Abstract：
PURPOSE:The aim of the study was to evaluate organogel nanoparticles as a lipophilic vehicle to increase the oral bioavailability of poorly soluble compounds. Efavirenz (EFV), a Biopharmaceutical Classification System (BCS) Class II, was used as drug model. METHODS:Organogel nanoparticles loaded with EFV were formulated with sunflower oil, 12-hydroxystearic acid (HSA) and polyvinyl alcohol (PVA). Various parameters have been investigated in the current study such as (i) the release profile of organogel assessed by USP 4 cell flow dialysis, (ii) the impact of organogel on intestinal absorption, using Caco-2 cells as in vitro model and jejunum segments as ex vivo assay and (iii) the bioavailability of organogel following oral pharmacokinetic study. RESULTS:250-300 nm spherical particles with a final concentration of 4.75 mg/mL drug loading were obtained, corresponding to a thousand fold increase in EFV solubility, combined to a very high encapsulation efficiency (>99.8%). Due to rapid diffusion, drug was immediately released from the nanoparticles. The biopharmaceutical evaluation on ex vivo jejunum segments demonstrated an increased absorption of EFV from organogel nanoparticles compare to a native EFV suspension. In vitro assays combining Caco-2 cell cultures with TEM and confocal microscopy demonstrated passive diffusion, while paracellular integrity and endocytosis activity remain expelled. Oral pharmacokinetics of EFV organogel nanoparticles improve oral bioavailability (Fr: 249%) and quick absorption compared to EFV suspension. CONCLUSION:Organogel nanoparticles increase the bioavailability of BCS Class II drugs. The main phenomena is simply oil transfer from the gelled particles through the cell membrane.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Martin B,Garrait G,Beyssac E,Goudouneche D,Perez E,Franceschi Sdoi
10.1007/s11095-020-02808-wsubject
Has Abstractpub_date
2020-05-11 00:00:00pages
92issue
6eissn
0724-8741issn
1573-904Xpii
10.1007/s11095-020-02808-wjournal_volume
37pub_type
杂志文章abstract：:A novel method of dipeptide synthesis is described that can be carried out in aqueous solution and does not require complicated protecting and deprotecting procedures. An analgesic neuropeptide named kyotorphin, H-Tyr-Arg-OH, was synthesized from unprotected tyrosine and arginine in a new enzymatic reaction catalyzed ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016479305603
更新日期：1987-04-01 00:00:00
abstract：PURPOSE:To characterize the pharmacokinetics of simvastatin (SV) and simvastatin acid (SVA), a lactone-acid pair known to undergo reversible metabolism, and to better understand mechanisms underlying pharmacokinetic interactions observed between SV and gemfibrozil. METHODS:Pharmacokinetic studies were conducted after ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-6037-2
更新日期：2005-07-01 00:00:00
abstract：:The plasma concentration-time profiles and pharmacokinetics were characterized for nicotine and its major metabolite, cotinine, after multiple daily application of a nicotine user-activated transdermal therapeutic system (UATTS) to nine healthy smokers. The volunteers abstained from smoking 24 hr prior to and during t...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015810019076
更新日期：1991-03-01 00:00:00
abstract：PURPOSE:We have already demonstrated that the HMG-CoA reductase inhibitor, pravastatin is actively taken up by isolated rat hepatocytes via a multispecific anion transporter (Yamazaki et al., Am. J. Physiol. 264, G36-44, (1993)). We further attempted the quantitative evaluation of this uptake in different experimental ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016226024587
更新日期：1995-11-01 00:00:00
abstract：PURPOSE:The in-situ particle size of delavirdine mesylate in dry mix and tablets was determined. METHODS:Optical microscopy and fluorescence microscopy combined with image analysis were used for qualitative and quantitative measurements. RESULTS:Using optical microscopy, it was demonstrated qualitatively that fragmen...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018875130152
更新日期：1999-04-01 00:00:00
abstract：:Cyclosporine (CsA) is commercially available for oral administration as a solution in olive oil with alcohol and an emulsifier. To improve its variable absorption and low patient acceptability, several oral formulations were prepared and tested in vitro and in vivo in dogs. A tablet formulation prepared by direct comp...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015815614959
更新日期：1991-04-01 00:00:00
abstract：:The glass transition temperature of an amorphous pharmaceutical solid is a critical physical property which can dramatically influence its chemical stability, physical stability, and viscoelastic properties. Water frequently acts as a potent plasticizer for such materials, and since many amorphous solids spontaneously...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018941810744
