Thermoresponsive GenisteinNLC-dexamethasone-moxifloxacin multi drug delivery system in lens capsule bag to prevent complications after cataract surgery

Abstract

Cataract surgery is the most common intraocular procedure. To decrease postsurgical inflammation, prevent infection and reduce the incidence of secondary cataract, we built a temperature-sensitive drug delivery system carrying dexamethasone, moxifloxacin and genistein nanostructured lipid carrier (GenNLC) modified by mPEG-PLA based on F127/F68 as hydrogel. Characterizations and release profiles of the drug delivery system were studied. In vitro functions were detected by CCK-8 test, immunofluorescence, wound-healing assay, real time-PCR and western blotting. The size of GenNLCs was 39.47 ± 0.69 nm in average with surface charges of − 4.32 ± 0.84 mV. The hydrogel gelation temperature and time were 32 °C, 20 s with a viscosity, hardness, adhesiveness and stringiness of 6.135 Pa.s, 54.0 g, 22.0 g, and 3.24 mm, respectively. Transmittance of the gel-release medium was above 90% (93.44 ± 0.33% to 100%) at range of 430 nm to 800 nm. Moxifloxacin released completely within 10 days. Fifty percent of dexamethasone released at a constant rate in the first week, and then released sustainably with a tapering down rate until day 30. Genistein released slowly but persistently with a cumulative release of 63% at day 40. The thermoresponsive hydrogel inhibited the proliferation, migration and epithelial-mesenchymal transition of SRA 01/04 cells, which were confirmed by testing CCK-8, wound-healing assay, western blot, real time-PCR (RT-PCR) and immunofluorescence. These results support this intracameral thermoresponsive in situ multi-drug delivery system with programmed release amounts and release profiles to cut down the need of eye drops for preventing inflammation or infection and to reduce posterior capsular opacification following cataract surgery.

Recent Progress of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers as Ocular Drug Delivery Platforms

“…Nanostructured lipid carriers have been also an integral component of hybrid drug-delivery platforms , recently included into thermosensitive in situ gel-forming systems [ 188 , 189 ]. An interesting approach is described by Yu et al in two of their studies, elaborating on baicalin NLCs and quercetin NLCs that were subsequently incorporated into dual pH and thermosensitive in situ gels.…”

Recent advances in thermogels for the management of diabetic ocular complications

“…Yan et al designed a different multi-drug thermogelling drug delivery system to be injected into the anterior chamber after cataract surgery to form an in situ gel depot that slowly releases antibiotics, steroids, and anti-PCO agents. 89 A Pluronic hydrogel matrix (26% F127/1.5% F68) was embedded with dexamethasone, moxifloxacin, and genistein-carrying mPEG-PLA functionalized nanostructured lipid carriers (GenNLC) (Fig. 11A).…”

Applications and Recent Developments of Hydrogels in Ophthalmology

“…Yan et al constructed an F127/F68 thermosensitive hydrogel loaded with dexamethasone, moxifloxacin, and genistein nanolipid carriers (GenNLCs). 120 The hydrogel gelation temperature and time were 32 °C and 20 s, respectively. The transmittance of the crystal gel release medium is more than 90% and does not affect eyesight.…”