODS:Dissociation kinetics after dilution were monitored directly in terms of the average molecular mass using combined static and dynamic light scattering....
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-017-2233-0
更新日期：2017-11-01 00:00:00
abstract：PURPOSE:To evaluate the effect of re-directing the uptake mechanism of polyplexes containing oligodeoxynucleotide (ODN) decoys to nuclear factor kappa B (NF-kappaB) from absorptive-mediated to receptor-mediated endocytosis. MATERIALS AND METHODS:Complexes of ODNs and a co-polymer of biotin-polyethylenglycol and polyet...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9389-y
更新日期：2008-03-01 00:00:00
abstract：:The glass transition temperature of an amorphous pharmaceutical solid is a critical physical property which can dramatically influence its chemical stability, physical stability, and viscoelastic properties. Water frequently acts as a potent plasticizer for such materials, and since many amorphous solids spontaneously...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018941810744
更新日期：1994-04-01 00:00:00
abstract：PURPOSE:This prospective study aimed to evaluate the effects of genetic polymorphisms in sulindac-related metabolizing enzyme genes including FMO3 and AOX1 on the population pharmacokinetics of sulindac in 58 pregnant women with preterm labor. METHODS:Plasma samples were collected at 1.5, 4, and 10 h after first oral ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-020-2765-6
更新日期：2020-01-28 00:00:00
abstract：PURPOSE:We have shown that the three human prostate xenograft tumors, i.e. the androgen-dependent CWR22 tumor, and the androgen-resistant CWR22R and CWR91 tumors, are comparable to patient tumors in their expression of prostate specific antigen, multidrug resistance p-glycoprotein, p53 and Bcl-2 and in their sensitivit...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011921031564
更新日期：1998-11-01 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:The rapid oxidation of rofecoxib under alkaline conditions has been previously reported. The oxidation was reported to involve gamma-lactone ring opening to an alcohol, which further oxidized to a dicarboxyclic acid. The oxidation was suspected to be mediated by peroxy radicals. This work further investigates t...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-6947-z
更新日期：2005-10-01 00:00:00
