A polyethylene glycol (PEG) retinylamine
(Ret-NH<sub>2</sub>) conjugate
PEG-GFL-NH-Ret with a glycine-phenylalanine-leucine (GFL) spacer was
synthesized for controlled oral delivery of Ret-NH<sub>2</sub> to
treat retinal degenerative diseases, including Stargardt disease (STGD)
and age-related macular degeneration (AMD). The peptide spacer was
introduced for sustained release of the drug by digestive enzymes
in the gastrointestinal tract. The pharmacokinetics experiments showed
that the PEG conjugate could control the sustained drug release after
oral administration and had much lower nonspecific liver drug accumulation
than the free drug in wild-type female C57BL mice. In the mean time,
the conjugate maintained the same concentration of Ret-NH<sub>2</sub> in the eye as the free drug. Also, PEG-GFL-NH-Ret at a Ret-NH<sub>2</sub> equivalent dose of 25 mg/kg produced complete protection
of <i>Abca4</i><sup>–/–</sup><i>Rdh8</i><sup>–/–</sup> mouse retinas against light-induced
retinal degeneration for 3 days after oral administration, as revealed
by OCT retina imaging, whereas free Ret-NH<sub>2</sub> did not provide
any protection under identical conditions. The polymer conjugate PEG-GFL-NH-Ret
has great potential for controlled delivery of Ret-NH<sub>2</sub> to
the eye for effective protection against retinal degenerative diseases
