Table 3. . Summary of various polymer-based nano scale drug-delivery systems studied in vivo.

Polymers	Drug/dye	Summary	Ref.
Methoxy PEG and poly(D,L-lactide)-based micelles	Pirenzepine	mPEG-hPLA 80/20 weight ratio showed significantly higher permeability, both in vivo and in vitro, in comparison to 50/50 and 40/60 weight ratios	[95]
Methoxy PEG-hexyl-substituted poly(lactide)	Cyclosporine	The formulation was nontoxic (in vitro and in vivo). It had better pharmacokinetic and pharmacodynamic profile in comparison to marketed preparation	[112–114]
Pluronic® F127	Pilocarpine	The mitotic response time was significantly increased in comparison to pilocarpine salt solution	[99]
N-isopropylacrylamide, vinyl pyrrolidone and acrylic acid cross-linked with N, N’-methylene bis-acrylamide-based micelles	Ketorolac	A twofold increase in the transcorneal permeation was observed, in comparison to suspension was observed. The micelles had better therapeutic response in comparison to suspension, in vivo in rabbits	[90]
Micelle based on polyhydroxyethyl-aspartamide with PEG and/or hexadecylamine side chain	Dexamethasone and netilmicin	Transcorneal permeation was significantly increased in the micelles in comparison to suspension	[103]
PEO-PPO-PEO-based micelles	LacZ gene	The gene was delivered to the cornea, in vivo in rabbits	[91]
PEO-PPO-PEO-based micelles	Ketatin 12 and Keratocan	The gene was delivered to the cornea in the mice and rabbits	[92]
Pluronic® F127 and chitosan micelles	Dexamethasone	The pluronic® F127 – chitosan-based micelles demonstrated a 2.4-and 1.4-fold increase in bioavailability in comparison to ocular suspension and Pluronic® F127-based micelles, respectively	[102]
Polyion complex micelles	Dendrimer porphyrin	Increased drug accumulation in neovascularized tissues was observed in comparison to non-neovascularized tissue	[104]
Pluronic® F127	Ciprofloxacin	The drug-loaded Pluronic® F127 micelles had statistically higher area under the concentration in aqueous humor vs time curve in comparison to marketed formulation	[100]
Polycyanoacrylate polymeric nanoparticles	Amikacin sulfate	Greater ocular disposition was achieved with polymeric nanoparticles having dextran as stabilizer in comparison to other stabilizer and the amikacin control solution	[109]
Chitosan hydrochloride and N-carboxymethyl chitosan-based nanoparticles	Ofloxacin	Chitosan hydrochloride showed greater transcorneal penetration as well as intraocular penetration in comparison to carboxymethyl chitosan and marketed eye drops	[115]
PLGA and PLGA-PEG nanoparticles	Melatonin	Melatonin-loaded PLGA-PEG nanoparticles demonstrated extended precorneal residence of melatonin evident by lowering intraocular pressure in rabbit eye up to 8 h with maximum IOP reduction of 5 mmHg, which was significantly lower than melatonin PLGA nanoparticles and solution	[110]
Methoxy PEG Poly(caprolactone)	Pimecrolimus	Methoxy PEG-poly(ϵ-caprolactone) micelles were found to be superior in the in vitro and in vivo experiments	[106]
Positively charged polymer (PEG)-poly(ε-caprolactone)-g-polyethyleneimine-based micelles	Fluorescein diacetate	The micelles demonstrated better corneal penetration as compared with the control nanoparticles and microparticles, which was evident from in vivo studies	[116]
PLGA nanoparticles	Dorzolamide	Dorzolamide nanoparticle showed promising IOP-lowering effect as compared with dorzolamide solution. TPGS being a P-glycoprotein inhibitor might have significantly enhanced permeation across the goat eye corneas and reduced intraocular pressure through cornea in comparison to dorzolamide solution, in vivo in albino rabbit	[111]
Polyvinyl caprolactam-polyvinyl acetate-PEG graft copolymeric micelles	Cyclosporine	The particle size of the nanoparticles ranged from 70 to 78 nm. The formulation was also found to be safe from the in vitro cytotoxic assay, and had excellent tolerance in rabbits	[108]

PEO-PPO-PEO: Poly(oxyethylene)/poly(oxypropylene)/poly(oxyethylene); PLGA: Poly(D,L-lactide-co-glycolide); TPGS: D-α-tocopheryl PEG 1000 succinate.