Polymeric prodrugs, 3. Synthesis, elimination, and whole‐body distribution of ¹⁴C‐labelled drug carrier

Abstract

An alternating copolymer of 1-vinyl-2-pyrrolidone and maleic anhydrig, I4C-labelled at the chain end, was synthetized with a mass-average relative molecular mass M, = 8000. Elimination kinetics and whole-body distribution of the copolymer in its monosodium salt form were studied in mice. Elimination of the copolymer was found to be fairly rapid and practically complete, i. e. 86,7% of it was excreted after 24 h and 95% after 56 h. Specific accumulation of the copolymer was observed in bone tissue and lacrimal gland. No appreciable accumulation occurred in the nervous system, spleen, and bone marrow. The results of elimination kinetics and the autoradiographic whole-body distribution study were in fairly good correlation.

New ester and lactone end-functionalized N-vinyl-2-pyrrolidinone oligomers

“…However, in contrast to proteins, PVP is physiologically inactive which has led to its use as a blood plasma substitute or blood volume expander 5) , although these applications are now very much restricted since it is not metabolized or in any way degraded in the body. Moreover, PVP was the first synthetic polymer to be used for the modification of therapeutically useful enzymes 6) and it has been proposed as a soluble drug carrier 7,8) .…”

Poly(N‐vinylpyrrolidone)–polydimethylsiloxane amphiphilic ABA triblock copolymers

“…PNVP can be found in personal care products such as shampoos and cosmetics, foods, textiles, pharmaceuticals drugs, and many more diverse applications. PNVP is also been proposed for the modification of therapeutically useful enzymes and as a soluble drug carrier …”

Grafting of ω-Functionalized PVP Oligomers onto Dextran: A Novel Route to Biodegradable and Biocompatible Polymers

“…PVP has also been proposed for the modification of therapeutically useful enzymes [21] and as a soluble drug carrier. [22,23] Communication: x-Hydroxy-functionalized oligo(Nvinyl-2-pyrrolidinone) (PVPOH) was prepared by chaintransfer radical polymerization in the presence of 2-isopropoxyethanol as the chain-transfer agent, and grafted onto dextran. Two PVP-Dex graft copolymers were obtained starting from different PVPOH/dextran weight ratios in the feed, namely 2 : 1 and 5 : 1.…”

“…Finally, they will undergo kidney filtration after degradation on condition that the molecular weight of the grafted VP oligomers is well below the threshold required for glomerular filtration, which for PVP was identified to be 40 000. [23] The chemical modification of dextran via the grafting of PVP segments leads to a relevant transformation of its overall solution properties, regarding both hydrophobic/ hydrophilic balance and solution dimensions in biological aqueous media. Moreover, the physiological inertness of PVP might improve the overall biological performance of dextran, which has sometimes been imputed for severe allergic reactions.…”