Poly(oligoethylene glycol methacrylate) Star‐Shaped Copolymers with Hydroxypropyl Methacrylate Cores

Abstract

Star-shaped copolymers with crosslinked hyperbranched cores, varying in both number and length of the arms, are prepared by the reversible addition-fragmentation chain transfer (RAFT) polymerization technique. Star synthesis is conducted via a simple, "core-first" method. Hydroxypropyl methacrylate monomer is used for the formation of the hyperbranched/crosslinked core, with ethylene glycol dimethacrylate used as a bifunctional monomer in the role of the cross-linker. Two different cross-linker/chain transfer agent ratios are chosen to manipulate the number of the arms in the final star nanostructure. Oligoethylene glycol methacrylate (OEGMA 500 ) is used as a biocompatible and hydrophilic component for the creation and extension of the arms. Arm length is controlled by the amount of OEGMA monomer used in the second polymerization step. Molecular characterization of the four synthesized stars is achieved via size exclusion chromatography and nuclear magnetic resonance, which provides information regarding the molar mass, dispersity, and composition of each star-shaped copolymer. Dynamic light scattering (DLS) studies of copolymers in N,N-dimethyl formamide solutions provide sizes of individual copolymer molecules in the size range of 8-20 nm. Aqueous dispersions of copolymers are investigated by DLS, cryogenic transmission electron microscopy, and atomic force microscopy, which show the formation of spherical aggregates with diameters of 60-350 nm, dependent on the arm number and length of star copolymers. The obtained sizes and size distributions, along with the hydroxyl-group-bearing cores, indicate that the star copolymer can be used as potential nanocarriers for drugs or bioimaging agents.

Betulin‐containing bioactive amphiphilic copolymers: Synthesis, characterization and self‐assembly

“…Our results and literature data indicate that micellar polymeric systems based on oligo(ethylene glycol) methacrylates containing BeMA as a comonomer are promising as biocompatible polymeric carriers for targeted drug delivery. For example, thermoresponsive copolymers of MOEGMA with hydrophobic comonomers were shown to efficiently encapsulate hydrophobic drugs, in particular, curcumin 43–46 . It was shown 47 that drug delivery systems using oligoethylene glycol conjugates of betulin derivatives increase drug potential by improving solubility and specificity and can help in overcoming chemoresistance in pancreatic cancer.…”

“…The copolymers obtained in this work are characterized by: The ability to form unimolecular micelles resistant to dissociation. The main advantage of unimolecular micelles is their stability when diluted, which in other cases can only be achieved using crosslinking agents 46 ; Intrinsic biological (antioxidant) activity due to the presence of betulin in a macromolecule; High solubility. It is known that betulin is almost insoluble in water (<8·10 −5 mg/mL) 51 .…”

“…For example, thermoresponsive copolymers of MOEGMA with hydrophobic comonomers were shown to efficiently encapsulate hydrophobic drugs, in particular, curcumin. [43][44][45][46] It was shown 47 that drug delivery systems using oligoethylene glycol conjugates of betulin derivatives increase drug potential by improving solubility and specificity and can help in overcoming chemoresistance in pancreatic cancer. The more pronounced antitumor activity of conjugates with PEG, compared to the pure drug, is associated with a prolonged residence of the drug in the tumor area due to the EPR effect.…”

“…The main advantage of unimolecular micelles is their stability when diluted, which in other cases can only be achieved using crosslinking agents 46 ;…”

Hydroxypropyl methacrylate stars as versatile carriers of therapeutic agents

“…Depending on side group length and its end group, the synthesized poly(oligoethylene glycol methacrylate) (POEGMA) polymers can be either water-soluble, thermoresponsive or insoluble in water. 10,[45][46][47][48][49] In this study, previously synthesized star copolymers, containing a crosslinked poly(hydroxy propyl methacrylate-co-ethylene glycol dimethacrylate) (P(HPMA-co-EGDMA)) copolymer core and POEGMA arms of varying numbers and lengths, 50 were utilized for investigating the encapsulation of rhodamine B, resveratrol, or curcumin. The objective of this study is to utilize these three agents, characterized by different degrees of hydrophilicity, to investigate their potential interactions with OH groups of poly(hydroxy propyl methacrylate) (PHPMA) core, to study the stability of stars carriers and evaluate their potential as stable nanoplatforms for a wide range of nanomedical applications.…”