Poly(l‐Histidine)‐Mediated On‐Demand Therapeutic Delivery of Roughened Ceria Nanocages for Treatment of Chemical Eye Injury

Abstract

Development of topical bioactive formulations capable of overcoming the low bioavailability of conventional eye drops is critically important for efficient management of ocular chemical burns. Herein, a nanomedicine strategy is presented to harness the surface roughness‐controlled ceria nanocages (SRCNs) and poly(l‐histidine) surface coatings for triggering multiple bioactive roles of intrinsically therapeutic nanocarriers and promoting transport across corneal epithelial barriers as well as achieving on‐demand release of dual drugs [acetylcholine chloride (ACh) and SB431542] at the lesion site. Specifically, the high surface roughness helps improve cellular uptake and therapeutic activity of SRCNs while exerting a negligible impact on good ocular biocompatibility of the nanomaterials. Moreover, the high poly(l‐histidine) coating amount can endow the SRCNs with an ≈24‐fold enhancement in corneal penetration and an effective smart release of ACh and SB431542 in response to endogenous pH changes caused by tissue injury/inflammation. In a rat model of alkali burn, topical single‐dose nanoformulation can efficaciously reduce corneal wound areas (19‐fold improvement as compared to a marketed eye drops), attenuate ≈93% abnormal blood vessels, and restore corneal transparency to almost normal at 4 days post‐administration, suggesting great promise for designing multifunctional metallic nanotherapeutics for ocular pharmacology and tissue regenerative medicine.

Preparation of Lutein Nanoparticles by Glycosylation of Saccharides and Casein for Protecting Retinal Pigment Epithelial Cells

“…Using the calcein/PI assay (green and red), it is possible to distinguish between live and dead cells in an in vitro investigation. 53 The non- fluorescent calcein dye permeated by cells is converted into the fluorescent calcein dye by cellular lactase in living cells as a method to determine cell viability. Although PI cannot cross the intact membrane of living cells, it can cross the permeable membrane of dead cells and embed with nucleic acids to produce fluorescence signals.…”

“…Using the calcein/PI assay (green and red), it is possible to distinguish between live and dead cells in an in vitro investigation . The nonfluorescent calcein dye permeated by cells is converted into the fluorescent calcein dye by cellular lactase in living cells as a method to determine cell viability.…”

Two-electron oxidized polyphenol chemistry-inspired superhydrophilic drug-carrying coatings for the construction of multifunctional nasolacrimal duct stents

“…Macrophages, pivotal in innate immunity and internal homeostasis, 41–44 can be preactivated by LPS to simulate the inflammatory response after bacterial infection. 45–48 We cultured macrophages on the surface of different coatings and stimulated them with LPS to investigate the modulatory effects of the PDA/RAP-modified nasolacrimal duct on inflammation.…”

Unveiling the Power of Gabapentin-Loaded Nanoceria with Multiple Therapeutic Capabilities for the Treatment of Dry Eye Disease

“…Cerium nanospheres have been reported as therapeutic agents and bioactive nanocarriers that can synergistically enhance various therapeutic effects. − ,, Therefore, we investigated the bioactive properties, of Ce and Ce-TGs in vitro , including their antioxidant, anti-inflammatory, antiangiogenic, antiapoptotic, and neuroprotective properties, to determine the performance of various thiolated therapeutic nanocarriers. The antioxidant activities of Ce-TGs were evaluated in a cellular model of hydrogen peroxide (HP)-induced oxidative stress using a DCFH-DA (2′,7′-dichlorodihydrofluorescein diacetate) assay to measure the production of intracellular ROS.…”