Dual-Stimuli-Sensitive Smart Hydrogels Containing Magnetic Nanoparticles as Antitumor Local Drug Delivery Systems—Synthesis and Characterization

Abstract

The aim of this study was to develop an innovative, dual-stimuli-responsive smart hydrogel local drug delivery system (LDDS), potentially useful as an injectable simultaneous chemotherapy and magnetic hyperthermia (MHT) antitumor treatment device. The hydrogels were based on a biocompatible and biodegradable poly(ε-caprolactone-co-rac-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-rac-lactide) (PCLA-PEG-PCLA, PCLA) triblock copolymer, synthesized via ring-opening polymerization (ROP) in the presence of a zirconium(IV) acetylacetonate (Zr(acac)4) catalyst. The PCLA copolymers were successfully synthesized and characterized using NMR and GPC techniques. Furthermore, the gel-forming and rheological properties of the resulting hydrogels were thoroughly investigated, and the optimal synthesis conditions were determined. The coprecipitation method was applied to create magnetic iron oxide nanoparticles (MIONs) with a low diameter and a narrow size distribution. The magnetic properties of the MIONs were close to superparamagnetic upon TEM, DLS, and VSM analysis. The particle suspension placed in an alternating magnetic field (AMF) of the appropriate parameters showed a rapid increase in temperature to the values desired for hyperthermia. The MIONs/hydrogel matrices were evaluated for paclitaxel (PTX) release in vitro. The release was prolonged and well controlled, displaying close to zero-order kinetics; the drug release mechanism was found to be anomalous. Furthermore, it was found that the simulated hyperthermia conditions had no effect on the release kinetics. As a result, the synthesized smart hydrogels were discovered to be a promising antitumor LDDS, allowing simultaneous chemotherapy and hyperthermia treatment.

Extracellular Vesicles and Hydrogels: An Innovative Approach to Tissue Regeneration

“…By subjecting these hydrogels to a magnetic field, it is possible to alter their shape, resulting in the formation of large pores and enabling rapid deformation without causing any physical harm. This process greatly aids in the quick release of enclosed particles . Ultrasound, a different external force, has the ability to temporarily disturb the structure of the hydrogel.…”

“…This process greatly aids in the quick release of enclosed particles. 239 Ultrasound, a different external force, has the ability to temporarily disturb the structure of the hydrogel. This disturbance not only initiates the liberation of hydrogel components such as nanobubbles, liposomes, and NPs but also amplifies the infiltration and absorption of medications within tissues.…”

The Method of Direct and Reverse Phase Portraits as a Tool for Systematizing the Results of Studies of Phase Transitions in Solutions of Thermosensitive Polymers

“…Sobczak et al’s study on the development of injectable, thermosensitive hydrogel drug delivery systems for the release of 5-fluorouracil and paclitaxel. Biodegradable triblock copolymers were synthesized via ring-opening polymerization of epsilon-caprolactone or rac-lactide with PEG and zirconium(IV) acetylacetonate (Zr(acac)4) as co-initiator and catalyst [ 58 , 59 , 60 ].…”