Nanoaggregates of Biphilic Carboxyl-Containing Copolymers as Carriers for Ionically Bound Doxorubicin

Abstract

Application of nanocarriers for drug delivery brings numerous advantages, allowing both minimization of side effects common in systemic drug delivery and improvement in targeting, which has made it the focal point of nanoscience for a number of years. While most of the studies are focused on encapsulation of hydrophobic drugs, delivery of hydrophilic compounds is typically performed via covalent attachment, which often requires chemical modification of the drug and limits the release kinetics. In this paper, we report synthesis of biphilic copolymers of various compositions capable of self-assembly in water with the formation of nanoparticles and suitable for ionic binding of the common anticancer drug doxorubicin. The copolymers are synthesized by radical copolymerization of N-vinyl-2-pyrrolidone and acrylic acid using n-octadecyl-mercaptan as a chain transfer agent. With an increase of the carboxyl group’s share in the chain, the role of the electrostatic stabilization factor of the nanoparticles increased as well as the ability of doxorubicin as an ion binder. A mathematical description of the kinetics of doxorubicin binding and release is given and thermodynamic functions for the equilibrium ionic binding of doxorubicin are calculated.

Intrinsically Disordered Synthetic Polymers in Biomedical Applications

“…Intrinsically disordered proteins (IDPs) play a number of unique and important roles in various biological processes due to their inherent flexibility and ability to undergo con-formational changes in response to environmental cues ( Table 1 ) [ 23 , 24 , 25 ]. These properties also make IDPs well suited for a variety of biomedical applications [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ], including: (i) Self-assembly: IDPs can self-assemble into a variety of nanostructures, such as micelles, nanoparticles, and hydrogels, which can be used for drug delivery; (ii) Controlled release: the ability of IDPs to undergo conformational changes can also allow for the controlled release of drugs; (iii) Targeting: IDPs can be designed to recognize specific biological targets, such as cells and proteins, through binding interactions.…”

“…Overall, the use of polymers in drug delivery offers a wide range of benefits and has led to the development of new and innovative drug delivery systems that are more effective, targeted, and patient-friendly. Artyukhov et al synthesized biophilic copolymers of various compounds that can self-assemble in water with the formation of polymeric nanoparticles and are suitable for ionic binding of the common anticancer drug doxorubicin for drug delivery application [ 25 ]. Accordingly, the copolymers were synthesized by the radical copolymerization of N-vinyl-2-pyrrolidone and acrylic acid using n-octadecyl-mercaptan as the chain transfer agent.…”

Toxicity Evaluation and Controlled-Release of Curcumin-Loaded Amphiphilic Poly-N-vinylpyrrolidone Nanoparticles: In Vitro and In Vivo Models

“…Parameters such as the copolymer molecular weight, morphology and size of the micelles are easily controlled during the synthesis process. They can capture various therapeutic agents, such as non-steroidal anti-inflammatory drugs [ 19 , 20 , 21 ], antitumor drugs [ 22 ], antifungal antibiotics [ 23 ], cytokines [ 24 , 25 ] and plasmid DNA [ 26 ] in micelles. Depending on the average hydrodynamic radius, nanoparticles can be absorbed by cell cultures through various mechanisms, including endocytosis and membrane fusion, which allows selective delivery of the active substance to both the cell’s endosomes and its nucleus [ 27 ].…”

Promising Gene Delivery Properties of Polycations Based on 2-(N,N-dimethylamino)ethyl Methacrylate and Polyethylene Glycol Monomethyl Ether Methacrylate Copolymers

“…It should be noted that cationic polyelectrolytes with a high charge density also have high cytotoxicity, which can be reduced by introducing polyethylene glycol (polyethylene oxide—PEO), which has good water solubility and biocompatibility, into their composition. On the other hand, the introduction of hydrophilic PEO fragments into DNA carrier copolymers can promote the development of adverse immune responses for a small number of patients capable of producing PEO—directed immunoglobulins [ 46 ]. However, for the vast majority of patients, pegylated carriers are non-immunogenic and are gold standards for the delivery of pharmacologically active substances.…”