PurposeNeuroprotection‐based strategies may be exploited to treat diabetic retinopathy (DR). Our aim is to establish a method for magnetic nanoparticle (MNP)‐mediated delivery of neuroprotectants to the retina, expecting a prolonged therapeutic action. In the first phase of this project, we assessed the bioavailability and bioactivity of the neuroprotectant octreotide (OCT), a somatostatin analog, delivered as OCT‐MNP.MethodsThe effects of OCT‐MNP and those of free OCT (fOCT) were evaluated in in vitro assays using human retinal endothelial cells (HRECs), in H2O2‐treated ex vivo retinal explants, and in vivo in untreated or in kainate‐injected mouse eyes. In the in vitro assays, vascular endothelial growth factor (VEGF)‐induced HREC proliferation, migration and tube formation were assessed. In the ex vivo and in vivo models, qPCR, histochemical and immunohistochemical techniques were used.ResultsIn HRECs, 1 µM OCT‐MNP displayed the same efficacy of 1 µM fOCT in inhibiting VEGF‐induced changes. In H2O2‐treated explants, both 1 µM OCT‐MNP and 1 µM fOCT inhibited apoptosis. In particular, the efficacy of OCT‐MNP was detected at concentrations as low as 0.001 µM. After intraocular injection in mouse eyes, OCT‐MNP were localized to the retinal pigment epithelium and they did not induce any apoptotic sign in the retina. 1 µM OCT‐MNP or fOCT co‐delivered via intraocular injection with 100 µM kainate similarly protected the retina from apoptosis.ConclusionsOCT‐MNP maintain the functional properties of fOCT, in particular its neuroprotective capabilities. Intraocularly injected OCT‐MNP are not toxic. They penetrate the retina, where they may release OCT in a sustained manner. Although needing confirmatory observations, these preliminary data are encouraging for a possible use of MNP‐mediated drug delivery to treat DR.

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