Efficient ocular delivery of siRNA via pH-sensitive vehicles for corneal neovascularization inhibition.

Corneal neovascularization (CoNV)-induced blindness is an enduring and challenging condition with limited management options. Small interfering RNA (siRNA) is a promising strategy for preventing CoNV. This study reported a new strategy using siVEGFA to silence vascular endothelial growth factor A (VEGFA) for CoNV treatment. To improve the efficacy of siVEGFA delivery, a pH-sensitive polycationic mPEG2k-PAMA30-P(DEA29-D5A29) (TPPA) was fabricated. TPPA/siVEGFA polyplexes enter cells via clathrin-mediated endocytosis, resulting in higher cellular uptake efficiency and comparable silencing efficiency than that of Lipofectamine 2000 in vitro. Hemolytic assays verified that TPPA safe in normal physiological environments (pH 7.4) but can easily destroy membranes in acidic mature endosomes (pH 4.0). Studies on the distribution of TPPA in vivo showed that it could prolong the retention time of siVEGFA and promote its penetration in the cornea. In a mouse model induced by alkali burn, TPPA efficiently delivered siVEGFA to the lesion site and achieved VEGFA silencing efficiency. Importantly, the inhibitory effect of TPPA/siVEGFA on CoNV was comparable to that of the anti-VEGF drug ranibizumab. Delivering siRNA using pH-sensitive polycations to the ocular environment provides a new strategy to efficiently inhibit CoNV.

Rapid and Economical Drug-Eluting IOL Preparation via Thermoresponsive Agarose Coating for Effective Posterior Capsular Opacification Prevention.

Posterior capsular opacification (PCO), the highest incidence complication after cataract surgery, is mainly due to the attachment, proliferation, and migration of the residual lens epithelial cells (LECs). Although the drug-eluting IOLs have been proved to be an effective way to prevent PCO incidence, its preparations are time consuming and require tedious preparation steps. Herein, the thermoreversible agarose is adopted to prepare drug-eluting IOL. Such functional coating can be obtained easily by simple immersion in the antiproliferative drug containing hot agarose and taken out for cooling, which not only does not affect the optical property but also can effectively decrease the PCO incidence after intraocular implantation. As a result, the proposed agarose coating provides a rapid and economical alternative of drug-eluting IOL fabrication for PCO prevention.

Drug-free contact lens based on quaternized chitosan and tannic acid for bacterial keratitis therapy and corneal repair.

Bacterial keratitis (BK) and related inflammatory diseases causes irreversible damage to the corneal tissue. In this study, a novel polyacrylamide semi-interpenetrating network hydrogel including quaternized chitosan and tannic acid (PAM-QCS-TA) were used to construct a novel antibacterial and antioxidant contact lens. The obtained hydrogels showed high water content (>85%), swelling resistance, light transmittance (>90%) and adjustable mechanical property. Both quantitative and qualitative antibacterial experiments against Staphylococcus aureus and Escherichia coli (E. coli) indicated excellent sterilization function especially against E. coli (almost 100%). Due to the presence of tannin acid, it showed obvious antioxidant properties, which relieved oxidative stress and protect cells from reactive oxygen species-induced cytotoxicity. Animal experiments also indicated the shortened treatment time of BK (only 3 days) as well as the protection of eye tissue structure. Therefore, such drug-free antibacterial and antioxidant contact lens avoiding the development of drug resistance is a potential candidate in ocular infectious and inflammatory diseases treatment.