Abstract:
:Ipratropium bromide, an anticholinergic drug used for the treatment of asthma and chronic obstructive pulmonary disease, has low oral bioavailability, but systemic exposure, superior to oral administration, can be achieved by inhalation. Therefore, we investigated the pulmonary absorption mechanism of ipratropium using human bronchial epithelial BEAS-2B cells. [3H]Ipratropium uptake by BEAS-2B cells was temperature-dependent and saturable, with a K(m) value of 78.0 microM, suggesting involvement of carrier-mediated uptake. An RT-PCR study showed that organic cation/carnitine transporters OCTN1 and OCTN2 are expressed in BEAS-2B cells, but organic cation transporters (OCTs) are not. Uptake of [3H]ipratropium by HEK293 cells expressing OCTN1 (HEK293/OCTN1) and OCTN2 (HEK293/OCTN2) was significantly increased, compared with mock-transfected cells, and the estimated K(m) values were 444 microM and 53.0 microM, respectively. Finally, the contributions of OCTN1 and OCTN2 to ipratropium uptake were evaluated by measuring [3H]ipratropium uptake by BEAS-2B cells in which OCTN1 or OCTN2 gene expression had been silenced. Knock-down of OCTN1 or OCTN2 suppressed the uptake of [3H]ipratropium to 78.2% and 14.8% of that by control BEAS-2B cells, respectively. In addition, another anticholinergic, tiotropium, was also taken up by both HEK293/OCTN1 and HEK293/OCTN2 cells. Therefore, ipratropium and tiotropium are taken up primarily by OCTN2, and to a lesser extent by OCTN1, in bronchial epithelial cells. These findings are consistent with the pharmacological activity of the drugs after administration via inhalation.
journal_name
Mol Pharmjournal_title
Molecular pharmaceuticsauthors
Nakamura T,Nakanishi T,Haruta T,Shirasaka Y,Keogh JP,Tamai Idoi
10.1021/mp900206jsubject
Has Abstractpub_date
2010-02-01 00:00:00pages
187-95issue
1eissn
1543-8384issn
1543-8392journal_volume
7pub_type
杂志文章abstract::Therapeutic monoclonal antibodies are currently delivered mainly via the intravenous route, since large volumes are often required to deliver a therapeutic dose. Administration via the subcutaneous route would have several therapeutic advantages; the absorption mechanisms for antibodies dosed subcutaneously are poorly...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp400464s
更新日期:2014-02-03 00:00:00
abstract::Photodynamic therapy (PDT) has been shown to kill cancer cells and improve survival and quality of life in cancer patients, and numerous new approaches have been considered for maximizing the efficacy of PDT. In this study, a new multifunctional nanophotosensitizer Ce6/GE11-(pH)micelle was developed to target epiderma...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00925
更新日期:2018-04-02 00:00:00
abstract::The controlled release of anticancer drugs at the tumor site is a central challenge in treating cancer. To achieve this goal, our strategy was based on tumor-specific targeting and ultrasound-triggered release of an anticancer agent from liposomal nanocarriers. To enhance the ultrasound-triggered drug release, we inco...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b00194
更新日期:2019-07-01 00:00:00
abstract::The small molecule fluorescein is commonly used to guide the repair of cerebral spinal fluid leaks (CSFLs) in the clinic. We modified fluorescein so that it is also visible by positron emission tomography (PET). This probe was used to quantitatively track the fast distribution of small molecules in the CSF of rats. We...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b00485
更新日期:2019-08-05 00:00:00
abstract::Bioadhesive nanoparticles based on poly(vinyl methyl ether/maleic anhydride) (PVMMA) and poly(ethylene glycol) methyl ether-b-poly(d,l-lactic acid) (mPEG-b-PLA) were produced by the emulsification solvent evaporation method. Paclitaxel was utilized as the model drug, with an encapsulation efficiency of up to 90.2 ± 4....
