Preparation, Cellular Uptake, and Cytotoxic Evaluation of Remdesivir-Hydroxypropyl-β-Cyclodextrin Inclusion Complex.
Saraswati Ramadhani Priyono
, Sutriyo*and Ratika RahmasariFaculty of Pharmacy, Universitas Indonesia, Depok, Indonesia, 16424.
Corresponding Author E-mail: sutriyo@farmasi.ui.ac.id
Abstract: Covid-19 was mainly treated by a broad-spectrum antiviral called Remdesivir. A truncated cone molecular structure of Hydroxypropyl-β-cyclodextrin can enhance the solubility and cellular uptake of the poorly soluble drug's through biological membranes. This study aimed to synthesize, characterize, observe cellular uptake and evaluate the cytotoxicity of remdesivir-hydroxypropyl-β-cyclodextrin (RDV-HPβCD) inclusion complex. The RDV-HPβCD inclusion complex was synthesized by the solvent evaporation method. Furthermore, the inclusion complex characteristic was evaluated by ultraviolet-visible (UV-Vis) spectrophotometry; particle size analyzer (PSA); Fourier infrared spectrophotometry (FTIR); X-ray diffraction (XRD); and differential scanning calorimetry (DSC). Further, fluorescence microscopy was used to evaluate the cellular uptake and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used in the cytotoxicity study. In the UV-Vis spectrum, both the inclusion complex and pure remdesivir showed a maximum peak at 246 nm. The inclusion complex has a particle size of 1697 ± 738.02 nm with -22.4 ± 1.58 mV of zeta potential. Shifted FTIR spectrum, broad XRD peak, and broad DSC thermogram peak at 72.93 °C indicated the successful formation of the RDV-HPβCD inclusion complex. Furthermore, cellular uptake observation of RDV-HPβCD inclusion complex conjugated to FITC showed better intensity inside the Vero cell than pure remdesivir conjugated to FITC. Further, Inclusion complex showed higher cell viability than pure remdesivir at a certain concentration.
Keywords: Cellular Uptake; Cytotoxicity; Hydroxypropyl-β-Cyclodextrin; Inclusion Complex; MTT assay; Remdesivir Back to TOC