Ocular drug delivery systems: An overview

Table 1 Summary of recent developments with nanoparticles as ocular drug delivery vehicles

Drug	Polymer	Features
Carboplatin	CH, SA	Carboplatin loaded NPs demonstrated elevated and sustained anti-proliferative activity in a retinoblastoma cell line (Y-79), with IC50 of 0.56 and 0.004 μg/mL for free carboplatin and carboplatin loaded NPs, respectively[49]
5-FU	CH, SA	CH coated SA-CH nanoparticles (CH-SA-CH NPs) loaded with 5-FU showed significantly higher concentration of 5-FU in aqueous humor as compared to SA-CH 5-FU loaded NPs and 5-FU solution. The higher Cmax was achieved in case of CH-SA-CH NPs (24.67 μg/mL) compared to 5-FU solution (6.14 μg/mL)[50]
Sparfloxacin	PLGA	After topical application, sparfloxacin-loaded nanoparticles were retained for a longer duration on the corneal surface as compared to an aqueous solution, which was drained rapidly from the corneal surface. Also, in vitro release studies revealed an extended release of sparfloxacin[51]
BT	Sodium alginate	BT-loaded nanoparticles provided prolong drug release over a period of 8 h after topical instillation to albino rabbits[52]
Levofloxacin	PLGA	The nanosuspensions was retained for the longer time on rabbit eye surface and drained out slowly compared to marketed formulation. Results of ex-vivo transcorneal permeation study across excised goat cornea revealed that levofloxacin from the marketed formulation was permeated 36.9% in 4 h whereas levofloxacin from PLGA nanoparticles was permeated 47.43% in 4 h across cornea[53]
DS	PLGA	An extended DS release was observed from the nanoparticles under in vitro conditions. The developed polymer nanoparticles formulation was non-irritant to cornea, iris, and conjunctiva for as long as 24 h after application[54]
Pilocarpine	PLGA	The in vivo miosis studies showed that the duration of miotic response increased by 40% for the nanoparticles compared to the eye drops[55]
Gatifloxacin/Prednisolone	Eudragit RS 100 and RL 100, coating with hyaluronic acid	In vitro release studies revealed prolonged drug release compared to the free drugs with no burst effect Nanoparticles formulation showed better bioavailability of gatifloxacin in rabbit eye with 1.76 fold increase in Cmax of gatifloxacin in the aqueous humor in comparison to the eye drops[56]
Cloricromene (AD6)	Eudragit	Nanosuspension enhanced stability of the ester drug for several months as compared to an AD6 aqueous solution[57]
Brimonidine Tartrate	Eudragit RS 100 Eudragit RL 100	The AUC (ΔIOP vs time) for the selected nanoparticles formulations were about seven times higher than that of eye drop formulations in rabbit eye[58]

CH: Chitosan; SA: Sodium alginate; 5-FU: 5-Fluorouracil; PLGA: Poly (lactide-co-glycolide); IOP: Intraocular pressure; AUC: Area under the curve; BT: Brimonidine tartrate; DS: Diclofenac sodium.

Table 2 Recent advancements in liposomal ocular drug delivery

Drug	Type of Liposomes	Result
Acetazolamide	Multilamellar, unilamellar	Multilamellar liposomes produced a more significant lowering in IOP in comparison with REVs liposomes[72]
Ciprofloxacin	Multilamellar	The mean residence time of ciprofloxacin was three fold higher for the CS-coated liposomes (3.85 h) compared to commercially available eye drops Ciprocin® (1.39 h)[73]
Cytochrome C		The cytochrome C loaded freeze-dried liposomes exhibited significant efficacy in retarding the onset and progression of cataract formation in rat eye[74]
VIP	Pegylated liposomes	After intravitreal injection, VIP concentration in ocular fluids was 15 times higher for liposomal formulation (155 ± 65 ng/mL) than the solution (10 ± 1 ng/mL), at 24 h[75]
Coumarin-6	Multilamellar	After topical administration in mice, the intensity of coumarin-6 in the retina was much higher with PLL modified liposomes[76]
Bevacizumab (Avastin)		Vitreous concentration of bevacizumab after 42 d of administration was 16 and 3.3 μg/mL in the eyes for liposomal and non-liposomal bevacizumab, respectively. The AUC (conc vs time) for liposomal bevacizumab was 1.5 fold higher compared with non-liposomal bevacizumab[77]
Fluorescence probe (coumarin-6)	Submicron-sized liposomes (ssLips) and multilamellar	After topical instillation of submicron-sized liposomes (ssLips), drug was delivered to the posterior segment ocular tissues including retina[78]
Fluconazole		Antifungal activity of fluconazole in liposomal formulation was better than that of fluconazole solution[79]
Edaravone	Submicron-sized liposomes	Topical administration of edaravone-loaded ssLips protected retina against light-induced dysfunction in mice eye while there was no marked protection found in the group treated with free edaravone[80]
Diclofenac	Multilamellar	Topical administration of diclofenac loaded PVA-R modified liposomes lead to improved retinal delivery in rabbit eye. Concentration of diclofenac in the retina–choroid was enhanced by 1.8 fold in case of drug loaded PVA-R modified liposome compared to that of the diclofenac solution[81]

REVs: Reverse phase evaporation; PLL: Poly-L-lysine; VIP: Vasoactive intestinal peptide; PVA: Polyvinyl alcohol; IOP: Intraocular pressure; AUC: Area under the curve.