期刊
ADVANCED SCIENCE
卷 -, 期 -, 页码 -出版社
WILEY
DOI: 10.1002/advs.202302174
关键词
enhanced pharmacological bioavailability; eye injury therapy; multifunctional biomaterial system; smart drug delivery; surface engineering
Development of topical bioactive formulations capable of overcoming low bioavailability of conventional eye drops is crucial for effective treatment of ocular chemical burns. In this study, a nanomedicine strategy utilizing surface roughness-controlled ceria nanocages (SRCNs) and poly(l-histidine) surface coatings is proposed to achieve multiple bioactive functions of therapeutic nanocarriers, enhance transport across corneal epithelial barriers, and enable on-demand release of dual drugs. The nanoformulation was found to effectively reduce corneal wound areas, attenuate abnormal blood vessels, and restore corneal transparency, demonstrating great potential for ocular pharmacology and tissue regenerative medicine.
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 approximate to 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 approximate to 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.
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