Abstract
Antimicrobial drugs face numerous challenges, including drug resistance, systemic toxic effects, and poor bioavailability. To date, treatment choices are limited, which warrants the search for novel potent antivirals, including those extracted from natural products. The seeds of Peganum harmala L. (Zygophyllaceae family) have been reported to have antimicrobial, antifungal, and anticancer activities. In the present study, a 2-hydroxy propyl-β-cyclodextrin (HPβCD)/harmala alkaloid-rich fraction (HARF) host–guest complex was prepared using a thin-film hydration method to improve the water solubility and bioavailability of HARF. The designed complex was then co-encapsulated with ascorbic acid into PLGA nanoparticles coated with polyethylene glycol (HARF–HPßCD/AA@PLGA-PEG NPs) using the W/O/W multiple emulsion-solvent evaporation method. The average particle size, PDI, and zeta potential were 207.90 ± 2.60 nm, 0.17 ± 0.01, and 31.6 ± 0.20 mV, respectively. The entrapment efficiency for HARF was 81.60 ± 1.20% and for ascorbic acid was 88 ± 2.20%. HARF–HPßCD/AA@PLGA-PEG NPs had the highest antibacterial activity against Staphylococcus aureus and Escherichia coli (MIC of 0.025 mg/mL). They also exhibited high selective antiviral activity against the H1N1 influenza virus (IC50 2.7 μg/mL) without affecting the host (MDCK cells). In conclusion, the co-encapsulation of HPCD–HARF complex and ascorbic acid into PLGA-PEG nanoparticles significantly increased the selective H1N1 killing activity with minimum host toxic effects.
Highlights
Cytopathic effect (CPE) reduction assay was used to evaluate the antiviral activities of plain PLGA-polyethylene glycol (PEG) NPs, harmala alkaloid-rich fraction (HARF), and HARF–hydroxy propyl ß cyclodextrin (HPßCD)/ascorbic acid (AA)@PLGA-PEG NPs in cell culture systems, as described elsewhere with some modifications [42,43]
The 1 H NMR chemical shifts of HPßCD protons in the presence and absence of HARF are presented in protons before and after the formation of the HARF–HPßCD complex
HARF was first mixed with HPßCD as a host molecule to form an inclusion complex
Summary
Numerous nanoplatforms, including liposomes, supramolecular systems, and polymeric nanoparticles, were designed, being reported to remarkably ameliorate the therapeutic activities of different types of biologically active compounds [12,13,14,15,16,17,18] Supramolecular host molecules, such as cyclodextrins (CDs), are involved in overcoming the poor water solubility of the natural compounds via the formation of host–guest complexes. Polymeric nanoparticles (NPs) have been extensively involved in drug delivery, owing to their ability to encapsulate different therapeutically active compounds into their matrix and the ability of their surfaces to be decorated with different functional groups [3,21,22] This could improve the stability of their cargos and prolong their half-lives. The antibacterial and antiviral activities of HARF–HPßCD/AA@PLGA-PEG NPs were evaluated
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