Temperature‐Sensitive Nanocapsules for Controlled Drug Release Caused by Magnetically Triggered Structural Disruption

Abstract

Self-assembled nanocapsules containing a hydrophilic core and a crosslinked yet thermosensitive shell have been successfully prepared using poly(ethylene-oxide)-poly(propylene-oxide)-poly(ethylene-oxide) block copolymers, 4-nitrophenyl chloroformate, gelatin, and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide. The core is further rendered magnetic by incorporating iron oxide nanoparticles via internal precipitation to enable externally controlled actuation under magnetic induction. The spherical nanocapsules exhibit a hydrophilic-to-hydrophobic transition at a characteristic but tunable temperature reaching 40ºC, triggering a size contraction and shrinkage of the core. The core content experiences very little leakage at 25ºC, has a half life about 5 h at 45ºC, but bursts out within a few minutes under magnetic heating due to iron oxide coarsening and core/shell disruption. Such burst-like response may be utilized for controlled drug release as illustrated here using a model drug Vitamin B12. Nanocapsules containing magnetic iron oxide (brown precipitates) and a model drug (vitamin B12) encapsulated inside a cross-linked two-layered thermosensitive PEO-PPO-PEO shell abruptly shrink above the transition temperature (40.5 8C), which dramatically increases the drug release (compare two lower curves); they also release the drug in a burst upon remote magnetic heating (upper curve).

The design and utility of polymer-stabilized iron-oxide nanoparticles for nanomedicine applications

“…Liu et al [80] exploited the ability of IONPs to generate heat when they are subjected to a high-frequency oscillating magnetic field. In their work, IONPs were coated with a thermo-responsive anti-fouling polymer (pluronic PEG-b-PEO-b-PEG), which was cross-linked using gelatin.…”

Stimulus-responsive polymeric nanoparticles for biomedical applications

“…As a widely studied thermo-sensitive polymer, PNIPPAm is commonly used as a surface layer to encapsulate magnetic nanoparticles to prepare magnetic/thermal-responsive nanoparticles [83][84][85][86][87][88]. For example, Zhang et al fabricated magnetic cores with double bonds on the surface via the coprecipitation method.…”

Poly(ethylene glycol)‐Coated Fe3O4 Nanoparticles by UV‐Thiol‐Ene Addition of PEG Dithiol on Vinyl‐Functionalized Magnetite Surface

“…[12] The coating is a key to the final application of the nanoparticles, for example thermosensitive polymers have been used in order to combine the effects of chemiotherapy with hyperthermia. [13] It is known that the control of the size and shape in nanoparticles is one of the principal issues to improve in the chemical synthesis due to its scientific relevance and new technological applications. This topic represents an intensive area of investigation because superparamagnetism and magnetic anisotropy show a strong dependence on size, shape, and chemical composition.…”