Kinetics and Mechanism of Synthesis of Carboxyl-Containing N-Vinyl-2-Pyrrolidone Telehelics for Pharmacological Use

Abstract

It was found that sulfanylethanoic and 3-sulfanylpropanoic acids are effective regulators of molecular weight with chain transfer constants of 0.441 and 0.317, respectively, and show an unexpected acceleration effect on the radical polymerization of N-vinyl-2-pyrrolidone, initiated by 2,2’-azobisisobutyronitrile. It was determined for the first time that the thiolate anions of mercapto acids form a high-temperature redox initiating system with 2,2’-azobisisobutyronitrile during the radical polymerization of N-vinyl-2-pyrrolidone in 1,4-dioxane. Considering the peculiarities of initiation, a kinetic model of the polymerization of N-vinyl-2-pyrrolidone is proposed, and it is shown that the theoretical orders of the reaction rate, with respect to the monomer, initiator, and chain transfer agent, are 1, 0.75, 0.25, and are close to their experimentally determined values. Carboxyl-containing techelics of N-vinyl-2-pyrrolidone were synthesized so that it can slow down the release of the anticancer drug, doxorubicin, from aqueous solutions, which can find its application in the pharmacological field.

The Synthesis and Properties of a New Carrier for Paclitaxel and Doxorubicin Based on the Amphiphilic Copolymer of N‐vinyl‐2‐pyrrolidone and Acrylic Acid

“…Non-covalent loading of doxorubicin into PVP telehelics has been recently shown to lead to highly water-soluble drug carriers. [28] At the same time, however, the release rate of doxorubicin remained high. [28] Noncovalent binding and retention of doxorubicin hydrochloride may presumably be amplified through incorporation of a small amount of the acrylic acid residues into macromolecules along with the N-vinyl-2-pyrrolidone residues.…”

Synthesis of Amphiphilic Copolymers of N-Vinyl-2-pyrrolidone and Allyl Glycidyl Ether for Co-Delivery of Doxorubicin and Paclitaxel

“…The amphiphilic low-molecular-weight poly(N-vinyl-2-pyrrolidone) proved to be effective in terms of loading with hydrophobic substances [20,21] and does not display any significant toxicity [22,23]. However, the amphiphilic N-vinyl-2-pyrrolidone homopolymer is relatively ineffective as a carrier for drugs with high solubility in water [24], which limits the possibilities of its application in combination therapy. Combination chemotherapy is one of the leading approaches in the treatment of a number of cancer types [25].…”

Amphiphilic Poly-N-vinylpyrrolidone Nanoparticles as Carriers for Nonsteroidal, Anti-Inflammatory Drugs: Pharmacokinetic, Anti-Inflammatory, and Ulcerogenic Activity Study

“…According to the method previously developed by our group, Amph-PVP polymer (PVP-OD4000) was synthesized by free-radical polymerization of N-vinylpyrrolidone monomer in the presence of azobisisobutyronitrile (AIBN) as initiator and mercaptoacetic acid (MAA) as chain-growth regulator. The following coupling reaction between carboxyl end-capped poly- N -vinylpyrrolidone with aliphatic n-octadecylamine (OD) in the presence of N, N’-dicyclohexylcarbodiimide (DCC) resulted in the desired polymer [ 24 , 25 , 26 ]. The resulting PVP-OD4000 amphiphilic polymer consists of a hydrophilic macromolecular fragment of PVP with 4000 Da molecular weight and one anchor hydrophobic n-alkyl octadecyl group.…”