Abstract
Colorectal cancer (CRC) is the leading cause of cancer-related complications and deaths worldwide. Treatments currently being employed have limited use due to the off-target- side effects and minimum localized retention of the medicinal agents at the tumor site. This study aims to develop and evaluate a novel Hyd-Nano drug delivery system (HNDDS) capable of effective drug delivery in CRC. The HNDDS is composed of two parts; the first comprises surface-modified nanoparticles with folic acid to specifically target tumor cells. The second part is a pH-sensitive hydrogel encapsulating the surface-modified nanoparticles and providing a pH-sensitive and controlled drug release. The HNDDS was characterized via dynamic light scattering (DLS), Fourier transformed Infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA)/diffraction scanning calorimetry (DSC) and scanning electron microscopy (SEM). In-vitro studies as sol-gel, porosity, drug loading, and entrapment efficacy etc. showed attractive results. The drug release study was conducted in simulated fluids (pH 7.4 and 1.2) using a dialysis membrane (10 kDa) and the results displayed a pH-dependent drug release in a sustained manner for up to 70 h. The pharmacokinetic profile (PK) was calculated using Kinetica® software that revealed Cmax as 621.83 + 1.94 and Tmax was increased up to 12 h, similarly the calculated MRT was 14.52 ± 0.217 h, and AUC was recorded as 7988.66 ± 221.68 ng/mL*h. The DLS results depicted the size of synthesized nanoparticles as 122 nm with PDI 0.21 and −31mV as zeta potential. Conjugation of Folic acid was estimated by UV–visible spectroscopy and the calculated amount in the sample was recorded as 15.94 ± 3.11 μg/mg. Cytotoxicity analysis for the developed HNDDS was conducted using Hela cells and IC50 values calculated for the HNDDS was 13.45 μg/mL compared to 19.12 μg/mL and 23.11 μg/mL for nanoparticles and active drug respectively. The significant swelling, release, cytocompatibility, tumor cell specific endocytosis and sustained drug delivery achieved by the HNDDS makes it an ideal candidate to be used for cargoes in CRC.
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