AI Article Synopsis
- The study focused on creating an optimized self-nanoemulsifying drug delivery system (SNEDDS) for Genkwanin (GKA) to improve its solubility, intestinal absorption, and effectiveness against colitis-associated colorectal cancer (CAC).
- The formulation was developed by testing various oils and surfactants, leading to a successful mixture that enhanced GKA's properties, making it more bioavailable and effective in a mouse model of CAC.
- The optimized GKA-SNEDDS resulted in a remarkable 353.28% increase in bioavailability compared to regular GKA and demonstrated significant improvements in health metrics and inflammation reduction in the experimental model of cancer.
Article Abstract
Purpose: The aim of the present study was to develop an optimized Genkwanin (GKA)-loaded self-nanoemulsifying drug delivery system (SNEDDS) formulation to enhance the solubility, intestinal permeability, oral bioavailability and anti-colitis-associated colorectal cancer (CAC) activity of GKA.
Methods: We designed a SNEDDS comprised oil phase, surfactants and co-surfactants for oral administration of GKA, the best of which were selected by investigating the saturation solubility, constructing pseudo-ternary phase diagrams, followed by optimizing thermodynamic stability, emulsification efficacy, self-nanoemulsification time, droplet size, transmission electron microscopy (TEM), drug release and intestinal permeability. In addition, the physicochemical properties and pharmacokinetics of GKA-SNEDDS were characterized, and its anti-colitis-associated colorectal cancer (CAC) activity and potential mechanisms were evaluated in AOM/DSS-induced C57BL/6J mice model.
Results: The optimized nanoemulsion formula (OF) consists of Maisine CC, Labrasol ALF and Transcutol HP in a weight ratio of 20:60:20 (w/w/w), in which ratio the OF shows multiple improvements, specifically small mean droplet size, excellent stability, fast release properties as well as enhanced solubility and permeability. Pharmacokinetic studies demonstrated that compared with GKA suspension, the relative bioavailability of GKA-SNEDDS was increased by 353.28%. Moreover, GKA-SNEDDS not only significantly prevents weight loss and improves disease activity index (DAI) but also reduces the histological scores of inflammatory cytokine levels as well as inhibiting the formation of colon tumors via inducing tumor cell apoptosis in the AOM/DSS-induced CAC mice model.
Conclusion: Our results show that the developed GKA-SNEDDS exhibited enhanced oral bioavailability and excellent anti-CAC efficacy. In summary, GKA-SNEDDS, using lipid nanoparticles as the drug delivery carrier, can be applied as a potential drug delivery system for improving the clinical application of GKA.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886095 | PMC |
| http://dx.doi.org/10.2147/DDDT.S292417 | DOI Listing |
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