PEGylated green halloysite/spinel ferrite nanocomposites for pH sensitive delivery of dexamethasone: A potential pulmonary drug delivery treatment option for COVID-19.

Dexamethasone (Dex) is used in drug regimen for treatment of Coronavirus disease (COVID-19). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) fusion and entry into the cell occurs at pH 5.5. In our present study, we have identified a green, cheap clay based halloysite (Hal) nanoformulation with release capability of Dex at such interactive pH condition. 30%ZnFe ₂ O ₄ /Hal and 30%NiFe ₂ O ₄ /Hal were prepared by one-pot synthesis technique. Dex (5% wt/wt) was functionalized over both nanocomposites. Finally, polyethylene glycol (PEG) was coated over ZnFe ₂ O ₄ /Hal/Dex and NiFe ₂ O ₄ /Hal/Dex nanocomposite using lyophilization technique (0.08 μl/mg of nanocarrier). The release ability of Dex was studied under pulmonary infection and normal pH conditions (pH = 5.6 and 7.4). The characterization study using X-ray diffraction (XRD) and UV-visible diffuse reflectance (DRS) spectra confirmed the presence of spinel ferrites over Hal. Nitrogen adsorption isotherm showed the surface area of ZnFe ₂ O ₄ /Hal (75 m ² /g), pore volume (0.27 cm ³ /g) with average pore size (14.5 nm). Scanning electron microscope/Energy dispersive spectroscopy (SEM-EDS) and Transmission electron microscopy analysis revealed a textural change in halloysite tubular type indicating drug adsorption and PEG adhesion. DRS spectra indicated an intergrowth of zinc ferrite nanoparticles on the halloysite nanotubes. Interestingly, ZnFe ₂ O ₄ /Hal/Dex/PEG exhibited a high Dex release ability (17.5%, 168 h) at pH = 5.6 relevant to SARS-CoV-2 fusion entry into the cell pH condition of 5.5. Comparatively, the nanocomposite showed a less Dex release (<5%) release for 168 h at neutral pH = 7.4. The drug release kinetics were studied and the obtained data were fitted for the release constant and release exponent, using the Korsmeyer-Peppas model. To test the compatibility of our nanocomposites, we performed the cell viability assay (MTT) using HEK293 cells. Our results showed that at 0.3 mg/ml, Dex-loaded nanocomposite had a statistically significant improvement in cell viability compared to Dex alone. These results suggest that our nanocomposite has prevented the toxic effect of Dex and has huge potential to act as pulmonary drug delivery system for targeted lung infection therapeutics.
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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