Abstract:
:Lipid-based drug delivery systems have been vastly investigated as a pharmaceutical method to enhance oral absorption of lipophilic drugs. However, these vehicles not only affect drug bioavailability but may also have an impact on gastric emptying, drug disposition, lymphatic absorption and be affected by lipid digestion mechanisms. The work presented here compared the pharmacokinetic (PK) behavior of the non-intoxicating cannabinoid cannabidiol (CBD) in sesame oil vs. a self-nano emulsifying drug delivery system (SNEDDS). This investigation was conducted with a unique tool termed the "absorption cocktail approach". In this concept, selected molecules: metoprolol, THC, and ibuprofen, were coadministered with CBD in the SNEDDS and sesame oil. This method was used to shed light on the complex absorption process of poorly soluble drugs in vivo, specifically assessing the absorption kinetics of CBD. It was found that the concentration vs. time curve following CBD-sesame oil oral administration showed extended input of the drug with a delayed Tmax compared to CBD-SNEDDS. Using the "cocktail" approach, a unique finding was observed when the less lipophilic compounds (metoprolol and ibuprofen) exited the stomach much earlier than the lipophilic cannabinoids in sesame oil, proving differential absorption kinetics. Findings of the absorption cocktail approach reflected the physiological process of the GI, e.g., gastric retention, stomach content separation, lipid digestion, drug precipitation and more, demonstrating its utility. Nonetheless, the search for more compounds as suitable probes is underway.
journal_name
Mol Pharmjournal_title
Molecular pharmaceuticsauthors
Izgelov D,Regev A,Domb AJ,Hoffman Adoi
10.1021/acs.molpharmaceut.0c00141subject
Has Abstractpub_date
2020-06-01 00:00:00pages
1979-1986issue
6eissn
1543-8384issn
1543-8392journal_volume
17pub_type
杂志文章abstract::Solid-state hydrogen-deuterium exchange with mass spectrometric analysis (ssHDX) is a promising method for characterizing proteins in amorphous solids. Though analysis of HDX kinetics is informative and well-established in solution, application of these methods to solid samples is complicated by possible heterogeneiti...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp2004093
更新日期:2012-04-02 00:00:00
abstract::In this study, the photochemical internalization (PCI) technique was adopted in a nanoparticle-based antigen delivery system to enhance antigen-specific CD8+ T cell immune response for cancer immunotherapy. Pheophorbide A, a hydrophobic photosensitizer, grafted with polyethylenimine (PheoA-PEI) with endosome escape ac...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00015
更新日期:2017-05-01 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::5-Fluorocytosine (FC), an antifungal drug and a cytosine derivative, has a complex solid-state landscape that challenges its development into a drug product. A total of eight new FC salts, both cytosinium and hemicytosinium, with four strong acids were prepared by controlling acid concentration in the crystallization ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp400070a
更新日期:2013-06-03 00:00:00
abstract::Reversible aqueous lipidization (REAL) at the interdisulfide bond has been shown to improve the deliverability of some peptide drugs. Recently, we developed a nonreversible aqueous lipidization method targeted at the interdisulfide bond of salmon calcitonin (sCT). The resultant derivative had comparable hypocalcemic a...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp8000167
更新日期:2008-07-01 00:00:00
abstract::Deferoxamine mesylate (DFO) is an FDA-approved, hexadentate iron chelator routinely used to alleviate systemic iron burden in thalassemia major and sickle cell patients. Iron accumulation in these disease states results from the repeated blood transfusions required to manage these conditions. Iron accumulation has als...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.0c00474
更新日期:2021-02-01 00:00:00
abstract::Powder adhesion or sticking onto punches is one of the outstanding issues in pharmaceutical tablet manufacturing. We show in this work that, at comparable particle sizes, the acesulfame potassium exhibited pronouncedly reduced propensity to punch sticking than acesulfame. Detailed analyses revealed strong correlation ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b00247
更新日期:2019-06-03 00:00:00
abstract::Poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-b-PLA) micelles have a proven capacity for drug solubilization and have entered phase III clinical trials as a substitute for Cremophor EL in the delivery of paclitaxel in cancer therapy. PEG-b-PLA is less toxic than Cremophor EL, enabling a doubling of paclitaxel...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp2000549
更新日期:2011-08-01 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::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::Efficient drug delivery to the skin is essential for the treatment of major dermatologic diseases, such as eczema, psoriasis and acne. However, many compounds penetrate the skin barrier poorly and require optimized formulations to ensure their bioavailability. Here, stimulated Raman scattering (SRS) microscopy, a rece...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp200122w
更新日期:2011-06-06 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
abstract::OATP1B3 is a member of the OATP (organic anion transporting polypeptides) superfamily, responsible for mediating the transport of numerous endogenous and xenobiotic substances. Although initially reported to be exclusively expressed in the liver, several studies reported that OATP1B3 is frequently expressed in multipl...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp3005353
更新日期:2013-01-07 00:00:00
abstract::We report on the fabrication and characterization of dry hybrid lipid-silica nanoparticle based microcapsules with an internal porous matrix structure for encapsulation of poorly soluble drugs, and their delivery properties (in vitro release and lipolysis and in vivo pharmacokinetics demonstrated for indomethacin as a...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp900063t
