An Overview on Dry Eye Treatment: Approaches for Cyclosporin A Delivery

Table 1

Delivery systems developed for CsA delivery to the eye.

Dosage form/pathway	Delivery system	Advantages	Drawbacks	Reference
Topical Solutions	Oils	High solubilizing CsA capacity	Poor tolerance unfavorable partition	[58–60]
	α-cyclodextrins (α-CD)	Enhanced corneal penetration	Repeated administrations	[61, 62]
	Penetration enhancers	Enhanced corneal penetration	Poor tolerance	[63, 64]
Topical colloidal carriers	Micelles	High corneal concentrations at 24 hours	Poor tolerance Stability of micelles	[65]
	Emulsion negatively charged	Improvement in dry eye symptoms FDA approved	Ocular burning	[24]
	Emulsion positively charged	Enhancement of corneal retention time, high levels in cornea and conjunctiva	Tolerance to be evaluated	[66]
	Microemulsions	Improvement in dry eye symptoms FDA approved		[67]
	PLGA and CD nanoparticles	Enhanced retention time and high cellular uptake	Tolerance to be evaluated	[8]
	PACA nanoparticles	Improved corneal absorption	Poor tolerance	[68]
	Chitosan nanoparticles	Good tolerance, high extraocular concentrations	Natural origin of chitosan	[69, 70]
	Liposomes	High concentrations	Expensive and challenging manufacturing	[66]
	Cys-PEG-SA nanostructured lipid carriers	High concentrations &SR	Tolerance to be evaluated	[71]
Topical solid forms	Collagen shields	Bandage effect, high levels in cornea	Patient discomfort No self application	[72, 73]
	Collagen shields + Liposomes	Slow continuous release, high tissue concentrations	Complex manufacturing methods	[74]
	Punctal Plugs	Double effect of both CsA and the plug extended release up to 3 months	Tolerance to be evaluated	[9]
	Silicone-hydrogel contact lenses	Controlled release	In-vivo release and toxicity tests are required	[10]
Chemically modified drugs/topical	Prodrugs	Good tolerance, soluble in water, high tear concentrations	Aqueus Solubility	[75–77]
Subconjunctival liquids	Microspheres	High levels in cornea and aqueous humor	No benefits compared to free CsA	[78, 79]
	Liposomes	High levels at four days in aqueous humor	No benefits compared to free CsA	[66, 79, 80]
Subkonjunctival/intraocular solid Forms	Biodegradable implants	Four week therapeutics levels in vitreous, prolongation of corneal graft survival	Implant is free in the anterior chamber	[81]
	Nonbiodegradable implants	Controlled release	Surgical removal is necessary	[82]