Celecoxib/Cyclodextrin Eye Drop Microsuspensions: Evaluation of In Vitro Cytotoxicity and Anti-VEGF Efficacy for Retinal Diseases.

Celecoxib (CCB), a cyclooxygenase-2 inhibitor, is capable of reducing oxidative stress and vascular endothelial growth factor (VEGF) expression in retinal cells and has been shown to be effective in the treatment of diabetic retinopathy and age-related macular degeneration. However, the ocular bioavailability of CCB is hampered due to its very low aqueous solubility. In a previous study, we developed 0.5% (w/v) aqueous CCB eye drop microsuspensions (MS) containing randomly methylated ß-cyclodextrin (RMßCD) or γ-cyclodextrin (γCD) and hyaluronic acid (HA) as ternary CCB/CD/HA nanoaggregates. Both formulations exhibited good physicochemical properties. Therefore, we further investigated their cytotoxicity and efficacy in a human retina cell line in this study. At a CCB concentration of 1000 µg/mL, both CCB/RMßCD and CCB/γCD eye drop MS showed low hemolysis activity (11.1 ± 0.3% or 4.9 ± 0.2%, respectively). They revealed no signs of causing irritation and were nontoxic to retinal pigment epithelial cells. Moreover, the CCB eye drop MS exhibited significant anti-VEGF activity by reducing VEGF mRNA and protein levels compared to CCB suspended in phosphate buffer saline. The ex vivo transscleral diffusion demonstrated that a high quantity of CCB (112.47 ± 37.27 µg/mL) from CCB/γCD eye drop MS was deposited in the porcine sclera. Our new findings suggest that CCB/CD eye drop MS could be safely delivered to the ocular tissues and demonstrate promising eye drop formulations for retinal disease treatment.

Angiogenic property of silk fibroin scaffolds with adipose-derived stem cells on chick chorioallantoic membrane.

Angiogenesis is a crucial step in tissue regeneration and repair. Biomaterials that allow or promote angiogenesis are thus beneficial. In this study, angiogenic properties of salt-leached silk fibroin (SF) scaffolds seeded with human adipose stem cells (hADSCs) were studied using chick chorioallantoic membrane (CAM) as a model. The hADSC-seeded SF scaffolds (SF-hADSC) with the porosity of 77.34 ± 6.96% and the pore diameter of 513.95 ± 4.99 µm were implanted on the CAM of chick embryos that were on an embryonic day 8 (E8) of development. The SF-hADSC scaffolds induced a spoke-wheel pattern of capillary network indicative of angiogenesis, which was evident since E11. Moreover, the ingrowth of blood vessels into the scaffolds was seen in histological sections. The unseeded scaffolds induced the same extent of angiogenesis later on E14. By contrast, the control group could not induce the same extent of angiogenesis. In vitro cytotoxicity tests and in vivo angioirritative study reaffirmed the biocompatibility of the scaffolds. This work highlighted that the biocompatible SF-hADSC scaffolds accelerate angiogenesis, and hence they can be a promising biomaterial for the regeneration of tissues that require angiogenesis.