7. Solid lipid nanoparticles for eye targeting

The eye is one of the delicate organs of human and one of the most delicate routes of drug delivery. However, the eye poses unique challenges relative to drug delivery due to the ocular anatomical and physiological constraints. SLNs are one of the promising targeted DDS for an eye. Numerous drugs such as antibiotics, plasmids, anti-inflammatory, and immunosuppressive agents were encapsulated in SLNs for the treatment of ophthalmic disorders.

#### 7.1 Solid lipid nanoparticles for active eye targeting

Corneal neovascularization (CNV), a sight-threatening condition is caused due to various inflammatory settings including chemical injury. Single-stranded proline-modified short hairpin anti-angiopoietin-like protein 2 (ANGPTL2 RNA) interference molecules acts as potent angiogenic and pro-inflammatory factor and is used for the treatment of CNV [61]. Thus, ANGPTL2 RNA loaded SLNs were developed to deliver the interference molecule specifically to the retina. The singlestranded RNAi (pshRNA) loaded SLNs exhibit high stability in vivo and preliminary data suggest that pshRNA is less susceptible to degeneration due to RNase activity. The fluorescence-labeled developed SLNs eye drops penetrated all layers of cornea and expression of ANGPTL2mRNA was considerably inhibited in both epithelium and stroma. Further, the area of angiogenesis was remarkably decreased in the corneas by the SLNs drops as compared to the control group [62].

X-linked juvenile retinoschisis (XJR), a retinal degenerative disorder caused by mutation in the RS1 gene encoding a retinoschisin [63]. Among non-viral vectors, solid lipid nanoparticles (SLNs) represent one of the most effective lipid-based colloidal carriers, and for gene delivery to the posterior segment of the eye [64]. Plasmid (human RS1 gene) loaded SLNs were developed for the treatment of XJR diseases which showed significant improvement of the retinal structure with photoreceptor specific expression of the RS1 gene [65].

Tobramycin (TMC) is one of the most preferable drugs to treat vitreoretinal diseases, such as bacterial infections, endophthalmitis, cytomegalovirus retinitis (CMV), uveitis, proliferative vitreoretinopathy (PVR), diabetic retinopathy, agerelated macular degeneration [66]. Thus TMC loaded mucoadhesive SLNs were developed which showed higher bioaccumulation of drugs in most of the ocular tissues and was able to penetrate into the retina. Moreover, it resulted in enhanced intraphagocytic antibiotic concentration in polymorphonuclear granulocytes and superior bactericidal activity against Pseudomonas aeruginosa. The developed SLNs showed good stability up to 12 months with no aggregation or precipitation phenomena, variations in zeta potential values or in amount of the drug encapsulated into the nanoparticles [67].

#### 7.2 Solid lipid nanoparticles for passive eye targeting

#### 7.2.1 Chitosan coated solid lipid nanoparticles

Indomethacin (IMC), a topical non-steroidal anti-inflammatory drug (NSAID) is used for ocular inflammatory disorders such as conjunctivitis, uveitis, cystoid macular edema, and anterior segment inflammation, including post-operative pain
