Abstract
There is a strong need for innovative and efficient drug delivery systems for ocular therapy development. However, testing intravitreal drug delivery systems without using live animals is challenging. Ex vivo animal models offer an interesting alternative. We analyzed the potential of using fresh porcine eyes obtained from the local slaughterhouse as a model for testing the intravitreal biodistribution and retention of liposomes with or without polyethylene glycol (PEG) conjugation and with different surface charges. The histology of the eyes was analyzed to localize the liposomes, and it was found that liposomes with PEG absorbed rapidly on the retina (within 1 h), with positively charged and PEG-coated liposomes being retained for at least 24 h. In parallel, fluorophotometry was employed on intact eyes, to determine the pharmacokinetics of the fluorophore calcein, as a substitute for a small hydrophilic therapeutic compound. We found a 4.5-fold increase in the vitreous half-life of calcein loaded in liposomes, compared with the free solution. Retinal toxicity was addressed using murine-derived retinal explant cultures. Liposomes were non-toxic up to 500 µg/mL. Toxicity was observed at 5 mg/mL for anionic and cationic liposomes, with 2-fold and 2.5-fold increased photoreceptor cell death, respectively. Overall, we could show that important ocular drug delivery considerations such as pharmacokinetics and biodistribution can be estimated in ex vivo porcine eyes, and may guide subsequent in vivo experiments.
Highlights
Treating retinal diseases with injections into the vitreous body of the eye is common practice in the clinic
Nano-sized liposomes offer promising potential. They are composed of usually well-tolerated lipids, and less material is required to form the liposomes as compared to other colloidal drug delivery systems, which restricts scattering of in-coming light through the vitreous [4]
We found that the formulations were only toxic at high concentrations (5 mg/mL), with cationic liposomes lipid DOTAP, which has been shown to exhibit some cytotoxicity to HeLa cells [35], the formulations Cat-polyethylene glycol (PEG)-Lp and An-PEG-Lp were chosen for the analysis, to assess whether the addition of cationic lipids would cause more cell death to retinal cultures
Summary
Treating retinal diseases with injections into the vitreous body of the eye is common practice in the clinic. Encapsulation of drugs in drug delivery systems can extend the vitreous retention time of the drug, and reduce the injection frequency [3] In this regard, nano-sized liposomes offer promising potential. Liposomes can encapsulate hydrophilic and hydrophobic compounds simultaneously and the surface can be modified, e.g., the surface charge can be fine-tuned or targeting ligands to certain cell types can be conjugated [4,5,6,7]. They are biodegradable, and potentially more safe for repeated applications than non-degradable drug delivery systems like metallic nanoparticles [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
