Magnetic and Thermal-sensitive Poly(N-isopropylacrylamide)-based Microgels for Magnetically Triggered Controlled Release

Summary

This manuscript describes the preparation of magnetic and thermal-sensitive microgels via a temperature-induced emulsion without chemical reaction. These sensitive microgels were synthesized by mixing poly(N-isopropylacrylamide) (PNIPAAm), polyethylenimine (PEI) and Fe₃O₄-NH₂ nanoparticles for the potential use in magnetically and thermally triggered drug-release.

Abstract

Magnetically and thermally sensitive poly(N-isopropylacrylamide) (PNIPAAm)/Fe₃O₄-NH₂ microgels with the encapsulated anti-cancer drug curcumin (Cur) were designed and fabricated for magnetically triggered release. PNIPAAm-based magnetic microgels with a spherical structure were produced via a temperature-induced emulsion followed with physical-crosslinking by mixing PNIPAAm, polyethylenimine (PEI), and Fe₃O₄-NH₂ magnetic nanoparticles. Because of their dispersity, the Fe₃O₄-NH₂ nanoparticles were embedded inside the polymer matrix. The amine groups exposed on the Fe₃O₄-NH₂ and PEI surface supported the spherical structure by physically crosslinking with the amide groups of the PNIPAAm. The hydrophobic anti-cancer drug curcumin can be dispersed in water after encapsulation into the microgels. The microgels were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), and UV-Vis spectral analysis. Furthermore, magnetically triggered release was studied under an external high frequency magnetic field (HFMF). A significant "burst release" of curcumin was observed after applying the HFMF to the microgels due to the magnetic inductive heating (hyperthermia) effect. This manuscript describes the magnetically triggered controlled release of Cur-PNIPAAm/Fe₃O₄-NH₂ encapsulated curcumin, which can be potentially applied for tumor therapy.

Introduction

Hydrogels are three-dimensionally (3D) polymeric networks which cannot dissolve but can swell in aqueous solutions¹. The polymeric networks have hydrophilic domains (which can be hydrated to provide the hydrogel structure), and a cross-linked conformation (which can prevent the collapse of the network). Various methods have been investigated for preparation of hydrogels, such as emulsion polymerization, anionic copolymerization, crosslinking of neighboring polymer chains, and inverse micro-emulsion polymerization². Physical and chemical cross-linking are introduced through these methods to obtain structurally stable hydr....

Protocol

1. Synthesis of Surface-modified, Water-dispersible, Magnetic Nanoparticles, Fe₃O₄ and Fe3O4-NH₂

1. Add 14.02 g of FeCl₃, 8.6 g of FeCl₂·4H₂O and 250 mL water to a 500-mL beaker.
2. Connect the rotor and controller to set up mechanic stirring. Mix the solution at 300 rpm for 30 min at room temperature (RT).
3. Add 25 mL of ammonium hydroxide (33%) into the solution at RT and keep stirring (300 rpm) for 30 min. Keep the beaker open.
   CAUTION: Ammonium hydroxide may cause nose irritation if inhaled. This step must be performed inside an appropriate fume hood.
4. To collec....

Results

The schematic for synthesis of PNIPAAm/PEI/Fe₃O₄-NH₂ microgels is shown in Figure 1. TGA was applied to estimate the relative composition of the organic compound against the whole microgel. Since only the organic compound PNIPAAm could be burned, the relative composition of PNIPAAm and Fe₃O₄ (or Fe₃O₄-NH₂) was determined and is shown in Table 1. Why do PNI.......

Discussion

The most important steps of the preparation are in protocol section 2, for the synthesis of the magnetic microgels by thermo-induced emulsion. As shown in Figure 2 (TEM images), the spherical structure of microgels could be maintained at RT (lower than the LCST) due to the physical crosslinking resulting from the strong H-bonding between PNIPAAm (amide groups), PEI (amine groups) and Fe₃O₄-NH₂ (amine groups). Based on the comparison in Fi.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Poly(N-isopropylacrylamide)	Polyscience, Inc	21458-10	Mw ~40,000
(3-aminopropyl)trimethoxysilane	Sigma-Aldrich	440140	> 99 %
Iron(II) chloride tetrahydrate	Sigma-Aldrich	44939	99%
Iron(III) chloride	Sigma-Aldrich	157740	97%
Curcumin	Sigma-Aldrich	00280590
Ammonia hydroxide	Fisher Chemical	A/3240/PB15	35%
Phosphate Buffered Saline	Sigma-Aldrich	806552	pH 7.4, liquid, sterile-filtered
Polyethylenimine (PEI)	Sigma-Aldrich	P3143	50 % (w/v) in water
High-frequency magnetic field (HFMF)	Lantech Industrial Co., Ltd.,Taiwan	LT-15-80	15 kV, 50–100 kHz
Ultraviolet-Visible Spectrophotometry	Thermo Scientific Co.	Genesys
Transmission electron microscopy (TEM)	JEM-2100	JEOL
Fourier transform infrared spectroscopy (FTIR)	PerkinElmer	Spectrum 100
Thermogravimetric analyzer	PerkinElmer	Pyris 1
Ultrasonic cell disruptor	Hielscher Ultrasonics	UP50H