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00612
更新日期:2017-10-02 00:00:00
abstract::Cyclic RGD (cRGD) peptide-conjugated boronated albumin was developed to direct toward integrin αvβ3, which overexpresses on many cancer cells. A stepwise conjugation of c[RGDfK(Mal)] and maleimide-conjugated closo-dodecaborate (MID) to bovine serum albumin (BSA) afforded cRGD-MID-BSA, which was noncytotoxic toward bot...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.0c00478
更新日期:2020-10-05 00:00:00
abstract::Herein, we elucidated the mechanisms and key factors for the tumor-targeting ability of nanoparticles that presented high targeting efficiency for liver tumor. We used several different nanoparticles with sizes of 200-300 nm, including liposome nanoparticles (LNPs), polystyrene nanoparticles (PNPs) and glycol chitosan...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.6b00507
更新日期:2016-11-07 00:00:00
abstract::Intravitreal sustained delivery of corticosteroids such as dexamethasone is an effective means of treating a number of ocular diseases, including diabetic retinopathy, uveitis, and age-related or diabetic macular edema. There are currently marketed devices for this purpose, yet only one, Ozurdex, is degradable. In vit...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.6b00358
更新日期:2016-09-06 00:00:00
abstract::Much interest has been expressed in this work on the role of water diffusivity in the release media as a new parameter for predicting drug release. NMR was used to measure water diffusivity in different media varying in their osmolality and viscosity. Water self-diffusion coefficients in sucrose, sodium chloride, and ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp3006209
更新日期:2013-06-03 00:00:00
abstract::By the combined use of powder and single-crystal X-ray diffraction, solid-state NMR, and molecular modeling, the crystal structures of two systems containing the unusually large tenapanor drug molecule have been determined: the free form, ANHY, and a dihydrochloride salt form, 2HCl. Dynamic nuclear polarization (DNP) ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b01047
更新日期:2018-04-02 00:00:00
abstract::The αvβ3-integrin addressing cyclic pentapeptide cyclo(RGDfK) was conjugated to NOPO, 1,4,7-triazacyclononane-1,4-bis[methylene(hydroxymethyl)phosphinic acid]-7-[methylene(2-carboxyethyl)phosphinic acid], a bifunctional chelator with exceptional gallium-68 labeling properties. NOPO-c(RGDfK) and its Ga(III) and Cu(II) ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp5000746
更新日期:2014-05-05 00:00:00
abstract::Compared with peripheral tumors, glioma is very difficult to treat, not only because it has general features of tumor but also because the therapy has been restricted by the brain-blood barrier (BBB). The two main features of tumor growth are angiogenesis and proliferation of tumor cells. RNA interference (RNAi) can d...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.6b00051
更新日期:2016-05-02 00:00:00
abstract::The adenosine triphosphate-binding cassette transporter P-glycoprotein (ABCB1/Abcb1a) restricts at the blood-brain barrier (BBB) brain distribution of many drugs. ABCB1 may be involved in drug-drug interactions (DDIs) at the BBB, which may lead to changes in brain distribution and central nervous system side effects o...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.5b00168
更新日期:2015-09-08 00:00:00
abstract::Our previous studies have demonstrated that a generation 5 dendrimer (G5) conjugated with both folic acid (FA) and methotrexate (MTX) has a higher chemotherapeutic index than MTX alone. Despite this, batch-to-batch inconsistencies in the number of FA and MTX molecules linked to each dendrimer led to conjugate batches ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp3002232
更新日期:2012-09-04 00:00:00
abstract::In this work, we demonstrated that the simple substitution of the 1,2,4-triazole moiety in 5-( 4H-1,2,4-triazol-4-yl)isophthalic acid (5-TIA) by the 1 H-1,2,3-triazol-5-yl unit enables the preparation of a hydrogelator (click-TIA). In sharp contrast to 5-TIA, its isostere click-TIA undergoes self-assembly in water upo...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b01049
更新日期:2018-08-06 00:00:00
abstract::Gemcitabine (GEM), a first-line chemotherapy for pancreatic cancer undergoes rapid metabolism and develops chemoresistance after repeated administration. We previously demonstrated that the combination of GEM and miR-205 provides an effective therapeutic strategy to sensitize GEM-resistant pancreatic cancer cells. Sin...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00355
更新日期:2017-09-05 00:00:00
abstract::Protein drugs play an important role in modern day medicine. Typically, these proteins are formulated as liquids requiring cold chain processing. To circumvent the cold chain and achieve better storage stability, these proteins can be dried in the presence of carbohydrates. We demonstrate that thermal gradient mid- an...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00568
更新日期:2017-10-02 00:00:00
