Topical drug delivery to retinal pigment epithelium with microfluidizer produced small liposomes

Drug delivery from topically instilled eye drops to the posterior segment of the eye has long been one of the greatest challenges of ocular drug development. We developed methods of Liposome preparation utilizing a microfluidizer to achieve adjustable nanoparticle size (even less than 80 nm) and high loading capacity of plasmid DNA. The microfluidizing process parameters were shown to affect the size of the liposomes. Higher operating pressures and passage for at least 10 times through the microfluidizer produced small liposomes with narrow size distribution. The liposomes were physically stable for several months at +4°C. In vivo distribution of the optimized Liposome formulations in the rat eyes was investigated with confocal microscopy of the histological specimens. Transferrin was used as a targeting ligand directed to retinal pigment epithelium. Size dependent distribution of liposomes to different posterior segment tissues was seen. Liposomes with the diameter less than 80 nm permeated to the retinal pigment epithelium whereas liposomes with the diameter of 100 nm or more were distributed to the choroidal endothelium. Active targeting was shown to be necessary for Liposome retention to the target tissue. In conclusion, these microfluidizer produced small liposomes in eye drops are an attractive option for drug delivery to the posterior segment tissues of the eye.

1,2-dimyristoyl-3-trimethylammonium-propane (PubChem CID: not available); 1,2-dimyristoyl-sn-glycero-3-phosphocholine (PubChem CID: 5459377); 1,2-dioleoyl-3-trimethylammonium-propane (PubChem CID: 6437371); 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-Atto 647N (PubChem CID: 9546744); 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (PubChem CID: 406952); 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide(polyethylene glycol)-2000] (PubChem CID: 406952); Delivery vehicle; Eye drop delivery; Holo-transferrin (PubChem CID: not available); Liposome; Microfluidizer; Retinal pigment epithelium; Targeting; cholesterol (PubChem CID: 5997); egg L-α-phosphatidylcholine (PubChem CID: 24778933); hydrogenated soy L-α-phosphatidylcholine (PubChem CID: 94190).