OCULAR DRUG DELIVERY

Despite the higher rate of blindness due to population aging, minimally invasive and selective
drug delivery to the eye still remains an open challenge, especially in the posterior segment. The
posterior eye segment is composed by several cell layers, each one specialized in different functions.
It is affected by several diseases, which account for the majority of blindness worldwide.
One of the most effective routes to reach the eye posterior segment is represented by intravitreal
(IVT) injections. However, current procedures have severe collateral effects due to the need of
repetitive injections over the time, the unfavorable drug kinetics (the initial dose is very high and
quickly drops to zero due to physiological washing), the lack of specificity for the target (all cell
layers are exposed to the drug), etc. In this project we used a drug carrier, with the intent to
release the drug in a specific region or tissue and to prolong its half-life. Specifically, we validated
a carrier based on magnetic nanoparticles (MNPs). We found that magnetic nanoparticle, after intraocular injection, are able to rapidly and persistently localize within the retinal pigment epithelium (RPE) in an autonomously manner. Most importantly, our results show that surface functionalization could change the fate of the particles, driving their localization in different cell layers of the posterior eye chamber, such as the choroid or the retina. We used MNPs to deliver neurotrophic factors, which have a very short half-life in vivo, usually making ineffective their clinical use. We found that the injection of MNPs functionalized with nerve growth factor (NGF) or brain derived nerve factor (BDNF)  prevents injuries to the posterior eye chamber and sustain the regeneration process compared to that obtained using the free factors. We postulate that the
increase in stability and the localization of growth factors mediated by MNPs are responsible for
the enhanced neuroprotective effects of NGF and BDNF in the MNP group compared with the
sham group. Our data suggest that MNP could represent a powerful strategy for the design of
novel minimally invasive carriers for cell-specific ocular delivery and neuroprotection.

MAIN COLLABORATIONS

Prof L Dente, UNIPI

PUBLICATIONS

  • Amato, R., Giannaccini, M., Dal Monte, M., Cammalleri, M., Pini, A., Raffa, V., Lulli, M., Casini, G. Association of the Somatostatin Analog Octreotide With Magnetic Nanoparticles for Intraocular Delivery: A Possible Approach for the Treatment of Diabetic Retinopathy (2020) Frontiers in Bioengineering and Biotechnology, 8, art. no. 144, .DOI: 10.3389/fbioe.2020.00144
  • Giannaccini, M., Usai, A., Chiellini, F., Guadagni, V., Andreazzoli, M., Ori, M., Pasqualetti, M., Dente, L., Raffa, V. Neurotrophin-conjugated nanoparticles prevent retina damage induced by oxidative stress (2018) Cellular and Molecular Life Sciences, 75 (7), pp. 1255-1267. DOI: 10.1007/s00018-017-2691-x
  • Amato, R., Dal Monte, M., Lulli, M., Raffa, V., Casini, G. Nanoparticle-mediated delivery of neuroprotective substances for the treatment of diabetic retinopathy (2018) Current Neuropharmacology, 16 (7), pp. 993-1003. DOI: 10.2174/1570159X15666170717115654
  • Martina Giannaccini, Lucia Pedicini, Guglielma De Matienzo, Federica Chiellini, Luciana Dente, and Vittoria Raffa. Magnetic nanoparticles: a strategy to target the choroidal layer in the posterior segment of the eye. 2017 Scientific Reports 7:43092. IF: 5.578
  • Giannaccini M, Giannini M, Calatayud MP, Goya GF, Cuschieri A, Dente L and Raffa V (2014). Magnetic Nanoparticles as Intraocular Drug Delivery System to Target Retinal Pigmented Epithelium (RPE). International Journal of Molecular Sciences (ISSN 1422-0067) doi:10.3390/ijms150x000x. IF: 2.464