Abstract:
:The caveolin scaffolding domain peptide (CSP) is being developed for the therapeutic intervention of a lethal lung disease, idiopathic pulmonary fibrosis. While direct respiratory delivery of CSP7 (a 7-mer fragment of CSP) is considered an effective route, proper formulation and processing of the peptide are required. First, air-jet milling technology was performed in order to micronize the neat peptide powder. Next, the fine particles were subjected to a stability study with physical and chemical characterizations. In addition, the in vivo efficacy of processed CSP7 powder was evaluated in an animal model of lung fibrosis. The results revealed that, with jet milling, the particle size of CSP7 was reduced to a mass median aerodynamic diameter of 1.58 ± 0.1 μm and 93.3 ± 3.3% fine particle fraction, optimal for deep lung delivery. A statistically significant reduction of collagen was observed in diseased lung tissues of mice that received CSP7 powder for inhalation. The particles remained chemically and physically stable after micronization and during storage. This work demonstrated that jet milling is effective in the manufacturing of a stable, excipient-free CSP7 inhalation powder for the treatment of pulmonary fibrosis.
journal_name
Mol Pharmjournal_title
Molecular pharmaceuticsauthors
Zhang Y,MacKenzie B,Koleng JJ,Maier E,Warnken ZN,Williams RO 3rddoi
10.1021/acs.molpharmaceut.9b01085subject
Has Abstractpub_date
2020-02-03 00:00:00pages
632-644issue
2eissn
1543-8384issn
1543-8392journal_volume
17pub_type
杂志文章abstract::Oleanolic acid (OA) is a well-known pentacyclic triterpenoid compound, which has been used as a dietary supplement and is supplied as an over-the-counter drug for the treatment of human liver diseases. These are reasons for the low bioavailability of OA which have restricted its wider application. In this study, two O...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.6b00129
更新日期:2016-05-02 00:00:00
abstract::The controversy surrounding the use of diphtheria toxin (DT) as a therapeutic agent against tumor cells arises mainly from its unexpected harmfulness to healthy tissues. We encoded the cytotoxic fragment A of DT (DTA) as an objective gene in the Light-On gene-expression system to construct plasmids pGAVPO (pG) and pU5...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b01038
更新日期:2020-01-06 00:00:00
abstract::Oral chemotherapy with SN38 is restricted by its poor solubility in gastrointestinal (GI) fluids and low permeability. Here we report the oral delivery of SN38 by a combined lipophilic prodrug and lipid-based formulation strategy. A lead lipophilic prodrug of SN38, SN38-undecanoate (SN38-unde20), was incorporated into...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.6b00591
更新日期:2016-10-03 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::The objective was to determine the disposition of polymer nanoparticles and an associated, lipophilic, model "active" component on and within the skin following topical application. Polystyrene and poly(methyl methacrylate) nanoparticles containing covalently bound fluorescein methacrylate and dispersed Nile Red were ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp9001188
更新日期:2009-09-01 00:00:00
abstract::PCPP, a well-defined polyphosphazene macromolecule, has been studied as an immunoadjuvant for a soluble form of the postfusion glycoprotein of respiratory syncytial virus (RSV sF), which is an attractive vaccine candidate for inducing RSV-specific immunity in mice and humans. We demonstrate that RSV sF-PCPP formulatio...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00118
更新日期:2017-07-03 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::In this study, transferrin (Tf)-modified poly(ethylene glycol)-phosphatidylethanolamine (mPEG-PE) micelles loaded with the poorly water-soluble drug, R547 (a potent and selective ATP-competitive cyclin-dependent kinase (CDK) inhibitor), were prepared and evaluated for their targeting efficiency and cytotoxicity in vit...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp300633f
更新日期:2014-02-03 00:00:00
abstract::Retinal pigment epithelium, which forms the outer blood-retinal barrier, is a critical barrier for transport of drugs to the retina. The purpose of this study was to develop a pigmented MDCK (P-MDCK) cell line as a rapidly established in vitro model for the outer blood-retinal barrier to assess the influence of melani...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp300305f
更新日期:2012-11-05 00:00:00
abstract::Although tumor-targeting nanovehicles for hepatocellular carcinoma (HCC) chemotherapy have attracted great research and clinic interest, the poor cancer penetration, inefficient cellular uptake, and slow intracellular drug release greatly compromise their therapeutic outcomes. In this work, a multifunctional mixed mic...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00404
更新日期:2017-11-06 00:00:00
abstract::Microspheres of bovine serum albumin (BSA) and silk fibroin are produced by applying ultrasound in a biphasic system consisting of an aqueous protein solution and an organic solvent. The protein microspheres are dispersed in an aqueous media where the protein remains at the interface covering the organic solvent. This...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp3001827
更新日期:2012-11-05 00:00:00
abstract::Invasion and metastasis of cancer directly related to human death have been associated with interactions among many different types of cells and three-dimensional (3D) tissue matrices. Precise mechanisms related to cancer invasion and metastasis still remain unknown due to their complexities. Development of tumor micr...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.5b00953
更新日期:2016-07-05 00:00:00
abstract::Approximately, 40-70% of active pharmaceutical ingredients (API) are severely limited by their extremely poor aqueous solubility, and consequently, there is a high demand for excipients that can be used to formulate clinically relevant doses of these drug candidates. Here, proof-of-concept studies demonstrate the pote...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.5b00723
更新日期:2016-03-07 00:00:00
abstract::The thermal unfolding and subsequent aggregation of the unglycosylated Fc fragment of a human IgG1 antibody (Fc) were studied in the salt solutions of Na(2)SO(4), KF, KCl and KSCN at pH 4.8 and 7.2 below and at its pI of 7.2, respectively, using differential scanning calorimetry (DSC), far ultraviolet circular dichroi...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp300378y
更新日期:2013-02-04 00:00:00
