Disposition in rat of a new fluorinated, biocompatible, non-ionic telomeric carrier

Abstract

1. The disposition of the new fluorinated, biocompatible, non-ionic telomeric carrier trisacryl conjugate (F-TAC) labelled with 13C and 14C on the amide function has been studied in the rat after p.o. and i.v. administration. 2. After i.v. administration, excretion measurements have shown that radioactivity was eliminated mainly in the urine (69% within 24 h), and that faecal excretion was low (8% within 72 h). After p.o. administration, faecal elimination was significantly increased (30% within 72 h). No radioactivity was eliminated as 14CO2, after either route of administration. 3. After i.v. administration, plasma radioactivity exhibited a biphasic decrease, with t1/2 = 20 min for the first phase and 29.5 h for the second phase. The maximal plasma concentration was obtained 40 min after oral dosing, followed by a monoexponential decrease with t1/2 = 38.1 h. The ratio AUC (p.o.)/AUC (i.v.) as an assessment of bioavailability was 0.22. 4. After both i.v. and p.o. administration, a relatively homogeneous concentration of radioactivity was found in most organs, close or below the plasma concentration, indicating that tissues do not exhibit a high affinity for this molecule. In addition, F-TAC did not cross the blood-brain barrier. 5. Analysis of urine and plasma on DOWEX AG1X2 anionic resin showed that < 20% of the radioactivity was bound to this support. 13C- and 19F-nmr analysis of the non-bound radioactivity identified it to unchanged F-TAC, with bound radioactivity being due to polyanionic telomers arising from the hydrolysis of the amide function.(ABSTRACT TRUNCATED AT 250 WORDS)

An in vitro study of the sub‐cellular distribution of nicotinic receptors

“…This kind of molecule can lower the surface tension of water more than hydrocarbon-based analogues, but they do not exhibit any detergent power (Pucci et al, 1991). They have several advantages : because of their low MW (molecular weight), they should be able to cross biological membranes and no accumulation phenomenon in the organism should be noted (Maurizis et al, 1994;Chehade et al, 1996). It does not interact well with the alkyl chain of natural lipids (Barthélémy et al, 2002) but can handle integral membrane proteins in aqueous solution without any denaturation (Chabaud et al, 1998).…”

Synthesis and preliminary biological assessments of a new class of amphiphilic telomers bearing 5-fluorouracil moieties

“…These compounds are obtained by free radical telomerization of an acryloyl monomer such as tris(hydroxymethyl)acrylamidomethane (THAM, 1), in the presence of an alkane/ fluoroalkanethiol as a transfer reagent. Previous biological studies have shown that multifunctional molecules obtained by this method exhibit physicochemical properties and biocompatibility, making them suitable for drug delivery systems [11][12][13] .…”

Thalidomide Derivatives for the Treatment of Neuroinflammation

“…[31] A whole-body autoradiography performed on rat and mouse allowed us to confirm the ubiquitous biodistribution of THAM-derived telomers in all biological compartments except the brain. [32] Moreover, after intravenous (iv) or oral (po) administration to rat, these compounds were slowly released within 100 h, and no toxicity was observed. Finally, the anchorage of various antitumor agents, such as cytosine arabinoside (Ara-C) or 5-fluorouracil (5-Fu), to the polymeric backbone gave macromolecular prodrugs with improved bioavailability and a better therapeutic index than the parent drugs.…”

“…However, on the basis of the ability of telomers to reach the bloodstream after oral administration, [32] and considering that free thalidomide is more active when given orally, further investigation of N-(aminopropyl)amino-thalidomide telomers is necessary to specify both the best dose and mode of administration in the EAE mouse model of MS. Two factors could account for increased activity with compounds 18 and 19 after ip injection: enhanced general bioavailability due to structural modification of the parent thalidomide, and/or multiple appending of the active component on the same carrier. Considering the hydrophobic character of thalidomide, conjugation to a hydrophilic moiety might be expected to enhance activity.…”