更新日期：1994-04-01 00:00:00
abstract：:The effect of different concentrations of polyvinyl alcohol 14000 and 72000 (PVA 14 and 72) on the activity of betamethasone and phenylephrine hydrochloride in the rabbit eye was investigated. The polymer of higher molecular weight exerts a more pronounced effect at relatively lower viscosities. Effects on the intraoc...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016398915965
更新日期：1986-08-01 00:00:00
abstract：PURPOSE:Nanocrystalline drug-polymer dispersions are of significant interest in pharmaceutical delivery. The purpose of this work is to demonstrate the applicability of methods based on two-dimensional (2D) and multinuclear solid-state NMR (SSNMR) to a novel nanocrystalline pharmaceutical dispersion of ebselen with pol...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0713-9
更新日期：2012-07-01 00:00:00
abstract：PURPOSE:The aim of this study was to investigate the depth-dependent intradermal immunogenicity of inactivated polio vaccine (IPV) delivered by depth-controlled microinjections via hollow microneedles (HMN) and to investigate antibody response enhancing effects of IPV immunization adjuvanted with CpG oligodeoxynucleoti...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-1965-6
更新日期：2016-09-01 00:00:00
abstract：PURPOSE:Poly-L-arginine (PLA) enhances the paracellular permeability of the Caco-2 cell monolayer to hydrophilic macromolecules by disappearance of tight junction (TJ) proteins from cell-cell junctions. However, the mechanism of the disappearance of TJ proteins in response to PLA has been unclear. In this study, we inv...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1324-4
更新日期：2014-09-01 00:00:00
abstract：PURPOSE:This work explores the distribution of water and its effects on molecular mobilities in poly(vinylpyrrolidone) (PVP) glasses using molecular dynamics (MD) simulation technology. METHODS:PVP glasses containing 0.5% and 10% w/w water and a small amount of ammonia and Phe-Asn-Gly were generated. Physical aging pr...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-5277-5
更新日期：2005-08-01 00:00:00
abstract：PURPOSE:Grapefruit juice (GJ) is known to increase the oral bioavailability of many CYP3A-substrates by inhibiting intestinal phase-I metabolism. However, the magnitude of AUC increase is often insignificant and highly variable. Since we earlier suggested that CYP3A and P-glycoprotein (P-gp) form a concerted barrier to...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011902625609
更新日期：1999-04-01 00:00:00
abstract：PURPOSE:To develop a method for drawing statistical inferences from differences between multiple experimental pair distribution function (PDF) transforms of powder X-ray diffraction (PXRD) data. METHODS:The appropriate treatment of initial PXRD error estimates using traditional error propagation algorithms was tested ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-010-0259-7
更新日期：2010-12-01 00:00:00
abstract：:An oral formulation of controlled-release isosorbide-5-nitrate pellets has been used to investigate the location of pellets in the gastrointestinal (GI) tract and, in parallel, to measure the drug absorption from these locations. Using the method of gamma scintigraphy the transit times and spreading of pellets in the ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016423404636
更新日期：1987-12-01 00:00:00
abstract：PURPOSE:To analyze the effects of chemical enhancers and iontophoresis on the buccal transmucosal delivery of lidocaine and nicotine. METHODS:Porcine oral mucosal samples were pretreated with chemical enhancers before conducting 8-hr Franz diffusion-cell experiments. In studies addressing the influence of iontophoresi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0636-x
更新日期：2012-04-01 00:00:00
abstract：OBJECTIVE:Amorphous pharmaceuticals, a viable approach to enhancing bioavailability, must be stable against crystallization. An amorphous drug can be stabilized by dispersing it in a polymer matrix. To implement this approach, it is desirable to know the drug's solubility in the chosen polymer, which defines the maxima...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9784-z
更新日期：2009-04-01 00:00:00
abstract：PURPOSE:Topoisomerase II (Topo II) preferentially cuts DNA at alternating purine-pyrimidine repeats. Different Topo II poisons may affect Topo II to produce distinct drug-specific DNA cleavage patterns. GL331 is a new podophyllotoxin derivative exhibiting potent Topo II-poisoning activity. Therefore, the sequence selec...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011048831698
更新日期：2001-06-01 00:00:00
