Figure 6. CDEX NPC peptide ester prodrug extends anti-CNV effect.

(A) Pyrrolydyl-3OH ester of PEDF 336 (PE-336), was carbamate-conjugated to glucose OH groups in CDEX, giving prodrug NPC-PE-(336)₄₀, with ζ = +2.3 mV (Table 2). (A) Representation at left shows NPC prodrug adherence to IVT HA by multivalent ionic interaction (Melgar-Asensio et al., 2018), purple arrows point to sites of spontaneous ester hydrolysis. Released peptide at 154 days (taken as 95% completion of hydrolysis) and at earlier incubation times was measured via UV spectra of ultrafiltrates. Un-hydrolyzed prodrug ester covalently attached to NPC at these times was: % remaining = 100–100 × (0.295 - OD_275nm ultrafiltrate)/(0.295), with calculated release t_1/2 of 35 +/− 5 days based on one phase exponential decay analysis by GraphPad Prism version 5, GraphPad Software, La Jolla, CA. Semi-log loss of free PEDF 336 is shown on the right under physiological conditions in buffer. (B) IVT injection was carried out 14 days prior to laser induction. For free peptide this was 2 μL containing 4 nmoles of PEDF 336. CDEX-336 injection was 2 μL containing 2 nmoles of free peptide and 1.3 nmoles (1.5 μg) of peptide as prodrug in (4.3 μg NPC), expected daily peptide release approximately 20–30 ng. CNV was estimated as described at 28 days post-injection, only the NPC prodrug mixture showed statistically significant CNV reduction (**P< 0.01).