Abstract：
:The purpose of the present study was to investigate the effect of seed particles on the precipitation behavior of weak base drugs in the small intestine. A simple in vitro infusion method was used to mimic in vivo processes. Dipyridamole, pioglitazone, topiroxostat, chlorpromazine, cinnarizine, and ketoconazole were used as model drugs. A drug was dissolved in 0.01 N HCl and infused into a pH 6.5 buffer. The existence of seed particles significantly affected the concentration-time profiles of the model drugs in the buffer. The maximum concentration was significantly reduced in the presence of seed particles (except for cinnarizine). In the case of dipyridamole, pioglitazone, and topiroxostat, the precipitants were crystalline from the beginning of precipitation. In contrast, the precipitants of ketoconazole, cinnarizine, and chlorpromazine were a mixture of amorphous and crystals. In conclusion, the presence of seed particles significantly affected the precipitation behavior of weak base drugs.
journal_name
Mol Pharmjournal_title
Molecular pharmaceuticsauthors
Koyama H,Ito M,Terada K,Sugano Kdoi
10.1021/acs.molpharmaceut.6b00297subject
Has Abstractpub_date
2016-08-01 00:00:00pages
2711-7issue
8eissn
1543-8384issn
1543-8392journal_volume
13pub_type
杂志文章abstract：:Bisphosphonates (BPs) are a class of bone resorptive drug with a high affinity for the hydroxyapatite structure of bone matrices that are used for the treatment of osteoporosis. However, clinical application is limited by a common toxicity, BP-related osteonecrosis of the jaw. There is emerging evidence that BPs posse...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.5b00670
更新日期：2016-04-04 00:00:00
abstract：:Aerosol glucocorticoid medications have become more and more important in treating BA (bronchial asthma). Although these agents are dosed to directly target airway inflammation, adrenocortical suppression and other systematic effects are still seen. To tackle this problem in a novel way, two L-carnitine ester derivati...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp100412z
更新日期：2011-10-03 00:00:00
abstract：:In the current study, nanoparticles containing the antimetabolite drug methotrexate (MTX) and the novel tubulin-binding drug pretubulysin (PT) were developed for combination chemotherapy. Polyelectrolyte complexes were formed based on ∼20 nm cationic nanomicelles of lipo-oligomer 454 with the anionic MTX at the molar ...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.9b00038
更新日期：2019-06-03 00:00:00
abstract：:Photostability conditions as prescribed by ICH guidelines induced highly reduction-resistant scrambled disulfides that contribute to the population of apparent nonreducible aggregates in an IgG1 mAb. Photoinduced cross-linked species were isolated under reducing conditions using an organic phase size exclusion chromat...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.7b01128
更新日期：2018-04-02 00:00:00
abstract：:Heparin is a highly sulfated polysaccharide that serves biologically relevant roles as an anticoagulant and anticancer agent. While it is well-known that modification of heparin's sulfation pattern can drastically influence its ability to bind growth factors and other extracellular molecules, very little is known abou...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp300679a
更新日期：2013-04-01 00:00:00
abstract：:New bifunctional hexa- and octadentate analogues of the hydroxamate-containing siderophore desferrichrome (DFC) have been synthesized and evaluated as 89Zr-chelating agents for immunoPET applications. The in vitro and in vivo inertness of these new ligands, Orn3-hx (hexadentate) and Orn-4hx derivatives (octadentate), ...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.7b00343
更新日期：2017-08-07 00:00:00
abstract：:It is well established that polymers adopt a range of conformations and solution-state organization in response to varying solution environments, although very little work has been done to understand how these effects might impact the physical stability and bioavailability of spray-dried amorphous dispersions (SDDs). ...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.0c00729
更新日期：2020-12-07 00:00:00
abstract：:Due to overexpression of glycyrrhetinic acid (GA) receptor in liver cancer cells, glycyrrhetinic acid modified recombinant human serum albumin (rHSA) nanoparticles for targeting liver tumor cells may result in increased therapeutic efficacy and decreased adverse effects of cancer therapy. In this study, doxorubicin (D...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp500394v
更新日期：2015-03-02 00:00:00
abstract：:Pancreatic ductal adenocarcinoma (PDAC) is highly chemo-resistant and has an extremely poor patient prognosis, with a survival rate at five years of <8%. There remains an urgent need for innovative treatments. Targeting polyamine biosynthesis through inhibition of ornithine decarboxylase with difluoromethylornithine (...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.7b00718
更新日期：2018-02-05 00:00:00
abstract：:Block copolymer micelles (BCMs) have been employed as effective drug delivery systems to solid tumors by virtue of their capacity to transport large therapeutic payloads and passively target tumor sites. Active targeting of nanoparticles (NPs) has been exploited as a means to increase the therapeutic efficacy of NP-ba...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp400315p
更新日期：2013-11-04 00:00:00
abstract：:Cold crystallization of amorphous pharmaceuticals is an important aspect in the search to stabilize amorphous or glassy compounds used as amorphous pharmaceutical ingredients (APIs). In the present work, we report results for the isothermal crystallization of the compound GDC-0276 based on differential scanning calori...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.0c00776
更新日期：2021-01-04 00:00:00
abstract：:Carbonic anhydrase IX (CAIX) plays an important role in glioma cell proliferation, invasion, metastasis, and resistance to radiotherapy and chemotherapy. An effective and noninvasive PET molecular imaging agent targeting CAIX would help its diagnosis and treatment but is not currently available. Recently, a low-molecu...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.8b01210
更新日期：2019-04-01 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：:Noninvasive measurement of human islet cell mass in pancreas or following islet transplantation by nuclear imaging has yet to be achieved. It has been shown using mouse tumor models that pretargeting imaging strategies are sensitive and can greatly increase target to nontarget signal ratios. The objective now is to de...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp100382m
