Abstract:
PURPOSE:To study the use of poly (lactide-co-glycolide) (PLGA) microparticles in respirable sizes as carriers for recombinant tuberculosis (TB) antigen, TB10.4-Ag85B, with the ultimate goal of pulmonary delivery as vaccine for the prevention of TB. MATERIALS AND METHODS:Recombinant TB antigens were purified from E. coli by FPLC and encapsulated into PLGA microparticles by emulsion/spray-drying. Spray-drying condition was optimized by half-factorial design. Microparticles encapsulating TB antigens were assessed for their ability to deliver antigens to macrophages for subsequent presentation by employing an in vitro antigen presentation assay specific to an Ag85B epitope. RESULTS:Spray-drying condition was optimized to prepare PLGA microparticles suitable for pulmonary delivery (aerodynamic diameter of 3.3 microm). Antigen release from particles exhibited an initial burst release followed by sustained release up to 10 days. Antigens encapsulated into PLGA microparticles induced much stronger interleukin-2 secretion in a T-lymphocyte assay compared to antigen solutions for three particle formulations. Macrophages pulsed with PLGA-MDP-TB10.4-Ag85B demonstrated extended epitope presentation. CONCLUSION:PLGA microparticles in respirable sizes were effective in delivering recombinant TB10.4-Ag85B in an immunologically relevant manner to macrophages. These results set the foundation for further investigation into the potential use of PLGA particles for pulmonary delivery of vaccines to prevent Mycobacterium tuberculosis infection.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Shi S,Hickey AJdoi
10.1007/s11095-009-0028-7subject
Has Abstractpub_date
2010-02-01 00:00:00pages
350-60issue
2eissn
0724-8741issn
1573-904Xjournal_volume
27pub_type
杂志文章abstract:PURPOSE:To synthesize a trifluorinated bile acid that can be used for (19)F magnetic resonance imaging (MRI) of bile acid enterohepatic circulation, characterize its in vitro transporter affinity, stability, and (19)F-MRI signal, and assess its ability to concentrate in the gallbladder of C57BL/6 mice. METHODS:Target ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0963-6
更新日期:2013-05-01 00:00:00
abstract::The efficacy of topical formulations of acidic fibroblast growth factor (aFGF) in healing of full-thickness wounds has been studied in a diabetic db+/db+ mouse model. The effect of several formulation variables, dose, and application frequency was examined. It was found that wound healing in diabetic animals treated w...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018993610801
更新日期:1994-01-01 00:00:00
abstract::A liposomal formulation of methylprednisolone (L-MPL) was developed to improve localization of this immunosuppressant in lymphatic tissues. Liposomes containing MPL were formulated from a mixture of phosphatydylcholine and phosphatydylglycerol (molar ratio, 9:1) and sized by extrusion through a 0.1-micron membrane. Ma...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018954704886
更新日期:1993-10-01 00:00:00
abstract:PURPOSE:Recombinant human serum albumin (rHSA), secreted by a Pichia pastoris expression system, was purified by a fast and efficient method, the essential feature of which is strong but reversible binding of the protein to Blue Sepharose. The structural characteristics, stability, and ligand-binding properties of the ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1013391001141
更新日期:2001-12-01 00:00:00
abstract:PURPOSE:Excipients are added to lyophilized protein drug formulations to protect the protein during processing and storage, but the mechanisms are poorly understood. Here, hydrogen/deuterium (H/D) exchange with mass spectrometry was used to assess protein conformation and excipient interactions in lyophilized solids. ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9365-6
更新日期:2008-02-01 00:00:00
abstract:PURPOSE:Solid dispersions (SDs) represent the most common formulation technique used to increase the dissolution rate of a drug. In this work, the three most common methods used to prepare SDs, namely spray-drying, solvent-casting and freeze-drying, have been compared in order to investigate their effect on increasing ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-020-2778-1
更新日期:2020-02-19 00:00:00
abstract:PURPOSE:Delivery of apoptosis-inducing compounds to hepatic stellate cells (HSC) may be an effective strategy to reverse liver fibrosis. The aim of this study was therefore to examine the selective targeting of the apoptosis-inducing drug 15-deoxy-delta12,14-prostaglandin J2 (15dPGJ2) with two different HSC-carriers: h...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-006-9175-2
更新日期:2007-03-01 00:00:00
abstract::Semitelechelic poly[N-(2-hydroxypropyl)methacrylamide]s (ST-PHPMA) containing one amino end-group and differing in molecular weight were synthesized by radical polymerization in the presence of 2-aminoethanethiol (AET) as chain transfer agent. These polymers were covalently attached via amide bonds to the surface of n...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016247206531
更新日期:1995-05-01 00:00:00
abstract::A novel floating controlled-release drug delivery system was formulated in an effort increase the gastric retention time of the dosage form and to control drug release. The buoyancy was attributed to air and oil entrapped in the agar gel network. A floating controlled-release 300-mg theophylline tablet having a densit...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018921830385
更新日期:1993-09-01 00:00:00
abstract:PURPOSE:The blood-brain barrier (BBB) essentially restricts therapeutic drugs from entering into the brain. This study tests the hypothesis that brain endothelial cell derived exosomes can deliver anticancer drug across the BBB for the treatment of brain cancer in a zebrafish (Danio rerio) model. MATERIALS AND METHODS...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-014-1593-y
更新日期:2015-06-01 00:00:00
abstract::The area function method for assessing zero-order (ko) drug absorption rates was compared to four other methods under conditions where variation occurs in the plasma concentration data and in the elimination rate constant (kel or k10) for one- or two-compartment models. For deviant kel values of a one-compartment mode...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015843811150
更新日期:1990-01-01 00:00:00
