Reduction-Responsive Molecularly Imprinted Poly(2-isopropenyl-2-oxazoline) for Controlled Release of Anticancer Agents

Abstract

Trigger-responsive materials are capable of controlled drug release in the presence of a specific trigger. Reduction induced drug release is especially interesting as the reductive stress is higher inside cells than in the bloodstream, providing a conceptual controlled release mechanism after cellular uptake. In this work, we report the synthesis of 5-fluorouracil (5-FU) molecularly imprinted polymers (MIPs) based on poly(2-isopropenyl-2-oxazoline) (PiPOx) using 3,3′-dithiodipropionic acid (DTDPA) as a reduction-responsive functional cross-linker. The disulfide bond of DTDPA can be cleaved by the addition of tris(2-carboxyethyl)phosphine (TCEP), leading to a reduction-induced 5-FU release. Adsorption isotherms and kinetics for 5-FU indicate that the adsorption kinetics process for imprinted and non-imprinted adsorbents follows two different kinetic models, thus suggesting that different mechanisms are responsible for adsorption. The release kinetics revealed that the addition of TCEP significantly influenced the release of 5-FU from PiPOx-MIP, whereas for non-imprinted PiPOx, no statistically relevant differences were observed. This work provides a conceptual basis for reduction-induced 5-FU release from molecularly imprinted PiPOx, which in future work may be further developed into MIP nanoparticles for the controlled release of therapeutic agents.

Advances in Molecularly Imprinted Polymers as Drug Delivery Systems

“…Recently, Cegłowski et al studied a reduction-responsive MIP of poly(2-isopropenyl-2oxazoline) (PiPOx), prepared by ring-opening polymerization of iPOx, for the controlled release of 5-FU [47]. The cross-linker 3,3-dithiodipropionic acid (DTDPA) contains disulphide bonds that attract reduction-sensitive materials, thereby enabling a reduction-triggered release mechanism.…”

“…These monomers are considered to have acceptable toxicity and excellent biocompatibility [78,120,127], though their long-term toxicity and metabolic pathways have not been evaluated in depth. Besides, additional materials such as POSS [45,104], β-CD [45], CS [89], silicon [91,139] and stimuli-sensitive materials [47,70,124] have been used to modify MIPs to improve performance parameters such as drug release behavior, biodegradability and biocompatibility [67]. As can be seen, in comparison to the conventional active targeting polymeric DDSs, double-imprinted MIP NPs offer a benefit by significantly reducing aspecific drug release and improving therapeutic effects.…”

Isotherm and Electrochemical Properties of Atrazine Sensing Using PVC/MIP: Effect of Porogenic Solvent Concentration Ratio

“…Thus, a pseudo functional material for specific recognition of target compounds by imprinting the functional groups and conformation of template molecules, known as Molecular Imprinted Polymer (MIP), has received outstanding research and application in various fields such as separation process [ 7 ], pharmaceuticals [ 8 ], sensors [ 9 , 10 , 11 ], and drug delivery [ 12 , 13 , 14 , 15 , 16 ]. This is due to its characteristics; MIPs are robust, stable, relatively inexpensive, resistant to a wide range of pH, humidity, and temperature and can be synthesized for analytes for which no natural antibody exists.…”

Starch‐Based Membranes for Controlled Release of 5‐Fluorouracil In Vitro

“…Lurciuc-Tincu et al [18] loaded 5-FU on a biocompatible poly(2-vinyl pyridine)β-poly(ethylene oxide) nano micelles. Cegłowski et al [19] synthesized 5-FU molecularly imprinted polymers (MIPs) based on poly(2-isopropenyl-2-oxazoline). Farboudi et al [20] synthesized magnetic gold-coated poly(ε-caprolactonediol) based polyurethane/poly(N-isopropyl acrylamide)-grafted-chitosan core-shell nano fibers for the controlled release of 5-FU.…”