更新日期：2011-06-06 00:00:00
abstract：:Low molecular weight nucleoside gelators hold great promise in drug delivery and particularly for the delivery of biologics because of their excellent biocompatibility. However, the influence of these gelators on protein aggregation inhibition has not yet been studied. Protein aggregation is the most significant cause...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.8b01013
更新日期：2019-01-07 00:00:00
abstract：:To predict the outcome of intestinal drug transporter induction on pharmacokinetics, signaling of the DNA message along with messenger RNA (mRNA) transcription and protein translation leading to transporter function must be understood. We quantified the gene expression of PXR and CAR, gene expression and protein abund...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.9b00458
更新日期：2019-09-03 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：:Extracellular β-glucuronidase (β-GUS) in tumors has been investigated as a target enzyme for prodrug therapy. However, despite encouraging preclinical results, animal studies also indicate that the success of prodrug therapy might be limited by the insufficient prodrug-converting enzyme activity, especially in small t...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp300327w
更新日期：2012-11-05 00:00:00
abstract：:Adsorption of antibody therapeutics to air-liquid interfaces can enhance aggregation, particularly when the solution does not contain protective surfactant or when the surfactant is diluted as occurs during preparation of intravenous infusion bags. The ability to predict an antibody's propensity for interfacially medi...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.5b00089
更新日期：2015-09-08 00:00:00
abstract：:Photodynamic therapy, a procedure that uses a photosensitizer to enable light therapy selectively at diseased sites, remains underutilized in oncological clinic. To further improve its cancer selectivity, we developed a polymeric nanosystem by conjugating a photosensitizer IRDye 700DX (IR700) and cancer targeting RGD ...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.8b00088
更新日期：2018-07-02 00:00:00
abstract：:An effective short interfering RNA (siRNA) delivery system protects the siRNA from degradation, facilitates its cellular uptake, and promotes its release into the cytoplasm. Local administration of siRNA presents advantages over systemic administration, such as the possibility to use lower doses and allow local and su...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.6b01141
更新日期：2017-05-01 00:00:00
abstract：:Supersaturable active pharmaceutical ingredients (sAPI), such as salts, cocrystals, and amorphous solids, can form supersaturated solutions after dissolving in the gastrointestinal fluids. However, there are cases in which supersaturation is not observed in an in vitro nonsink dissolution test. The purpose of the pres...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.9b00006
更新日期：2019-04-01 00:00:00
abstract：:Although nitric oxide (NO) is a bactericidal component of the macrophage's innate response to intracellular infections such as tuberculosis (TB), prolonged inhalation of NO gas has little benefit in chemotherapy of TB. The impact of controlled release of NO through intracellular delivery of NO donors to macrophages in...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp300269g
更新日期：2012-11-05 00:00:00
abstract：:Ratiometric fluorescence and cellular fractionation studies were employed to characterize the intracellular trafficking dynamics of antibody-poly(propylacrylic acid) (PPAA) conjugates in CD22+ RAMOS-AW cells. The HD39 monoclonal antibody (mAb) directs CD22-dependent, receptor-mediated uptake in human B-cell lymphoma c...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp300338s
更新日期：2012-12-03 00:00:00
abstract：:This work demonstrates the way to achieve efficient and target specific delivery of a graphene quantum dot (GQD) using hyaluronic acid (HA) (GQD-HA) as a targeting agent. HA has been anchored to a GQD that accepts the fascinating adhesive properties of the catechol moiety, dopamine hydrochloride, conjugated to HA, whi...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp400219u
更新日期：2013-10-07 00:00:00
abstract：:Recently we characterized an unusual switch in the internalization mechanism of the monomeric and dimeric forms of the cell-penetrating peptide RDLWEMMMVSLACQY. Here, we observed both energy-dependent and energy-independent modes of peptide uptake by the target B-lymphocytes WI-L2-729HF2, suggesting that higher-order ...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp050035b
更新日期：2005-11-01 00:00:00
abstract：:Multidrug resistance (MDR), a major obstacle to successful cancer chemotherapy, may be induced by amplification of the MDR1 gene and overexpression of the P-glycoprotein (P-gp), which acts as drug efflux pump decreasing intracellular drug accumulation. In this study, an antisense oligodeoxynucleotide--doxorubicin conj...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp800001j
更新日期：2008-07-01 00:00:00
abstract：:Cancer is a leading cause of death within developed nations, and part of this morbidity is due to difficulties associated with its treatment. Currently, anticancer therapy relies heavily upon the administration of small molecule cytotoxic drugs that attack both cancerous and noncancerous cells due to limited selectivi...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章,评审
doi：10.1021/mp2005966
更新日期：2012-03-05 00:00:00
abstract：:Isoniazid (INH) is still one of the two most effective antitubercular drugs and is included in all recommended multitherapeutic regimens. Because of the increasing resistance of Mycobacterium tuberculosis to INH, mainly associated with mutations in the katG gene, new INH-based compounds have been proposed to circumven...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp500736n
更新日期：2015-03-02 00:00:00
abstract：:The pharmacological exploitation of resveratrol is hindered by rapid phase-II conjugative metabolism in enterocytes and hepatocytes. One approach to the solution of this problem relies on prodrugs. We report the synthesis and characterization as well as the assessment of in vivo absorption and metabolism of a set of p...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp400226p
更新日期：2013-07-01 00:00:00
