Retinal drug delivery using eyedrop preparations of poly-l-lysine-modified liposomes

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 83; no. 3; pp. 364 - 369
• Main Authors: Sasaki, Hitoshi, Karasawa, Keiichi, Hironaka, Kohei, Tahara, Kohei, Tozuka, Yuichi, Takeuchi, Hirofumi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-04-2013
• Subjects: Animals; Drug Delivery Systems; Eye drop; Liposome; Liposomes; Male; Mice; Ophthalmic Solutions; Poly-l-lysine; Polylysine - chemistry; Posterior segment; Retina; Surface modification; Eye drop; Liposome; Posterior segment; Surface modification; Retina; Poly-l-lysine
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2012.10.014

The poly-l-lysine (PLL) as a liposomal surface modifier enhances the efficiency of submicron-sized liposomal retina delivery by eye drop.
The purpose of this study was to develop surface-modified liposomes that enhance the efficiency of eye drop drug delivery to the retina. Various molecular weights and concentrations of the water-soluble cationic polymer poly-l-lysine (PLL) were used to modify the surface of submicronized (100nm) liposomes. Physicochemical properties of surface-modified liposomes were determined in vitro, and the efficiency of drug delivery to the retina was investigated in vivo. Using coumarin-6 as a model drug and fluorescent marker, we show that liposome surface modification by PLL dramatically increased delivery to mouse retina segments after eye drop administration. However, when PLL of high molecular weight (>30,000) was used at higher concentrations (>0.05%), aggregation of surface-modified liposomes increased particle size and hampered distribution to inner ocular tissues. As a result, the efficiency of drug delivery of these aggregated surface-modified liposomes was the same as unmodified liposomes. The optimal molecular weight and concentration of PLL in drug-delivering liposomes were 15,000–30,000 and 0.005%, respectively. Under these conditions, PLL-modified liposomes were not cytotoxic in corneal or conjunctival cells. In conclusion, surface-modified liposomes have great potential as effective retinal drug delivery carriers in eye drop formulations.