Macromolecular Platform with Super-Cation Enhanced Trans-Cornea Infiltration for Noninvasive Nitric Oxide Delivery in Ocular Therapy
Fan Jia, Liping Li, Yu Fang, Maomao Song, Jiaping Man, Qiao Jin, Yuan Lei, Jian Ji
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 S-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-N-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.