Inclusion of a Phytomedicinal Flavonoid in Biocompatible Surface-Modified Chylomicron Mimic Nanovesicles with Improved Oral Bioavailability and Virucidal Activity: Molecular Modeling and Pharmacodynamic Studies

Abstract

Morin hydrate (MH) is a widely-used Asian phytomedicinal flavonoid with a wide range of reported therapeutic activities. However, MH has limited oral bioavailability due to its low aqueous solubility and intestinal permeability, which in turn hinders its potential antiviral activity. The study reported herein was designed to encapsulate MH in polyethyleneglycolated (PEGylated) chylomicrons (PCMs) and to boost its antiviral activity and biological availability for oral administration using a rat experimental model. The PEGylated edge activator combined with the conventional components of chylomicrons (CMs) amplify the transport of the drug across the intestine and its circulation period, hence its therapeutic impact. The implementation of variables in the in vitro characterization of the vesicles was investigated. Using Design Expert® software, a 24 factorial design was conducted, and the resulting PCM formulations were fabricated utilizing a thin-film hydration technique. The efficacy of the formulations was assessed according to their zeta potential (ZP), entrapment efficiency percentage (EE%), amount of drug released after 8 h (Q8h), and particle size (PS) data. Formulation F9, which was deemed to be the optimal formula, used compritol as the lipidic core together in defined amounts with phosphatidylcholine (PC) and Brij52. Computer-aided studies revealed that MH alone in a suspension had both diminished intestinal permeability and absorption, but was enhanced when loaded in PCMs. This was affirmed by the superiority of formulation F9 results in ex vivo permeation and pharmacokinetic studies. Furthermore, formulation F9 had a superior safety profile and antiviral activity over a pure MH suspension. Molecular-docking studies revealed the capability of MH to inhibit MERS-CoV 3CLpro, the enzyme shown to exhibit a crucial role in viral replication. Additionally, F9 suppressed both MERS-CoV-induced histopathological alteration in lung tissue and resulting oxidative and inflammatory biomarkers. Collectively, the results reported herein affirmed the potential of PCMs as nanocarriers for the effective oral administration of MH as an antiviral.

‘Poly phenolic phytoceutical loaded nano-bilosomes for enhanced caco-2 cell permeability and SARS-CoV 2 antiviral activity’: in-vitro and insilico studies

“…Also the statistical analysis revealed that doubling the EA amount from 15 mg to 30 mg resulted in a significant negative impact on the EE% ( p = 0.001). Higher amount of EA predispose to the introduction of more pores within the vesicular structure rendering it more leaky, additionally, the fluidity of the bilayer may be also increased as a consequence of the incorporation of higher amount of EA, subsequently a decline in EE% values could be noticed (Zakaria et al., 2022a ).…”

“…Moreover, the surface active nature of Brij augmented in lowering the interfacial tension of the system, thus increasing its stability and resulted in formation of vesicles of lower PS. In contrary, all these effects will be diminished on using lower amounts of EA and consequently led to enlargement in PS (Abdelbary and AbouGhaly, 2015 ; Zakaria et al., 2022a ).…”

“…The TEM image of F5 declared that the vesicles exhibited round shape devoided from any abnormality Figure 5 . Additionally, a fader color was noticed at the boarders of the vesicles indicating the PEG assembly at the boarders as a coat surrounding the vesicles (Zakaria et al., 2022a ). The absence of any drug crystals could not be observed in the image which came in agreement with the outcome of XRD which affirm the complete inclusion RSV within the vesicles (Abdelbary et al., 2018 ).…”

Atorvastatin-loaded emulsomes foam as a topical antifungal formulation

“…As per the reported method ( Zakaria et al, 2022 ), a thin film hydration technique was used for drug-emulsome incorporation with a slight alteration. Therefore, several atorvastatin-loaded emulsome (ATO-EMLs) formulae were prepared.…”

A Micro-Configured Multiparticulate Reconstitutable Suspension Powder of Fixed Dose Rifampicin and Pyrazinamide: Optimal Fabrication and In Vitro Quality Evaluation

“…The in vitro dissolution experiment was carried out on three separate optimized drug-loaded formulations by modifying previously published methods [ 42 , 43 , 44 , 45 , 46 ]. Drug-loaded suspensions (15 mL) were contained in a cellulose membrane dialysis tubing with a molecular weight cut-off of 14,000 Da (D9402-100FT, Sigma Aldrich, St. Louis, MO, USA) and placed into lidded glass baths containing 500 mL PBS.…”