Macromolecular Platform with Super-Cation Enhanced Trans-Cornea Infiltration for Noninvasive Nitric Oxide Delivery in Ocular Therapy.
basic_science · Level V
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- Record sourced from PubMed, PMID 33289535.
- Also identified by DOI 10.1021/acsnano.0c05977.
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Abstract
The cornea provides important protection for human eyes from invasion of alien substances. However, its blockage on the infiltration of molecules also constitutes a great challenge for noninvasive trans-cornea delivery of drugs. Here we report polyamino acid-based <i>S</i>-nitrosothiols with high cationic charge density as a NO carrier to overcome cornea associated blockage in ophthalmological therapy. Our results demonstrate that the cationic nature of the polymer promoted transcytosis, which greatly enhances the trans-cornea delivery of the NO donor and bypasses cornea barriers on passive drug diffusion. The combination of super cation and glutathione responsiveness synergistically enhanced intraocular delivery of topically administered poly(2-acetamido-<i>N</i>-triethylenetetramine-3-nitrosothiol-3-methylbutanamide)aspartamide, effectively alleviating high intraocular pressure in mice with glaucoma. Such a noninvasive "barrier hopping" approach not only serves as an inspiration in improving the efficiency of trans-cornea drug delivery but also has great potential in overcoming drug transporting barriers in other biomedical applications.