Search Results (5)

Objectives: Despite having profound therapeutic value, the clinical application of resveratrol is restrained due to its <1% bioavailability, arising from the extensive fast-pass effect along with enterohepatic recirculation. This study aimed to develop a self-emulsifying formulation capable of increasing the bioavailability of resveratrol via lymphatic transport. Methods: The resveratrol–phospholipid complex (RPC) was formed by the solvent evaporation method and characterized by FTIR, DSC, and XRD analyses. The RPC-loaded self-emulsifying drug delivery system (SEDDS) was designed, developed, and optimized using the QbD approach with an emphasis on resveratrol transport through the intestinal lymphatic pathway. The in vivo pharmacokinetic study was investigated in male Wister Albino rats. Results: The FTIR, DSC, and XRD analyses confirmed the RPC formation. The obtained design space provided robustness of prediction within the 95% prediction interval to meet the CQA specifications. An optimal formulation (desirability value of 7.24) provided Grade-A self-emulsion and exhibited a 48-fold bioavailability enhancement compared to the pure resveratrol. The cycloheximide-induced chylomicron flow blocking approach demonstrated that 91.14% of the systemically available resveratrol was transported through the intestinal lymphatic route. Conclusions: This study suggests that an optimal self-emulsifying formulation can significantly increase the bioavailability of resveratrol through lymphatic transport to achieve the desired pharmacological effects. Full article

The development of externally controlled drug delivery systems that can rapidly trigger drug release is widely expected to change the landscape of future drug carriers. In this study, a drug delivery system was developed for on-demand therapeutic effects. The thermoresponsive paraffin film can be loaded on the basis of therapeutic need, including local anesthetic (lidocaine) or topical antibiotic (neomycin), controlled remotely by a portable mini-heater. The application of mild temperature (45 °C) to the drug-loaded paraffin film allowed a rapid stimulus response within a short time (5 min). This system exploits regular drug release and the rapid generation of mild heat to trigger a burst release of 80% within 6 h of any locally administered drug. The in vitro drug release studies and in vivo therapeutic activity were observed for local anesthesia and wound healing using a neomycin-loaded film. The studies demonstrated on-demand drug release with minimized inflammation and microbial infection. This temperature-responsive drug-loaded film can be triggered remotely to provide flexible control of dose magnitude and timing. Our preclinical studies on these remotely adjustable drug delivery systems can significantly improve patient compliance and medical practice. Full article

Oxidative stress is one of the key factors in the pathophysiology of liver disease. The present study aimed to evaluate the potential impact of two antioxidants, namely coenzyme Q10 (CoQ10) and silymarin, on carbon tetrachloride (CCl₄)-induced oxidative stress and hepatic damage in ovariectomized rats. Female Long Evans rats were divided into six groups (n = 6): control, CCl₄, CCl₄ + CoQ10 (200 mg/kg), CCl₄ + silymarin (140 mg/kg), Control + CoQ10, and Control + silymarin. Plasma and tissues from liver and kidney were analyzed for oxidative stress parameters and antioxidant enzyme activities using biochemical assays. Infiltration of inflammatory cells and fibrosis were assessed by histological staining of tissue sections. Both CoQ10 and silymarin significantly lowered serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels that were detected to be higher in CCl₄ rats compared to controls. Significant reduction in CCl₄-induced elevated levels of oxidative stress markers malondialdehyde (MDA), nitric oxide (NO), and advanced protein oxidation product (APOP) was observed with both antioxidants. However, in control rats, CoQ10 and silymarin did not produce a significant effect. Histological analysis revealed that CCl₄ markedly increased the level of inflammatory cells infiltration and fibrosis in liver and kidney tissues, but this was significantly reduced in CCl₄ + CoQ10 and CCl₄ + silymarin groups. Taken together, our results suggest that CoQ10 and silymarin can protect the liver against oxidative damage through improved antioxidant enzyme activities and reduced lipid peroxidation. Thus, supplementation of the aforementioned antioxidants may be useful as a therapeutic intervention to protect liver health in chronic liver diseases. Full article

Novel coronavirus disease (COVID-19) was identified from China in December 2019 and spread rapidly through human-to-human transmission, affecting so many people worldwide. Until now, there has been no specific treatment against the disease and repurposing of the drug. Our investigation aimed to screen potential inhibitors against coronavirus for the repurposing of drugs. Our study analyzed sequence comparison among SARS-CoV, SARS-CoV-2, and MERS-CoV to determine the identity matrix using discovery studio. SARS-CoV-2 M^pro was targeted to generate an E-pharmacophore hypothesis to screen drugs from the DrugBank database having similar features. Promising drugs were used for docking-based virtual screening at several precisions. Best hits from virtual screening were subjected to MM/GBSA analysis to evaluate binding free energy, followed by the analysis of binding interactions. Furthermore, the molecular dynamics simulation approaches were carried out to assess the docked complex’s conformational stability. A total of 33 drug classes were found from virtual screening based on their docking scores. Among them, seven potential drugs with several anticancer, antibiotic, and immunometabolic categories were screened and showed promising MM/GBSA scores. During interaction analysis, these drugs exhibited different types of hydrogen and hydrophobic interactions with amino acid residue. Besides, 17 experimental drugs selected from virtual screening might be crucial for drug discovery against COVID-19. The RMSD, RMSF, SASA, Rg, and MM/PBSA descriptors from molecular dynamics simulation confirmed the complex’s firm nature. Seven promising drugs for repurposing against SARS-CoV-2 main protease (M^pro), namely sapanisertib, ornidazole, napabucasin, lenalidomide, daniquidone, indoximod, and salicylamide, could be vital for the treatment of COVID-19. However, extensive in vivo and in vitro studies are required to evaluate the mentioned drug’s activity. Full article

Carotenoids are natural lipid-soluble antioxidants abundantly found as colorful pigments in fruits and vegetables. At least 600 carotenoids occur naturally, although about 20 of them, including β-carotene, α-carotene, lycopene, lutein, zeaxanthin, meso-zeaxanthin, and cryptoxanthin, are detectable in the human blood. They have distinct physiological and pathophysiological functions ranging from fetal development to adult homeostasis. β-carotene is a precursor of vitamin A that essentially functions in many biological processes including vision. The human macula lutea and eye lens are rich in lutein, zeaxanthin, and meso-zeaxanthin, collectively known as macular xanthophylls, which help maintain eye health and prevent ophthalmic diseases. Ocular carotenoids absorb light from the visible region (400–500 nm wavelength), enabling them to protect the retina and lens from potential photochemical damage induced by light exposure. These natural antioxidants also aid in quenching free radicals produced by complex physiological reactions and, consequently, protect the eye from oxidative stress, apoptosis, mitochondrial dysfunction, and inflammation. This review discusses the protective mechanisms of macular xanthophylls in preventing eye diseases such as cataract, age-related macular degeneration, and diabetic retinopathy. Moreover, some preclinical animal studies and some clinical trials are discussed briefly to understand carotenoid safety and efficacy. Full article