更新日期:2009-05-01 00:00:00
abstract::The objective of this work was to investigate the feasibility of using a novel granulation technique, namely, fluidized hot melt granulation (FHMG), to prepare gastroretentive extended-release floating granules. In this study we have utilized FHMG, a solvent free process in which granulation is achieved with the aid o...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp500242q
更新日期:2014-10-06 00:00:00
abstract::Because of its biocompatibility and ability to accommodate a variety of payloads from poorly soluble drugs to biomolecules, porous silicon (PSi) is a lucrative material for the development of carriers for particle-mediated drug delivery. We report a successful direct one-step (18)F-radiolabeling of three types of PSi ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp2001654
更新日期:2011-10-03 00:00:00
abstract::Active targeting of nanostructures containing chemotherapeutic agents can improve cancer treatment. Here, a three-way junction pocket DNA nanostructure was developed for efficient doxorubicin (Dox) delivery into cancer cells. The three-way junction pocket DNA nanostructure is composed of three strands of AS1411 aptame...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.8b00124
更新日期:2018-05-07 00:00:00
abstract::Conjugation with a cell penetrating peptide such as Tat presents an effective approach to improve the intracellular accumulation of molecules with low membrane permeability. This strategy, however, leads to a reduced cellular entry of molecules that can cross cell membrane effectively. We report here that covalent lin...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp400619v
更新日期:2014-03-03 00:00:00
abstract::In this study, the dissolution properties of celecoxib (CX) solid dispersions manufactured from Eudragit 4155F and polyvinylpyrrolidone (PVP) were evaluated. Hot-melt extrusion (HME) technology was used to prepare amorphous solid dispersions of drug/polymer binary systems at different mass ratios. The drug concentrati...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp200157b
更新日期:2011-08-01 00:00:00
abstract::As the hearts of tumor cells, the nucleus is the ultimate target of many chemotherapeutic agents and genes. However, nuclear drug delivery is always hampered by multiple intracellular obstacles, such as low efficiency of lysosome escape and insufficient nuclear trafficking. Herein, an N-(2-hydroxypropyl) methacrylamid...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.6b00181
更新日期:2016-09-06 00:00:00
abstract::One hallmark of neuroinflammation is the activation of microglia, which triggers the production and release of reactive oxygen species (ROS), nitrate, nitrite, and cytokines. N-Acetyl cysteine (NAC) is a free radical scavenger that is involved in the intracellular and extracellular detoxification of reactive oxygen sp...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.6b01028
更新日期:2017-05-01 00:00:00
abstract::Solid-state NMR (SSNMR) (1)H T1 and T1ρ relaxation times were used to evaluate the miscibility of amorphous solid dispersions of nifedipine (NIF) and polyvinylpyrrolidone (PVP) prepared by three different methods: melt quenching in the typical lab setting, spray drying and melt quenching in the NMR rotor while spinnin...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp400498n
更新日期:2014-01-06 00:00:00
abstract::Photodynamic therapy (PDT) is promising for clinical cancer therapy; however, the efficacy was limited as an individual treatment regimen. Here, an approach synergistically combining PDT and nitric oxide (NO) gas therapy along with destruction of the tumor extracellular matrix (ECM) was presented to eliminate cancer. ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.0c00937
更新日期:2021-01-11 00:00:00
abstract::For the purpose of improving the tumor delivery of doxorubicin (DOX), a kind of peptide-DOXO conjugate was designed and prepared, in which the peptide composed of an albumin-binding domain (ABD) and a tumor-specific internalizing sequence (RGDK or RPARPAR) was conjugated to a (6-maleimidocaproyl) hydrazone derivative ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00497
更新日期:2017-11-06 00:00:00
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-equilibriu...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp3003495
更新日期:2012-11-05 00:00:00
abstract::The mechanism of cell death in A2780 human ovarian carcinoma cells induced by free doxorubicin (DOX) and N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-bound DOX [P-(GFLG)-DOX] was investigated. In particular, the involvement of the Fas receptor system in drug-induced apoptosis was evaluated. P-(GFLG)-DOX was show...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp049967q
更新日期:2004-05-01 00:00:00
abstract::Amino acids derivative are well established molecular probes for diagnosis of a variety of cancer using positron emission tomography (PET). Recently, boramino acid (BAAs) was found as a prospective molecular platform for developing PET tracer. The objective of this study was to develop a 18F-labeled alanine derivative...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00884
更新日期:2018-03-05 00:00:00
abstract::Erythropoietin (EPO), a hematopoietic growth factor and a promising therapy for Alzheimer's disease, has low permeability across the blood-brain barrier. The transferrin receptor antibody fused to EPO (TfRMAb-EPO) is a chimeric monoclonal antibody that ferries EPO into the brain via the transvascular route. However, T...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.0c00231
更新日期:2020-08-03 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:BACKGROUND:For the development of novel buccoadhesive formulations, their physicochemical properties, strength of the interfacial joint, and residence time on the buccal mucosa are considered as a measure for their in vivo mucoadhesive properties. Focusing on these parameters, the predictive power of established in vit...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b00254
更新日期:2019-06-03 00:00:00