Hybrid protein-polymer nanoparticles loaded with cisplatin: synthesis and characterization

Abstract

Nowadays, many research related tovhybrid materials and the advances in Reversible-Deactivation Radical Polymerization (RDRP) techniques have enabled the development of responsive materials. These compounds respond to specific stimuli and have been integrating many research projects involving different drug delivery systems. In particular, hybrid conjugates based on protein−polymer have been integrating different formulations already approved by the Food and Drug Administration. In general, protein-polymer conjugates can increase the drug plasmatic half-life, altering the drug biodistribution profile and opening the possibility to reduce the dose administrated, which is a relevant advantage for patients. In this work, poly (N-vinylcaprolactam) (PNVCL) and poly (2-dimethylamino-ethyl methacrylate) (PDMAEMA) polymers were grafted to the surface of a protein model, the bovine serum albumin (BSA), by grafting-from approach, using the Atom Transfer Radical Polymerization (ATRP) technique. Firstly, a macroinitiator (BSA-MI) was successfully obtained and characterized by Sodium dodecyl sulfate polyacrylamide gel electrophoresis and Matrix-Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry by modifying lysine groups present in the BSA. Then, the BSA-PNVCLco-PDMAEMA hybrid was synthesized using BSA-MI as an initiator. The conjugate production was evaluated, revealing significant changes in the nanoparticles’ molecular mass and zeta potential . Additionally, it is demonstrated that altering the monomers' ratio can further adjust the lower critical solution temperature (LCST) of the protein-polymer conjugates. The results indicate the obtaining of a BSA-PNVCL-coPDMAEMA able to encapsulate approximately 1.9 mg of cisplatin for each 1 mg of the hybrid, making this conjugate a very promising hybrid material with desirable properties for a possible application in smart drug delivery systems.