abstract：PURPOSE:Orally absorbable anticancer medications have great advantages for conventional cancer therapies to patients. Here we evaluated the potent anticancer effect of orally absorbable LHD, a chemical conjugate of low-molecular-weight heparin and deoxycholic acid, on tumor graft growth models. METHODS:We characterize...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-9989-9
更新日期：2009-12-01 00:00:00
abstract：:A new enteric-coated formulation of sodium ursodeoxycholate was prepared and administered to man. The barrier film disintegrates and releases the drug only at pH > or = 5.5. The sodium salt of glycoursodeoxycholate was also prepared and encapsulated like ursodeoxycholate. Serum levels of ursodeoxycholate and glycourso...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018907825281
更新日期：1994-05-01 00:00:00
abstract：:Gene delivery vectors based on adeno-associated virus (AAV) are highly promising due to several desirable features of this parent virus, including a lack of pathogenicity, efficient infection of dividing and non-dividing cells, and sustained maintenance of the viral genome. However, several problems should be addresse...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-007-9431-0
更新日期：2008-03-01 00:00:00
abstract：PURPOSE:We investigated optimum formulation characteristics in the nasal absorption of salmon calcitonin (sCT) by incorporation of acylcarnitines. METHODS:Nasal sCT formulations were administered to anesthetized rats. Plasma calcium level was measured and pharmacological bioavailability (P.bioav) was calculated. RESU...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016051600828
更新日期：1996-05-01 00:00:00
abstract：PURPOSE:Biomaterials which release locally high concentrations of antithrombotic agents should lessen the thrombogenicity of the materials. To evaluate this approach, we prepared novel polyurethane matrices loaded with hirudin and coated them with 2-hydroxyethyl methacrylate (HEMA) by glow discharge plasma deposition (...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011987423502
更新日期：1998-05-01 00:00:00
abstract：PURPOSE:Adenoviruses are being developed for diseases of the gastrointestinal tract. Several in vitro assays were used to predict stability of PEGylated adenovirus along the GI tract and determine in vivo gene transfer after oral administration. METHODS:Recombinant adenovirus was modified with monomethoxypoly(ethylene...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1025714412337
更新日期：2003-09-01 00:00:00
abstract：PURPOSE:Nonlinear conjugation metabolic rate of valproic acid (VPA) has been speculated previously from plasma elimination and liver concentration of VPA in guinea pigs. The purposes of the present study were to assess our speculation by direct measurement of VPA glucuronidation rate in vitro. METHODS:VPA at various c...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016028707130
更新日期：1996-08-01 00:00:00
abstract：PURPOSE:Excipients are added to lyophilized protein drug formulations to protect the protein during processing and storage, but the mechanisms are poorly understood. Here, hydrogen/deuterium (H/D) exchange with mass spectrometry was used to assess protein conformation and excipient interactions in lyophilized solids. ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9365-6
更新日期：2008-02-01 00:00:00
abstract：PURPOSE:To examine the transport characteristics of the multidrug resistance-associated protein (MRP) substrate fluorescein across the isolated rat small intestinal segments. METHODS:The transport of fluorescein was studied in side-by-side diffusion chambers under short-circuited conditions at physiological pH. RESUL...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000022410.89709.c3
更新日期：2004-04-01 00:00:00
abstract：:The influence of the jejunal bloodflow on the absorption of theophylline was investigated. The bloodflow through a segment under investigation was varied by changing the systemic blood pressure by means of a donor blood infusion into the jugular vein or by an infusion of isoprenaline or levarterenol into a femoral vei...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016374508542
更新日期：1984-01-01 00:00:00
abstract：PURPOSE:Three types of acyl tetragastrin (TG), acetyl-TG (C2-TG), butyryl-TG (C4-TG) and caproyl-TG (C6-TG) were synthesized and their in vitro intestinal permeability characteristics were examined using Caco-2 monolayers. METHODS:The disappearance of acyl-TGs from the apical side of Caco-2 monolayers was estimated by...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011997404306
更新日期：1998-09-01 00:00:00
abstract：PURPOSE:Reverse iontophoresis is an alternative to blood sampling for the monitoring of endogenous molecules. Here, the potential of the technique to measure urea and potassium levels non-invasively, and to track their concentrations during hemodialysis, has been examined. MATERIALS AND METHODS:In vitro experiments we...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9237-0
更新日期：2007-06-01 00:00:00