abstract::The effect of tertiary butyl alcohol (TBA) as a cosolvent on the phase behavior of mannitol in frozen and freeze-dried systems was characterized using differential scanning calorimetry (DSC) and X-ray diffractometry (XRD; laboratory and synchrotron sources). Solutions of mannitol (2 and 5% w/w) in TBA-water systems of...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.0c00492
更新日期:2020-08-03 00:00:00
abstract::DEK protein is critical to the formation of neutrophil extracellular traps (NETs) in rheumatoid arthritis (RA). Blocking DEK using the aptamer DTA via articular injection has been shown to have robust anti-inflammatory efficacy in a previous study. However, DTA is prone to nuclease degradation and renal clearance in v...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.0c00954
更新日期:2021-01-04 00:00:00
abstract::Ultrasound-targeted microbubble destruction (UTMD) is a promising technique to facilitate the delivery of chemotherapy in cancer treatment. However, the process typically uses nonspecific microbubbles, leading to low tumor-to-normal tissue uptake ratio and adverse side effects. In this study, we synthesized the LHRH r...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp400523h
更新日期:2014-01-06 00:00:00
abstract::Nucleic acid biopharmaceuticals are being investigated as potential therapeutics. They need to be incorporated into a biocompatible carrier so as to overcome several biological barriers. Rational development of suitable nanocarriers requires high-quality characterization techniques. While size, concentration, and stab...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00999
更新日期:2018-03-05 00:00:00
abstract::The ability to select patients who will respond to therapy is especially acute for autoimmune/inflammatory diseases, where the costs of therapies can be high and the progressive damage associated with ineffective treatments can be irreversible. In this article we describe a clinical test that will rapidly predict the ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.5b00134
更新日期:2015-10-05 00:00:00
abstract::Simvastatin is known to exist in at least three polymorphic forms. The nature of polymorphism in simvastatin is ambiguous, as the crystal structures of the polymorphs do not show any significant change in crystal packing or molecular conformation. We utilize terahertz time-domain spectroscopy to characterize each of t...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp500649q
更新日期:2015-03-02 00:00:00
abstract::Paracetamol has been one of the most commonly used and prescribed analgesic drugs for more than a hundred years. Despite being generally well tolerated, it can result in high liver toxicity when administered in specific conditions, such as overdose, or in vulnerable individuals. We have synthesized and characterized a...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b00508
更新日期:2019-10-07 00:00:00
abstract::Following oral administration, dabigatran etexilate (DABE) is rapidly hydrolyzed to its active form, dabigatran. DABE, but not dabigatran, presents as a P-glycoprotein (P-gp) substrate and has increasingly been used as a probe drug. Therefore, although dosed as DABE, a P-gp drug-drug interaction (DDI) is reported as a...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b00472
更新日期:2019-09-03 00:00:00
abstract::Preferential interactions of formulation excipients govern their overall interactions with protein molecules, and molecular dynamics simulations allow for the examination of the interactions at the molecular level. We used molecular dynamics simulations to examine the interactions of sorbitol, sucrose, and trehalose w...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b00545
更新日期:2019-08-05 00:00:00
abstract::A general, easy-to-implement strategy for mapping the structure of organic phases integrated in mesoporous silica drug delivery devices is presented. The approach based on a few straightforward solid-state NMR techniques has no limitations regarding concentrations of the active compounds and enables straightforward di...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00167
更新日期:2017-06-05 00:00:00
abstract::The particular characteristics of the tumor microenvironment have the potential to strongly promote tumor growth, metastasis and angiogenesis and induce drug resistance. Therefore, the development of effective, systemic therapeutic approaches specifically based on the tumor microenvironment is highly desirable. Hypoxi...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp300193f
更新日期:2012-10-01 00:00:00
abstract::Liposomes are representative lipid nanoparticles widely used for delivering anticancer drugs, DNA fragments, or siRNA to cancer cells. Upon targeting, various internal and external triggers have been used to increase the rate for contents release from the liposomes. Among the internal triggers, decreased pH within the...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp500186a
更新日期:2014-11-03 00:00:00
abstract::Cell penetrating peptides (CPPs) have been extensively studied in polyelectrolyte complexes as a means to enhance the transfection efficiency of plasmid DNA (pDNA). Increasing the molecular weight of CPPs often enhances gene expression but poses a risk of increased cytotoxicity and immunogenicity compared to low molec...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp3007117
更新日期:2013-05-06 00:00:00