Abstract
Purpose :
Anti-inflammatory and anti-infection eye drops are routinely used in clinic to assure better outcomes after cataract surgery, which relies on patients compliance and arises extra cost and inconvenience. However, there is no effective anti-posterior capsule opacification (PCO) eye drops available in clinic so far by now. We aimed to develop a safe drug delivery system carrying dexamethasone(DXMS), moxifloxacin(MOX) and genistein(GEN)-nanostructured lipid carrier(NLC) to provide sustainable release in a special designed time-independent manner in anterior chamber to prevent inflammation, infection and after cataract.
Methods :
We used ultrasonic emulsification method to synthesize GEN-NLC which was modificated by methoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA). DXMS and CaCl2 were mixed with the Gen-NLC to form supramolecular hydrogel，while MOX was mixed with 1% gellan gum and the Gen-NLC. Then these two hydrogels were mixed together to form the final delivery system. Its presentation, release, pharmacological effects in vitro were detected by laser scanning confocal microscopy, CCK-8, flow cytometry, real time-PCR, immunofluorescence, wound healing assay, western blotting.
Results :
The particle size of uncoated GEN-NLC was 28.80nm with a surface charge of -2.63mv on average. The encapsulation percentage of all 3 drugs was over 95%. In vitro release, the drug carrier showed similar drugs release patterns which imitated the clinical use of eye drops. Especially, genistein in this delivery system released sustainably that could last nearly 840h. After released rapidly in 120h, DXMS released slowly but continuously until 720h, while, MOX stopped releasing after 144h. The mPEG-PLA-GEN-NLC drug delivery system can inhibit lens epithelial cells proliferation in a concentration dependent manner (12.5, 25, 50, 75, 100μg/ml of genistein release) and time-dependent manner (12, 24, 48,72h). RT-PCR, WB and Wound Healing assay showed the drug delivery system could effectively inhibit SRA proliferation and Epithelial-Mesenchymal Transition.
Conclusions :
We produce a new delivery system combining GEN-NLC, DXMS and MOX together. The carrier provides sustained and controlled drug release that can replace using eye drops after cataract surgery and inhibit the formation of PCO.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.