Gastrointestinal absorption remains indispensable in the systemic delivery of most drugs, even though it presents several challenges that, paradoxically, may also provide opportunities that can be exploited to achieve maximal bioavailability. Drug delivery systems made from nanoparticle carriers and especially, lipid carriers, have the potential to traverse gastrointestinal barriers and deploy in the lymphatic pathway, which aptly, is free from first pass via the liver. Several poorly soluble drugs have presented improved systemic bioavailability when couriered in lipid nanoparticle carriers. In this review, we propose an additional frontier to enhancing the bioavailability of poorly soluble drugs when encapsulated in lipid nano-carriers by imparting muco-adhesion to the particles through application of appropriate polymeric coating to the lipid carrier. The combined effect of gastrointestinal muco-adhesion followed by lymphatic absorption is a promising approach to improving systemic bioavailability of poorly soluble drugs following oral administration. Evidence to the potential of this approach is backed-up by recent studies within the review.
Xanthones are natural secondary metabolites that possess great potential as neuroprotective agents due to their prominent biological effects on Alzheimer's disease (AD). However, their underlying mechanisms in AD remain unclear. This study aimed to systematically review the effects and mechanisms of xanthones in cell culture and animal studies, gaining a better understanding of their roles in AD. A comprehensive literature search was conducted in the Medline and Scopus databases using specific keywords to identify relevant articles published up to June 2023. After removing duplicates, all articles were imported into the Rayyan software. The article titles were screened based on predefined inclusion and exclusion criteria. Relevant full-text articles were assessed for biases using the OHAT tool. The results were presented in tables. Xanthones have shown various pharmacological effects towards AD from the 21 preclinical studies included. Cell culture studies demonstrated the anti-cholinesterase activity of xanthones, which protects against the loss of acetylcholine. Xanthones exhibited neuroprotective effects by promoting cell viability, reducing the accumulation of β-amyloid and tau aggregation. The administration of xanthones in animal models resulted in a reduction in neuronal inflammation by decreasing microglial and astrocyte burden. In terms of molecular mechanisms, xanthones prevented neuroinflammation through the modulation of signaling pathways, including TLR4/TAK1/NF-κB and MAPK pathways. Mechanisms such as activation of caspase-3 and -9 and suppression of endoplasmic reticulum stress were also reported. Despite the various neuroprotective effects associated with xanthones, there are limited studies reported on their underlying mechanisms in AD. Further studies are warranted to fully understand their potential roles in AD.