Enhancement of Drug Release Efficiency Using Magnetic Nano composite

Abstract

The current study presents a bimodal therapeutic platform based on superparamagnetic iron oxide nanoparticles (SPIONs), poly(N-isopropylacylamide) (PNIPAAm), and a Poly (ADP-ribose) polymerase-1(PARP-1) inhibitor; 5-aminoisoquinoline (5-AIQ). The magnetic thermoresponsive nanocomposite (MTN) was synthesized in a core-shell morphology by in situ free-radical polymerization of N-isopropylacrylamide in the presence of the ferrofluid of 11 nm SPIONs cores. The composite was allowed to swell in various concentrations of the drug (5-AIQ) forming drug-loaded magnetic thermoresponsive nanocomposite (MTN.5-AIQ). Bimodal therapy implies that the presented drug loaded core-shell structure (MTN.5-AIQ) has the capability of elevating the tumor tissue temperature (hyperthermia) through the superparamagnetic iron oxide core and simultaneously releasing a drug 5-AIQ.The capability of Superparamagnetic iron oxide nanoparticles (SPIONs) as successful hyperthermia agents was proved by measuring the specific absorption rate of SPIONs by an induction heater. Poly(N-isopropylacrylamide (PNIPAAm) is the most commonly used thermoresponsive polymer that responds to a change in temperature by changing its solubility and exhibiting sol-gel transition. SPIONs and PNIPAAm constitute the magnetic thermoresponsive nanocomposite (MTN). To the author's knowledge, the combination of magnetic nano-composites with PARP-1 modifying agents has not been previously investigated. Structural characterization of the formed composite was studied via various experimental tools; X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, energy dispersive X-ray (EDX) spectroscopy, and thermal gravimetric analysis (TGA). The vibrating sample magnetometer (VSM) was used to study the magnetic properties of the composite. Specific absorption rates (SARs) of SPIONs were measured by an induction heater. The lower critical solution temperatures (LCSTs) of PNIPAAm, MTN and MTN.5-AIQ were determined by the differential scanning calorimetry (DSC). The cloud point temperature of PNIPAAm was measured by a turbidimeter and UV-visible spectroscopy. The results confirmed the formation of (MTN) with excellent potential for hyperthermia. A high drug loading efficiency (85.72%) was obtained with convenient temperature-dependent drug release kinetics. In vivo and in vitro studies were used to assess biocompatibility and cytotoxic efficacy respectively. MTN.5-AIQ administration (to normal mice) resulted in normal hepatic and renal function, as well as a lower toxic effect on normal tissue. In addition, the drug-loaded composite effectively inhibited Caco-2 cells viability upon incubation. Based on the obtained results, the proposed therapeutic platform can be considered as a novel, promising candidate for bimodal therapy of colorectal adenocarcinoma (CRC) exhibiting a PARP-1 overexpression.