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

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

Biological activities and biosorption potential of red algae (Corallina officinalis) to remove toxic malachite green dye

Abstract This research aims to use eco-friendly Corallina officinalis as an adsorbent for removing harmful malachite green dye streams from industrial effluent, promoting sustainable living and effective microbial growth inhibition. Corallina officinalis biomass was tested for textile dye biosorption, as well as its antibacterial, antioxidant, and cytotoxic properties. The effects of certain parameters, involving pH solution, initial dye concentration, algae dose, and contact time, were investigated on the sorption of dye. Fourier transform infrared spectroscopy and scanning electron microscopy were also used and, the results showed that the functional groups on the surface of algae played an important part in the biosorption process. It was noted that the kinetic data were significantly prominent by the Pseudo-second-order model with regression correlation coefficient $${r}_{2}^{2}$$ r 2 2 values with an average of 0.95232. The biosorption was compatible with both the Freundlich (R2 = 0.9843), and Langmuir (R2 = 0.9653) isotherms, and the maximum removal efficiency for dye reached up to 99.9% in 2 h, 27 °C, stirring speed 120 rpm, pH 6, initial dye concentration 20 mg L−1, and biomass dose 0.03 g L−1. Corallina officinalis had higher antimicrobial activity, with values of minimum inhibitory concentrations ranging from 0.156 to 5 mg mL−1. Corallina officinalis exerted significant radical scavenging activity against tested free radicals. The extract was examined for cytotoxic activity using nine cancer cell lines, which exhibited high cytotoxicity for colon adenocarcinoma with an IC50 value of 25.895 µg mL−1

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

AbstractSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) predisposed to the emergence of worldwide catastrophe that impels the evolution of safe and effective therapeutic system. Polyphenols as resveratrol (RSV) exhibit a well evidenced antiviral activity. Unfortunately, like most phenolic nutraceuticals, RSV suffers from restrained solubility and massive degradation in GIT and liver which in turn prohibit its clinical use. Herein, PEGylated bilosomes (PBs) contain PEGylated edge activator along with the traditional components as (Span 60, cholesterol and bile salts) were proposed to boost both permeability and bioavailability of RSV. The investigation of the prominent effect of the diverse variables on the characteristics of the vesicles and picking of the optimum formula were conducted via construction of 23 factorial experiment. The appraisal of the formulae was conducted on the basis of entrapment efficiency percent (EE%), particle size (PS) and zeta potential (ZP). In addition, the spherical shaped optimal formula (F5) exhibited EE% of 86.1 ± 2.9%, PS of 228.9 ± 8.5 nm, and ZP of −39.8 ± 1.3 mV. The sorted optimum formula (F5) exhibited superior dissolution behaviors, and boosted Caco-2 cells cellular uptake by a round 4.7 folds relative to RSV dispersion. In addition, F5 demonstrated a complete in vitro suppression of SARS-CoV-2 at a concentration 0.48 μg/ml with 6.6 times enhancement in antiviral activity relative to RSV dispersion. The accomplished molecular modeling heavily provided proof for the possible interactions of resveratrol with the key residues of the SARS-CoV2 Mpro enzyme. Finally, F5 could be proposed as a promising oral panel of RSV for curation from SARS-CoV-2 infection

Design, Green Synthesis and Tailoring of Vitamin E TPGS Augmented Niosomal Nano-Carrier of Pyrazolopyrimidines as Potential Anti-Liver and Breast Cancer Agents with Accentuated Oral Bioavailability

VEGF plays a crucial role in cancer development, angiogenesis and progression, principally liver and breast cancer. It is vital to uncover novel chemical candidates of VEGFR inhibitors to develop more potent anti-breast and anti-liver cancer agents than the currently available candidates, sorafenib and regorafenib, that face resistance obstacles and severe side effects. Herein, nine pyrazolopyrimidine derivatives were designed, synthesized as sorafenib and regorafenib analogues and screened for their in vitro cytotoxic and growth inhibition activities against four human cancer cell lines, namely breast cancer (Michigan Cancer Foundation-7 (MCF-7), hepatocellular carcinoma (HCC) type (HepG2), lung carcinoma (A-549) and human colorectal carcinoma-116 (HCT-116)). Among the tested compounds, compounds 1, 2a, 4b and 7 showed the uppermost cytotoxic activities against all aforementioned cell lines with IC50 estimates varying from 6 to 50 µM, among which compound 7 showed the best inhibitory activity on all tested compounds. Stunningly, compound 7 showed the best significant inhibition of the VEGFR-2 protein expression level (72.3%) as compared to the control and even higher than that produced with sorafenib and regorafenib (70.4% and 55.6%, respectively). Modeling studies provided evidence for the possible interactions of the synthesized compounds with the key residues of the ATP binding sites on the hinge region and the “DFG out” motif of VEGFR-2 kinase. Collectively, our present study suggests that pyrazolopyrimidine derivatives are a novel class of anti-cancer drug candidates to inhibit VEGF-VEGFR function. Aspiring to promote constrained aqueous solubility, hence poor oral bioavailability of the developed lead molecule, 7 and 2a-charged D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) surface-coated niosomes were successfully constructed, adopting a thin film hydration technique striving to overcome these pitfalls. A 23 full factorial design was involved in order to investigate the influence of formulation variables: type of surfactant, either Span 60 or Span 40; surfactant:cholesterol ratio (8:2 or 5:5) along with the amount of TPGS (25 mg or 50 mg) on the characteristics of the nanosystem. F2 and S2 were picked as the optimum formula for compounds 2a and 7 with desirability values of 0.907 and 0.903, respectively. In addition, a distinguished improvement was observed in the compound’s oral bioavailability and cytotoxic activity after being included in the nano-TPGS-coated niosomal system relative to the unformulated compound. The nano-TPGS-coated niosomal system increased the hepatocellular inhibitory activity four times fold of compound 7a (1.6 µM) and two-fold of 2a (3 µM) relative to the unformulated compounds (6 µM and 6.2 µM, respectively)

Design, synthesis, anti-inflammatory evaluation, and molecular modelling of new coumarin-based analogs combined curcumin and other heterocycles as potential TNF-α production inhibitors via upregulating Nrf2/HO-1, downregulating AKT/mTOR signalling pathways and downregulating NF-κB in LPS induced macrophages

AbstractPersistent inflammation contributes to various inflammatory conditions. Inflammation-related diseases may be treated by inhibiting pro-inflammatory mediators and cytokines. Curcumin and coumarin derivatives can target signalling pathways and cellular factors to address immune-related and inflammatory ailments. This study involved designing and synthesising three series of coumarin-based analogs that incorporated curcumin and other heterocycles. These analogs were evaluated for their potential as anti-inflammatory agents in LPS-induced macrophages. Among the fourteen synthesised coumarin derivatives, compound 14b, which contained 3,4-dimethoxybenzylidene hydrazinyl, demonstrated the highest anti-inflammatory activity with an EC50 value of 5.32 μM. The anti-inflammatory effects of 14b were achieved by modulating signalling pathways like AKT/mTOR and Nrf2/HO-1, and downregulating NF-kβ, resulting in reduced production of pro-inflammatory cytokines such as IL-6, IL-1β, and TNF-α. The modelling studies revealed that 14b and dexamethasone bind to the same TNF-α pocket, suggesting that 14b has potential as a therapeutic agent superior to dexamethasone for TNF-α