RESUMEN
This study aimed to assess and compare diverse formulations of ivermectin-loaded liposomes, employing lipid film hydration and ethanol injection methods. Three lipids (DOPC, SPC, and DSPC) were used in predetermined molar ratios. A total of 18 formulations were created, and a factorial design determined the optimal formulation based on particle size, polydispersity index (PDI), zeta potential, and encapsulation efficiency. The average mean particle size, PDI and zeta potential of the selected formulations (F1, F2, F7, F9, and F11) was, respectively, 196.40 ± 44.60 nm, 0.39 ± 0.09, and -40.24 ± 9.17. The encapsulation efficiency exceeded 80%, with a mean loading capacity of 4.00 ± 1.70%. In vitro studies included transmission electron microscopy, Fourier transform infrared spectroscopy, drug release, and antiviral activity assessments against SARS-CoV-2. The liposomal formulations demonstrated superior antiviral activity compared to free ivermectin, as indicated by lower IC50 values. The results of this study emphasize the effectiveness of ivermectin-loaded liposomes in inhibiting viral activity, highlighting their potential as promising candidates for antiviral therapy. The findings suggest that the strategic use of liposomes as drug carriers can significantly modulate and improve the antiviral properties of ivermectin, offering a novel approach to harnessing its full therapeutic potential. Collectively, these results provide a robust foundation for further exploration of ivermectin as a viral protection tool and optimization of its delivery mechanisms.
Asunto(s)
Antivirales , Portadores de Fármacos , Ivermectina , Liposomas , Tamaño de la Partícula , SARS-CoV-2 , Ivermectina/farmacología , Ivermectina/química , Antivirales/farmacología , Antivirales/química , Portadores de Fármacos/química , SARS-CoV-2/efectos de los fármacos , Liberación de Fármacos , Animales , Composición de Medicamentos , Tratamiento Farmacológico de COVID-19RESUMEN
The COVID-19 pandemic revealed the need for therapeutic and pharmaceutical molecule development in a short time with different approaches. Although boosting immunological memory by vaccination was the quickest and robust strategy, still medication is required for the immediate treatment of a patient. A popular approach is the mining of new therapeutic molecules. Peptide-based drug candidates are also becoming a popular avenue. To target whole pathogenic viral agents, peptide libraries can be employed. With this motivation, we have used the 12mer M13 phage display library for selecting SARS-CoV-2 targeting peptides as potential neutralizing molecules to prevent viral infections. Panning was applied with four iterative cycles to select SARS-CoV-2 targeting phage particles displaying 12-amino acid-long peptides. Randomly selected peptide sequences were synthesized by a solid-state peptide synthesis method. Later, selected peptides were analyzed by the quartz crystal microbalance method to characterize their molecular interaction with SARS-CoV-2's S protein. Finally, the neutralization activity of the selected peptides was probed with an in-house enzyme-linked immunosorbent assay. The results showed that scpep3, scpep8, and scpep10 peptides have both binding and neutralizing capacity for S1 protein as a candidate for therapeutic molecule. The results of this study have a translational potential with future in vivo and human studies.