abstract:PURPOSE:To quantitatively compare in vitro dissolution data in biorelevant and compendial media, to investigate whether in vitro differences are reflected in the simulated plasma profile and to specify under which circumstances prediction of the plasma profile of orally administered lipophilic drugs can be achieved. M...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011071401306
更新日期:2001-03-01 00:00:00
abstract:PURPOSE:To examine whether the glass transition temperature (Tg) of freeze-dried formulations containing polymer excipients can be accurately predicted by molecular dynamics simulation using software currently available on the market. Molecular dynamics simulations were carried out for isomaltodecaose, a fragment of de...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1023831102203
更新日期:2003-06-01 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:Reverse iontophoresis is an alternative to blood sampling for the monitoring of endogenous molecules. Here, the potential of the technique to measure urea and potassium levels non-invasively, and to track their concentrations during hemodialysis, has been examined. MATERIALS AND METHODS:In vitro experiments we...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9237-0
更新日期:2007-06-01 00:00:00
abstract::To achieve time-controlled or site-specific drug delivery in the gastrointestinal tract, a sigmoidal release system (SRS) was developed, which achieved a prolonged lag time, followed by rapid release. The theophylline beads with a thick Eudragit RS film coating showed very low drug release in water, whereas the releas...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018910114436
更新日期:1994-01-01 00:00:00
abstract:PURPOSE:To evaluate organic anion transporter-mediated drug-drug interaction (DDI) potential for individual active components of Danshen (Salvia miltiorrhiza) vs. combinations using in vitro and in silico approaches. METHODS:Inhibition profiles for single Danshen components and combinations were generated in stably-ex...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-014-1437-9
更新日期:2014-12-01 00:00:00
abstract::Although much effort has been devoted to opioid research since the identification of enkephalins, understanding of the physiological importance and mechanisms of action of endogenous opioids lags behind understanding of opiate alkaloids such as morphine. In recent years, several novel approaches have been refined with...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1023/a:1015809702296
更新日期:1991-01-01 00:00:00
abstract::Nanobiosensors with high sensitivity and specificity have shown great potential in the detection of diseases. The incorporation of therapeutic agents with nanobiosensors allows the simultaneous diagnosis and therapy of diseases. The delivery of nanobiosensors and therapeutic agents using polymers is a common strategy ...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-016-1944-y
更新日期:2016-10-01 00:00:00
abstract:PURPOSE:We reported that suramin produced chemosensitization at nontoxic doses. This benefit was lost at the approximately 10-fold higher, maximally tolerated doses (MTD). The aim of the current study was to identify in patients the chemosensitizing suramin dose that delivers 10-50 microM plasma concentrations over 48 ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-006-0165-1
更新日期:2006-06-01 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 purpose was to develop a population pharmacokinetic model for montelukast after intravenous administration. Clinical trial simulations were conducted using the model developed to identify the lowest intravenous dose in 6- to 14-year-old children that would give montelukast systemic exposures that were compa...
journal_title:Pharmaceutical research
pub_type: 杂志文章,随机对照试验
doi:10.1007/s11095-005-2493-y
更新日期:2005-04-01 00:00:00
abstract:PURPOSE:Penetration enhancers (PEs) enhancing efficacy depends on two processes: PEs release from patches and action on skin. Compared with their action on skin, PEs release process was poorly understood. Therefore, the purpose of this study was to make a mechanistic understanding of PEs release from acrylic pressure-s...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-020-02901-0
更新日期:2020-08-13 00:00:00
abstract:PURPOSE:To improve upon the theory of reasoned action and apply it to pharmaceutical research, we investigated the effects of relevant appraisals attributes, and past behavior of physicians on the use of drug information sources. We also examined the moderating effects of practice characteristics. METHODS:A mail quest...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1012143915886
更新日期:1997-10-01 00:00:00
abstract::Antibody drug conjugates (ADCs) are a class of therapeutics that combine the target specificity of an antibody with the potency of a chemotherapeutic. This therapeutic strategy can significantly expand the therapeutic index of a chemotherapeutic by minimizing the systemic exposure and associated toxicity of the chemot...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-012-0800-y
更新日期:2012-09-01 00:00:00
abstract::5'-Ester derivatives of 5-iodo-2'-deoxyuridine (IDU) with varying degrees of lipophilicity were examined to evaluate the effectiveness of lipophilic ester prodrugs for enhanced and sustained delivery of IDU to the brain parenchyma. Approximately 1.0% (1.0 +/- 0.19; n = 4) of the total radioactivity was found in the br...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015803922401
更新日期:1992-09-01 00:00:00
abstract:PURPOSE:Since the absorption of ceftriaxone (CTO) in the intestine is restricted by its natural physiological characteristics, we developed a series of small synthetic compounds derived from bile acids to promote the absorption of CTO in the gastrointestinal tract. METHODS:Several bile acid derivatives were screened b...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0932-0
更新日期:2013-04-01 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:This work describes a method for functionalisation of nanoparticle surfaces with hydrophilic "nano-shields" and the application of advanced surface characterisation to determine PEG amount and accumulation at the outmost 10 nm surface that is the predominant factor in determining protein and cellular interactio...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-013-1018-3
更新日期:2013-07-01 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