## 8 Chitosan-Based Nanoparticles for Posterior Segment of Eye  
* **Glaucoma** It is estimated rgat approximately 80 million people worldwide will suffer from irreversible blindness due to glaucoma by 2020 [64]. One of the major risk factors of glaucoma is the increase in intraocular pressure (IOP) which is due to the disparity between the secretion and drainage mechanism of aqueous humor. Timolol maleate is one of the FDA-approved topical formulations used as an anti-glaucoma agent. Glycoslated chitosan, which is synthesized by covalently linking D-galactose units to chitosan, exhibits better cell compatibility, water-solubility, ocular tolerance, drug loading, and release characteristics, and the pH of the formulation was closer to the physiological pH of the eye, making it a promising approach for administering an array of beta-adrenergic blockers [65]. A novel colloidal system with a diameter ranging between 100-1000 nm Solid lipid nanoparticles consisting of inner solid lipid core are being explored as drug carrier systems for ocular delivery. This carrier system can encompass lipophilic drugs, which struggle to penetrate the corneal barrier. Solid lipid nanoparticles (SLN), when loaded with methazolamide, have significantly reduced the intraocular pressure, thus acting as effective treatment as an anti-glaucoma agent [66]. However, despite the potential of SLN to act as drug carriers, the major challenge to address is poor retention characteristics. This is due to the negative charge present on SLN which limits its interaction with the negatively charged corneal surface. The rationale is to invert the charge of SLN by applying chitosan coatings, which is a cationic polysaccharide. During the fabrication process, it was observed that factors like the amount of methazolamide loaded, phospholipid content, and emulsifier concentration can affect the nanoparticle formulation [67]. Carteolol, a beta blocker, is a drug of choice in the treatment of glaucoma but is limited due to its low bioavailability. Chitosan nanoparticles loaded with carteolol showed better spread and retention properties as compared to the conventional aqueous carteolol solution in the precorneal space [68].  
Evidence has suggested that the inflammation and oxidative stress that arises due to the cell dysfunction of trabecular meshwork increases resistance to the outflow of aqueous humor [69]. This increased intraocular pressure is the major risk factor for glaucoma. In recent years, many antioxidants like quercetin and resveratrol, which act as free radicle scavengers, have been tested as a therapeutic aid for the treatment of glaucoma [70; 71]. Research findings have indicated that, due to a better penetration across the cornea, the efficiency of resveratrol encapsulated PEG-modified chitosan nanoparticles increases significantly. In addition, quercetin, which competitively inhibits the expression of P- glycoprotein in mucosa, increases the bioavailability of resveratrol. PEG-modified chitosan polymer was used to form a dual-drug delivery device for administration at the same time [72]. Naturally obtained from the roots of Coleus Forskolin, a diterpene alkaloid has been investigated to reduce the intraocular pressure in the eye. The use of Forskolin can prove an alternative for patients sensitive to treatment with conventional beta-blockers [73]. The use of chitosan nanoparticles coated with poly lactic-co-glycolic acid has improvised the entrapment efficiency of the hydrophobic drug along with increasing the ocular tolerance due to its safe use. These nanoparticles can be fabricated using one-step emulsification and sonification process and thus are cost-effective [74].