Antiepileptic drug-loaded and multifunctional iron oxide@silica@gelatin nanoparticles for acid-triggered drug delivery

Abstract

The current study developed an innovative design for the production of smart multifunctional core-double shell superparamagnetic nanoparticles (NPs) with a focus on the development of a pH-responsive drug delivery system tailored for the controlled release of Phenytoin, accompanied by real-time monitoring capabilities. In this regard, the ultra-small superparamagnetic iron oxide@silica NPs (IO@Si MNPs) were synthesized and then coated with a layer of gelatin containing Phenytoin as an antiepileptic drug. The precise saturation magnetization value for the resultant NPs was established at 26 emu g^-1. The polymeric shell showed a pH-sensitive behavior with the capacity to regulate the release of encapsulated drug under neutral pH conditions, simultaneously, releasing more amount of the drug in a simulated tumorous-epileptic acidic condition. The NPs showed an average size of 41.04 nm, which is in the desired size range facilitating entry through the blood-brain barrier. The values of drug loading and encapsulation efficiency were determined to be 2.01 and 10.05%, respectively. Moreover, kinetic studies revealed a Fickian diffusion process of Phenytoin release, and diffusional exponent values based on the Korsmeyer-Peppas equation were achieved at pH 7.4 and pH 6.3. The synthesized NPs did not show any cytotoxicity. Consequently, this new design offers a faster release of PHT at the site of a tumor in response to a change in pH, which is essential to prevent epileptic attacks.

Keywords: Antiepileptic drug; Drug delivery; Gelatin; Phenytoin; Silica; Superparamagnetic nanoparticles; pH-sensitivity.

Figure 1

Timeline of milestones in PHT-loaded NPs for epileptic seizures over the last ten years, based on the results from references^–,–.

Figure 2

Representative illustration of the core-double shell arrangement of PHT-loaded IO@Si@Gel MNPs.

Figure 3

The physicochemical properties; (a) The FTIR spectra of IO MNPs, IO@Si MNPs, and IO@Si@Gel MNPs; (b) XRD pattern of IO MNPs, and IO@ Si MNPs; (c) DSC thermograms of IO MNPs, IO@Si MNPs, and IO@Si@Gel MNPs; d) VSM curve of IO MNPs and IO@Si@Gel MNPs.

Figure 4

The SEM images of (a) IO MNPs, (b) IO@Si MNPs, and (c) PHT-loaded IO@Si@Gel MNP; TEM images of (d) IO MNPs and (e) PHT-loaded IO@Si@Gel MNP; size distributions of (f) IO MNPs and (g) PHT-loaded IO@Si@Gel MNP.

Figure 5

EDX results of (a) IO MNPs, (b) IO@Si MNPs, and (c) IO@Si@Gel MNPs.

Figure 6

In vitro studies; (a) Standard calibration curve of PHT; (b) The DR profile at different pH from PHT-loaded IO@Si@Gel MNPs; (c) MTT assay of the IO@Si@Gel MNPs treated on L-929 cells.