Abstract:
:In this work, we investigated the relationship between various intermolecular hydrogen-bonding (H-bonding) interactions and the miscibility of the model hydrophobic drug naproxen with the hydrophilic polymer polyvinylpyrrolidone (PVP) across an entire composition range of solid dispersions prepared by quasi-equilibrium film casting and nonequilibrium melt quench cooling. The binary phase behavior in solid dispersions exhibited substantial processing method dependence. The solid state solubility of crystalline naproxen in PVP to form amorphous solid dispersions was 35% and 70% w/w naproxen in solution-cast films and quench-cooled films, respectively. However, the presence of a single mixed phase glass transition indicated the amorphous miscibility to be 20% w/w naproxen for the films, beyond which amorphous-amorphous and/or crystalline phase separations were apparent. This was further supported by the solution state interactions data such as PVP globular size distribution and solution infrared spectral profiles. The borderline melt composition showed cooling rate dependence of amorphization. The glass transition and melting point depression profiles of the system were treated with the analytical expressions based on Flory-Huggins mixing theory to interpolate the equilibrium solid solubility. FTIR analysis and subsequent spectral deconvolution revealed composition and miscibility dependent variations in the strength of drug-polymer intermolecular H-bonding. Two types of H-bonded populations were evidenced from 25% w/w and 35% w/w naproxen in solution-cast films and quench-cooled films, respectively, with the higher fraction of strongly H-bonded population in the drug rich domains of phase separated amorphous film compositions and highly drug loaded amorphous quench-cooled dispersions.
journal_name
Mol Pharmjournal_title
Molecular pharmaceuticsauthors
Paudel A,Nies E,Van den Mooter Gdoi
10.1021/mp3003495subject
Has Abstractpub_date
2012-11-05 00:00:00pages
3301-17issue
11eissn
1543-8384issn
1543-8392journal_volume
9pub_type
杂志文章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
abstract::Combinatorial chemistry has enabled the production of very potent drugs that might otherwise suffer from poor solubility and low oral bioavailability. One approach to increase solubility is to make the drug amorphous, which leads to problems associated with drug stability. To improve stability, one option is to molecu...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp400712m
更新日期:2014-07-07 00:00:00
abstract::Design and development of amphiphilic block copolymer-based nanocarriers exhibiting enhanced colloidal stability upon dilution in the blood and cellular glutathione-responsive rapid drug release is highly desired for tumor-targeting chemotherapy. Herein, we report a novel ABA-type triblock copolymer consisting of a hy...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.6b01146
更新日期:2017-08-07 00:00:00
abstract::In our previous studies, ethylene glycol-linked amino acid diester prodrugs of oleanolic acid (OA), a Biopharmaceutics Classification System (BCS) class IV drug, designed to target peptide transporter 1 (PepT1) have been synthesized and evaluated. Unlike ethylene glycol, propylene glycol is of very low toxicity in viv...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp300647m
更新日期:2013-04-01 00:00:00
abstract::In vivo peptide inhibition of tumor suppressor p53 binding to the protein MDM2 is hampered by inefficient delivery of the peptide. Our approach to couple a hydrophobic lipid-like tail on the inhibitory peptide p53(14-29) allowed its intracellular delivery in vitro, in a panel of different cell lines. The constructed c...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp100193h
更新日期:2010-12-06 00:00:00
abstract::Solvation of drugs in the core (C) and headgroup (H) strata of phospholipid bilayers affects their physiological transport rates and accumulation. These characteristics, especially a complete drug distribution profile across the bilayer strata, are tedious to obtain experimentally, to the point that even simplified pr...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp5003366
更新日期:2014-10-06 00:00:00
abstract::For aggressive brain glioblastoma, the therapy is significantly impaired by blood-brain barrier (BBB) and blood-tumor barrier (BTB). Choosing more than one target from the pool of tumor-stroma interactions is profoundly beneficial to therapeutic approaches. Thus, a multifunctional liposomal system based on anchoring t...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.6b00819
更新日期:2017-04-03 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::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::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::Some specific types of tumor cells and tumor endothelial cells represented CD13 proteins and act as receptors for Asn-Gly-Arg (NGR) motifs containing peptide. These CD13 receptors can be specifically recognized and bind through the specific sequence of cyclic NGR (cNGR) peptide and presented more affinity and specific...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp400404p
更新日期:2014-03-03 00:00:00
abstract::Solubility limited compounds require enabling formulations such as amorphous solid dispersions (ASDs) to increase the apparent solubility by dissolving to a concentration higher than the equilibrium solubility of the drug. This may lead to subsequent precipitation and thus the loss of the solubility advantage. Althoug...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.6b00788
更新日期:2017-01-03 00:00:00
abstract::Indocyanine green (ICG) is a conventional dye that can be used in clinical near-infrared (NIR) imaging, and it is also an effective light absorber for laser-mediated photothermal therapy. However, applications of ICG were limited due to its fast degradation in aqueous media and quick clearance from the body. Herein, a...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp200526m
