Search results for "Bioavailability"
showing 10 items of 301 documents
Influence of landscape composition and diversity on contaminant flux in terrestrial food webs: a case study of trace metal transfer to European black…
2012
13 pages; International audience; Although understanding the influence of the spatial arrangement of habitats and interacting communities on the processes of pollutant flux and impacts is critical for exposure and risk assessment, to date few studies have been devoted to this emergent topic. We tested the hypothesis that landscape composition and diversity affect the transfer of trace metals to vertebrates. Bioaccumulation of Cd and Pb in blood and feathers of European blackbirds Turdus merula (n=138) was studied over a smelter-impacted area (Northern France). Landscape composition (type and occurrence of the different habitats) and diversity (number of different habitat types and the propo…
Ion Pairing with Bile Salts Modulates Intestinal Permeability and Contributes to Food–Drug Interaction of BCS Class III Compound Trospium Chloride
2013
In the current study the involvement of ion pair formation between bile salts and trospium chloride (TC), a positively charged Biopharmaceutical Classification System (BCS) class III substance, showing a decrease in bioavailability upon coadministration with food (negative food effect) was investigated. Isothermal titration calorimetry provided evidence of a reaction between TC and bile acids. An effect of ion pair formation on the apparent partition coefficient (APC) was examined using (3)H-trospium. The addition of bovine bile and bile extract porcine led to a significant increase of the APC. In vitro permeability studies of trospium were performed across Caco-2-monolayers and excised seg…
Δ5-Cholenoyl-amino acids as selective and orally available antagonists of the Epheephrin system
2015
The Eph receptor-ephrin system is an emerging target for the development of novel anti-angiogenic therapies. Research programs aimed at developing small-molecule antagonists of the Eph receptors are still in their initial stage as available compounds suffer from pharmacological drawbacks, limiting their application in vitro and in vivo. In the present work, we report the design, synthesis and evaluation of structure-activity relationships of a class of Δ(5)-cholenoyl-amino acid conjugates as Eph-ephrin antagonists. As a major achievement of our exploration, we identified N-(3β-hydroxy-Δ(5)-cholen-24-oyl)-L-tryptophan (UniPR1331) as the first small molecule antagonist of the Eph-ephrin syste…
Antihypertensive properties of lactoferricin B-derived peptides.
2010
A set of eight lactoferricin B (LfcinB)-derived peptides was examined for inhibitory effects on angiotensin I-converting enzyme (ACE) activity and ACE-dependent vasoconstriction, and their hypotensive effect in spontaneously hypertensive rats (SHR). Peptides were derived from different elongations both at the C-terminal and N-terminal ends of the representative peptide LfcinB(20-25), which is known as the LfcinB antimicrobial core. All of the eight LfcinB-derived peptides showed in vitro inhibitory effects on ACE activity with different IC(50) values. Moreover, seven of them showed ex vivo inhibitory effects on ACE-dependent vasoconstriction. No clear correlation between in vitro and ex viv…
Ocular tolerability and in vivo bioavailability of poly(ethylene glycol) (PEG)-coated polyethyl-2-cyanoacrylate nanosphere-encapsulated acyclovir.
2001
Acyclovir-loaded polyethyl-2-cyanoacrylate (PECA) nanospheres were prepared by an emulsion polymerization process in the micellar phase and characterized. The influence of the presence of nonionic surfactant as well as other substances [i.e., 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) and poly(ethylene glycol) (PEG)], on formulation parameters and loading capacity was investigated. In particular, the presence of PEG resulted in an increase of mean size and size distribution. To obtain PEG-coated PECA nanospheres with a mean size of200 nm, Pluronic F68 at concentrations1.5% (w/v) should be used during preparation. The presence of PEG also resulted in a change in zeta potential, from -25…
The effects of three absorption-modifying critical excipients on the in vivo intestinal absorption of six model compounds in rats and dogs.
2018
Pharmaceutical excipients that may affect gastrointestinal (GI) drug absorption are called critical pharmaceutical excipients, or absorption-modifying excipients (AMEs) if they act by altering the integrity of the intestinal epithelial cell membrane. Some of these excipients increase intestinal permeability, and subsequently the absorption and bioavailability of the drug. This could have implications for both the assessment of bioequivalence and the efficacy of the absorption-enhancing drug delivery system. The absorption-enhancing effects of AMEs with different mechanisms (chitosan, sodium caprate, sodium dodecyl sulfate (SDS)) have previously been evaluated in the rat single-pass intestin…
INULIN BASED HYDROGEL FOR ORAL DELIVERY OF FLUTAMIDE: PREPARATION, CHARACTERIZATION AND IN VIVO RELEASE STUDIES
2012
The ability of a hydrogel obtained by crosslinking INUDV and PEGBa to facilitate sustained release of flutamide is examined. The hydrogel is prepared in pH = 7.4 PBS and no toxic solvents or catalysts are used. It is recovered in microparticulate form and its size distribution is determined. Mucoadhesive properties are evaluated in vitro by reproducing gastrointestinal conditions. Flutamide is loaded into the hydrogel using a post-fabrication encapsulation procedure that allows a drug loading comparable to that of market tablets. Drug-loaded microparticles are orally administered to cross-bred dogs and the in vivo study demonstrates their ability to prolong the half-life of the principal ac…
Extended release and enhanced bioavailability of moxifloxacin conjugated with hydrophilic cellulose ethers.
2015
Macromolecular prodrugs (MPDs) of moxifloxacin were fabricated based on hydroxypropylcellulose (HPC) and hydroxyethylcellulose (HEC). UV/Vis spectrophotometry was employed to determine covalently loaded drug content (DC) of each conjugate. The degree of substitution (DS) of moxifloxacin attained ranged from 0.27 to 0.38 (HPC) and 0.19 to 0.26 (HEC) per anhydroglucose unit (AGU), respectively. Transmission electron microscopic analyses showed that HPC-moxifloxacin conjugates self-assembled into nanowires of ∼ 30 nm diameters while HEC-moxifloxacin conjugates self-assembled into nanoparticles of 150-350 nm. In vitro drug release studies revealed that 15 and 49% moxifloxacin release occurred f…
Polyhydroxyethylaspartamide-based micelles for ocular drug delivery
2009
In this paper three copolymers of polyhydroxyethylaspartamide (PHEA), bearing in the side chains polyethylene glycol (PEG) and/or hexadecylamine (C(16)) (PHEA-PEG, PHEA-PEG-C(16) and PHEA-C(16) respectively) have been studied as potential colloidal drug carriers for ocular drug delivery. The physical characterization of all three PHEA derivatives, using the Langmuir trough (LT) and micellar affinity capillary electrophoresis (MACE) techniques allowed to assume that whereas alone PHEA backbone is an inert polymer with respect to the interactions with lipid membranes and drug complexation, when PHEA chains are grafted with long alkyl chains like C(16) or in combination C(16) chains and hydrop…
Influence of polymer molecular weight on in vitro dissolution behavior and in vivo performance of celecoxib:PVP amorphous solid dispersions
2016
In this study, the influence of the molecular weight of polyvinylpyrrolidone (PVP) on the non-sink in vitro dissolution and in vivo performance of celecoxib (CCX):PVP amorphous solid dispersions were investigated. The dissolution rate of CCX from the amorphous solid dispersions increased with decreasing PVP molecular weight and crystallization inhibition was increased with increasing molecular weight of PVP, but reached a maximum for PVP K30. This suggested that the crystallization inhibition was not proportional with molecular weight of the polymer, but rather there was an optimal molecular weight where the crystallization inhibition was strongest. Consistent with the findings from the non…