Alternating Magnetic Field-Responsive Hybrid Gelatin Microgels for Controlled Drug Release

Summary

We present a facile method to fabricate a biodegradable gelatin-based drug release platform that is magneto-thermally responsive. This was achieved by incorporating superparamagnetic iron oxide nanoparticles and poly(N-isopropylacrylamide-co-acrylamide) within a spherical gelatin micro-network crosslinked by genipin, in conjunction with an alternating magnetic field application system.

Abstract

Magnetically-responsive nano/micro-engineered biomaterials that enable a tightly controlled, on-demand drug delivery have been developed as new types of smart soft devices for biomedical applications. Although a number of magnetically-responsive drug delivery systems have demonstrated efficacies through either in vitro proof of concept studies or in vivo preclinical applications, their use in clinical settings is still limited by their insufficient biocompatibility or biodegradability. Additionally, many of the existing platforms rely on sophisticated techniques for their fabrications. We recently demonstrated the fabrication of biodegradable, gelatin-based thermo-responsive microgel by physically entrapping poly(N-isopropylacrylamide-co-acrylamide) chains as a minor component within a three-dimensional gelatin network. In this study, we present a facile method to fabricate a biodegradable drug release platform that enables a magneto-thermally triggered drug release. This was achieved by incorporating superparamagnetic iron oxide nanoparticles and thermo-responsive polymers within gelatin-based colloidal microgels, in conjunction with an alternating magnetic field application system.

Introduction

Stimuli-responsive drug delivery systems that enable a tightly controlled drug delivery in response to either endogenous or exogenous stimuli (e.g., temperature or pH) have been extensively investigated as new types of smart soft devices for drug delivery. Microscale hydrogels have been widely employed as a drug delivery platform in that they confer controllable and sustainable drug release profiles as well as tunable chemical and mechanical properties^1-3. In particular, the colloidal microgels exhibit many advantages as a vehicle for drug delivery due to their rapid responsiveness to external stimuli and suitable injectability to local tissue in a....

Protocol

Note: The overall process of fabricating magnetic field-responsive gelatin microgels is illustrated in Figure 1A.

1. Preparing Solutions and Suspensions

1. Prepare a crosslinker genipin (1% w/v) solution by dissolving 20 mg of genipin in 2 ml of phosphate buffered saline (1x PBS; pH 7.4). Vortex the solution and place in a 50 ^oC water bath for 2 hr to completely dissolve the solution.
2. Prepare a surfactant solution by dissolving 20 mg of poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) (M_w = 2,900 Da; referred to as L64) in 200 ml of PBS to be at the concentration of....

Results

When the protocol is performed correctly, the fabricated microgels should exhibit a well-characterized spherical morphology and colloidal dispersibility with diameters in the range between 5 μm to 20 μm (Figure 1B and C). Either fluorescent MNPs or fluorescent BSA can be used to confirm whether MNPs or drugs (BSA in this study) are properly encapsulated within the microgel (Figure 1D). The fabricated microgels can be stable and stored at 4 ^oC f.......

Discussion

The technology described here demonstrates a proof of concept on the use of nanoparticle-microgel hybrids for magneto-thermally triggered drug release. This was achieved by physically entrapping MNPs and p(NIPAM-co-AAm) chains within a microscale three-dimensional gelatin network crosslinked by genipin. The magnetic field-responsive platform was sufficient to generate heat within the microgel in response to a remotely applied AMF, which in turn triggered the release of a model drug, BSA.

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Gelatin	Sigma-Aldrich, MO, USA	G2500	Gelatin type A, porcine skin
poly(N-isopropylacrylamide-co-acrylamide)	Sigma-Aldrich, MO, USA	738727	MW = 20,000, LCST = 34 - 38 °C
Silicone oil	Sigma-Aldrich, MO, USA	378372	Viscosity 350 cSt
Pluoronic L64	Sigma-Aldrich, MO, USA	435449	poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol)
genipin	TimTec LLC, DE, USA	ST080860	MW = 226.23
Magnetic nanoparticles (MNPs)	Micromod Inc, Germany	79-00-102	nanomag-D-spio, 100 nm
TR-BSA	Life Technologies, NY USA	A23017	Albumin from Bovine Serum (BSA), Texas Red conjugate