更新日期:2012-03-05 00:00:00
abstract::Diagnostic imaging of the liver by ultrasound, computed tomography (CT) and magnetic resonance tomography (MRT) is generally limited to the visualization of the morphology. In order to exploit the intriguing liver tropism of the human hepatitis B virus (HBV) for molecular imaging of the liver, peptidic tracers derived...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp400038r
更新日期:2013-06-03 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::Cationic poly-L-lysine 3H-dendrimers with either 16 or 32 surface amine groups (BHALys [Lys]4 [3H-Lys]8 [NH2]16 and BHALys [Lys]8 [3H-Lys]16 [NH2]32, generation 3 and 4, respectively) have been synthesized and their pharmacokinetics and biodistribution investigated after intravenous administration to rats. The species...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp060032e
更新日期:2006-09-01 00:00:00
abstract::Hydrophilic peptides constitute most of the active peptides. They mostly permeate via tight junctions (paracellular pathway) in the intestine. This permeability mechanism restricts the magnitude of their oral absorption and bioavailability. We hypothesized that concealing the hydrophilic residues of the peptide using ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.8b00466
更新日期:2018-08-06 00:00:00
abstract::Deacetylated gellan gum and two sodium alginate polymer types were used each at three concentrations in the suitable range for their sol-gel transition. The prepared nine droppable gels were evaluated in vitro, ex vivo through sheep nasal mucosa, as well as in vivo in comparison to drug solution given intravenously an...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp500825n
更新日期:2015-06-01 00:00:00
abstract::Influenza viruses cause seasonal epidemics and represent a pandemic risk. With current vaccine methods struggling to protect populations against emerging strains, there is a demand for a next-generation flu vaccine capable of providing broad protection. Recombinant biotechnology, combined with nanomedicine techniques,...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.0c00383
更新日期:2021-02-01 00:00:00
abstract::Constitutive activation of signal transducer and activator of transcription 3 (STAT3) in tumor cells and tumor associated dendritic cells (DCs) plays a major role in the progression of cancer. JSI-124 (cucurbitacin I) is a potent inhibitor of STAT3; however, its poor solubility and nonspecificity limit its effectivene...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.6b01119
更新日期:2017-08-07 00:00:00
abstract::Whether luteolin inhibits HBV replication has not been validated and the underlying mechanism of which has never been elucidated. In this study, we show that luteolin reduces HBV DNA replication in HepG2.2.15 cells. Luteolin effectively inhibited the expression of hepatocyte nuclear factor 4α (HNF4α) and its binding t...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.5b00789
更新日期:2016-02-01 00:00:00
abstract::5P12-RANTES is a recently developed chemokine analogue that has shown high level protection from SHIV infection in macaques. However, the feasibility of using 5P12-RANTES as a long-term HIV prevention agent has not been explored partially due to the lack of available delivery devices that can easily be modified for lo...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp3007242
更新日期:2013-10-07 00:00:00
abstract::Near-infrared (NIR)-to-visible upconversion nanoparticle (UCNP) has shown promising prospects in photodynamic therapy (PDT) as a drug carrier or energy donor. In this work, a photosensitizer pyropheophorbide a (Ppa) and RGD peptide c(RGDyK) comodified chitosan-wrapped NaYF(4):Yb/Er upconversion nanoparticle UCNP-Ppa-R...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp200590y
更新日期:2012-06-04 00:00:00
abstract::A wide variety of chemotherapy and radiotherapy agents are available for treating cancer, but a critical challenge is to deliver these agents locally to cancer cells and tumors while minimizing side effects from systemic delivery. Nanomedicine uses nanoparticles with diameters in the range of ∼1-100 nm to encapsulate ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章,评审
doi:10.1021/mp400419k
更新日期:2014-01-06 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::A combination of microbubbles (MBs) and ultrasound (US) is an emerging method for noninvasive and targeted enhancement of anti-cancer drug uptake. This method showed an increase local drug extravasation in tumor tissue while reducing the systemic adverse effects in various tumor models. The present study aims to evalu...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b00416
更新日期:2019-09-03 00:00:00
abstract::High-functionality and -quality (HFQ) lipids have a discrete molecular weight and good water dispersibility and can be produced by solid-phase peptide synthesis. Therefore, HFQ lipids are a promising material for the preparation of ligand-grafted PEGylated liposomes. Recently, we have reported serine-glycine repeated ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.8b00476
更新日期:2018-10-01 00:00:00
abstract::Helicobacter pylori inhabits the gastric epithelium and can promote the development of gastric disorders, such as peptic ulcers, acute and chronic gastritis, mucosal lymphoid tissue (MALT), and gastric adenocarcinomas. To use nanotechnology as a tool to increase the antibacterial activity of silver I [Ag(I)] compounds...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b01264
更新日期:2020-07-06 00:00:00
abstract::Eight-armed PEG, molecular mass 10 kDa, was functionalized with furyl and maleimide groups, respectively; the obtained macromonomers were cross-linked via Diels-Alder chemistry. The mesh size (ξ) of the prepared hydrogels was determined by swelling studies, rheology, and low field NMR spectroscopy. The in vitro releas...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.5b00375
更新日期:2015-09-08 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