abstract::Interactions of a lyophilized peptide with water and excipients in a solid matrix were explored using photolytic labeling. A model peptide "KLQ" (Ac-QELHKLQ-NHCH3) was covalently labeled with NHS-diazirine (succinimidyl 4,4'-azipentanoate), and the labeled peptide (KLQ-SDA) was formulated and exposed to UV light in bo...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.8b01031
更新日期:2019-03-04 00:00:00
abstract::Metastasis is the primary cause resulting in the high mortality of breast cancer. The inherent antimetastasis bioactivity of Pluronic copolymers with a wide range of hydrophilic-lipophilic balance (HLB) including Pluronic L61, P85, P123, F127, F68, and F108 was first explored on metastatic 4T1 breast cancer cells. The...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.5b00319
更新日期:2015-09-08 00:00:00
abstract::The blood-brain barrier (BBB) prevents most drugs from reaching the site of central nervous system (CNS) diseases, intensively confining the therapeutic efficiency. Angiopep-2 (here termed (L)Angiopep), which is a 19-mer peptide derived from human Kunitz domain, can trigger transcytosis and traverse the BBB by recogni...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp500086e
更新日期:2014-10-06 00:00:00
abstract::We report on tailored lipid-polymer hybrid nanoparticles (NPs) delivering nitric oxide (NO) under the control of visible light as a tool for overcoming doxorubicin (DOX) resistance. The NPs consist of a polymeric core and a coating. They are appropriately designed to entrap DOX in the poly(lactide-co-glycolide) core a...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.0c00290
更新日期:2020-06-01 00:00:00
abstract::This study describes a novel nonlinear variant of the well-known Yalkowsky general solubility equation (GSE). The modified equation can be trained with small molecules, mostly from the Lipinski Rule of 5 (Ro5) chemical space, to predict the intrinsic aqueous solubility, S0, of large molecules (MW > 800 Da) from beyond...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.0c00689
更新日期:2020-10-05 00:00:00
abstract::Understanding protein stability is central to combatting protein aggregation diseases and developing new protein therapeutics. At the high concentrations often present in biological systems, purified proteins can exhibit undesirable high solution viscosities and poor solubilities mediated by short-range electrostatic ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00322
更新日期:2017-10-02 00:00:00
abstract::Abnormal tumor vessels impede the transport and distribution of chemotherapeutics, resulting in low drug concentration at tumor sites and compromised drug efficacy. Normalizing tumor vessels can modulate tumor vascular permeability, alleviate tumor hypoxia, increase blood perfusion, attenuate interstitial fluid pressu...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00475
更新日期:2017-10-02 00:00:00
abstract::HEPES has been widely employed as an organic buffer agent in cell culture medium as well as uptake and transport experiments in vitro. However, concentrations of HEPES used in such studies vary from one laboratory to another. In this study, we investigated the effect of HEPES on the uptake and bidirectional transport ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp900193e
更新日期:2010-04-05 00:00:00
abstract::Despite significant potential of oligonucleotides (ONs) for therapeutic and diagnostic applications, rapid and widespread intracellular delivery of ONs in cells situated in tissues such as skin, head and neck cavity, and eye has not been achieved. This study was aimed at evaluating the synergistic combination of micro...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp300717f
更新日期:2013-08-05 00:00:00
abstract::Recent studies on aqueous supersaturated lipophilic drug solutions prepared by methods including antisolvent addition, pH swing, or dissolution of amorphous solid dispersions (ASDs) have demonstrated that when crystallization is slow, these systems undergo liquid-liquid phase separation (LLPS) when the concentration o...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.6b00202
更新日期:2016-06-06 00:00:00
abstract::This paper develops a structure-activity relationship understanding of the way in which surfactant-like dendrons with hydrophilic spermine surface groups and a variety of lipophilic units at their focal points can self-assemble and subsequently bind to DNA with high affinity. The choice of functional group at the foca...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp100260c
更新日期:2011-04-04 00:00:00
abstract::Colistin has been increasingly used for the treatment of respiratory infections caused by Gram-negative bacteria. Unfortunately parenteral administration of colistin can cause severe adverse effects. This study aimed to develop an inhaled combination dry powder formulation of colistin and rifapentine for the treatment...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp500586p
更新日期:2015-08-03 00:00:00
abstract::Lipophilic cations such as phosphonium salts can accumulate in mitochondria of heart in response to the negative inner-transmembrane potentials. Two phosphonium salts [(18)F]FMBTP and [(18)F]mFMBTP were prepared and evaluated as potential myocardial perfusion imaging (MPI) agents in this study. The cations were radiol...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp500216g
更新日期:2014-11-03 00:00:00
abstract::Amphotericin B is a lifesaving polyene antibiotic used in the treatment of systemic mycoses. Unfortunately, the pharmacological applicability of this drug is limited because of its severe toxic side effects. At the same time, the lack of a well-defined mechanism of selectivity hampers the efforts to rationally design ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.8b00572
更新日期:2018-09-04 00:00:00
abstract::There is current interest in harnessing the combined anticancer and immunological effect of nanoparticles (NPs) and RNA. Here, we evaluate the bioactivity of poly I:C (pIC) RNA, bound to anticancer zinc oxide NP (ZnO-NP) against melanoma. Direct RNA association to unfunctionalized ZnO-NP is shown by observing change i...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.6b00795
更新日期:2017-03-06 00:00:00
abstract::Folate receptor (FR) targeting is an attractive strategy for nuclear imaging of cancer and activated macrophages through application of folic acid radioconjugates. However, significant renal accumulation of folate radioconjugates and hence exceedingly high emission of radiation from the kidneys may mask uptake of radi...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp300428p
更新日期:2013-03-04 00:00:00