Non-invasive drug delivery systems mediated by nanocarriers and molecular dynamics simulation for posterior eye disease therapeutics: Virtual screening, construction and comparison

Local deliver medication in a non-invasive pattern and attaining a long-term sustained release at ocular regions to minimize side effects is fascinating for treatment and precision medicine, but its rational design remains a challenge. The aim of this study was to analyze the effect of different delivery strategies on drug bioavailability in the posterior segment of the eye. In this study, the results of molecular dynamics (MD) revealed that quercetin (QUE) and curcumin (CUR) have shown superior affinity and tighter binding capacity for the active site of vascular endothelial growth factor (VEGF). Then, developing and comparing lipid-based nanoemulsion (NE) and polymer-based nanomicelles (NM) were modified with novel mPEG-CS to achieve adequate targeting and retention. The results of in vitro biological properties showed that nano-preparations could be successfully absorbed by cells. The result of in vivo pharmacokinetics revealed that two kinds of nano-preparations could prominently enhance the ocular bioavailability of QUE and CUR to different degrees and have a certain sustained-release effect. More importantly, the results showed that the particle size of NE was smaller than that of NM, which would make the drug retention time in the eye short and result in drug loss. Compared with NE, the release rate of NM was slower, and the effect of improving the drug bioavailability was more significant. In addition, the hydrophobic inner core-hydrophilic shell structure of NM and the carbonyl group in Soluplus material played a protective role in maintaining the stability of the drug. In summary, NM has a more significant effect on improving the ocular absorption of drugs, and is expected to become a candidate nanocarrier for non-invasive drug delivery systems and used for the treatment of post-ocular diseases.