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Felicity De Cogan, Peter Morgan-Warren, Lisa J Hill, Robert A H Scott, Ann Logan; Cell-penetrating peptide constructs as non-invasive drug delivery vehicles for ranibizumab and bevacizumab.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4147.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate cell penetrating peptide constructs (CPPCs), with a protein transduction domain, as novel topical ocular drug delivery vehicles that transport macromolecule biopharmaceutical agents into the posterior segment of the eye.
CPPCs were synthesised using standard solid phase peptide synthesis. Synthesised CPPCs were mixed with Ovalbumin-Texas Red (OVA-TR), a macromolecule used as a drug model for ranibizumab, in PBS to create macromolecule carrying eye drops. The loaded and unloaded CPPC eye drops were topically administered to the adult rat cornea in vivo. The concentration of CPPC and of macromolecule loaded CPPCs that passed into retinal tissue was quantified.
When delivered as an eye drop formulation, fluorescently labelled unloaded CPPCs were capable of penetrating the retina from topical application to the cornea. CPPC levels were determined using fluorescence spectroscopy, with significantly higher fluorescence measured in the retina of unloaded CPPC treated eyes (23.76 ± 4.4 %) when compared to the background signal (12.99 ± 2.9 %), (p=0.045) obtained from the retina of untreated eyes. OVA-TR loaded CPPCs were used to deliver OVA-TR to the retina following topical administration to the front of the eye. The measured macromolecule concentration of OVA-TR in the retina, determined by absorbance of the conjugated tag, was 0.5 ± 0.1 µg at 120 minutes following topical application, significantly higher than levels in control untreated eyes (p=0.036).
CPPCs: (1), are non-toxic to ocular cells in vitro and in vivo; (2), are capable of decorating large macromolecules ; (3), enabled macromolecules to penetrate ocular tissue in vivo; (4), delivered µg quantities of macromolecules to the anterior and posterior segments in vivo. In summary, topically administered CPPC eye drops effectively deliver physiologically relevant concentrations of macromolecules to the anterior and posterior segments of rat eyes in vivo.
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