Local Delivery and Sustained‐Release of Nitric Oxide Donor Loaded in Mesoporous Silica Particles for Efficient Treatment of Primary Open‐Angle Glaucoma

Abstract

Nitric oxide (NO) donors are ideal drug candidates for reducing intraocular pressure in the treatment of glaucoma. However, poor cornea penetration, short duration of efficacy, and narrow therapeutic index of most NO donors obstruct their clinical applications in glaucoma treatment. This study reports a novel NO donor delivery system based on mesoporous silica nanoparticles that can readily overcome the above difficulties and deliver the NO‐donating drug sodium nitroprusside to the target tissues (trabecular meshwork and Schlemm's canal). Mesoporous silica nanoparticles loaded with sodium nitroprusside can produce more exogenous NO and sustain higher NO concentration in animal eye models, which significantly extend the duration of intraocular pressure reduction from 3 to 48 h with only 1/40 of the dose of sodium nitroprusside solution. These findings open up the possibility of mesoporous silica nanoparticles loading sodium nitroprusside for effective management of ocular hypertension.

Impact of nitric oxide's bidirectional role on glaucoma: focus onHelicobacter pylori–related nitrosative stress

“…The reduced cornea penetration, short duration of efficacy, and limited therapeutic index of most NO donors impede their clinical application in glaucoma therapy. Recent studies reported a novel NO donor delivery system . This method is based on mesoporous silica nanoparticles (MSNs), which may overcome the aforementioned problems and deliver the NO‐donating drug sodium nitroprusside (SNP) to the target tissues, that is, the TM and SC .…”

“…Recent studies reported a novel NO donor delivery system . This method is based on mesoporous silica nanoparticles (MSNs), which may overcome the aforementioned problems and deliver the NO‐donating drug sodium nitroprusside (SNP) to the target tissues, that is, the TM and SC . In this respect, it has been proposed that the SNP−MSNs delivery system can induce more exogenous NO and maintain higher NO levels in animal eye models.…”

“…This may lengthen the period of IOP decrease, which appears to be promising for regulating IOP in patients with POAG and ocular hypertension. Likewise, this system may support the development of a new generation of nanomedicine for diverse clinical applications, including subcutaneous and nasal cavity drug delivery . However, concern about possible long‐term NO toxic overload might limit their therapeutic application; thus, further studies are warranted.…”

Cubic and hexagonal liquid crystal gels for ocular delivery with enhanced effect of pilocarpine nitrate on anti-glaucoma treatment

“…Glaucoma is a progressive optic neuropathy caused by retinal ganglion cell death. As a chronic ophthalmic disease, it is characterized by the elevation of the intraocular pressure (IOP), decrease of retinal sensitivity and optic nerve head changing that ultimately lead to decreased vision (Yu et al., 2015; Hu et al., 2018). High IOP is the leading risk factor for the development and progression of this disease, which could seriously lead to irreversible blindness.…”

“…The elevation of IOP is caused by the imbalance between aqueous humor secretion and drainage (Zhao et al., 2017; Adams et al., 2018). Glaucoma is becoming a major cause of blindness and approximately 80 million individuals by 2020 have been affected worldwide (Hu et al., 2018).…”