Topical ocular delivery of TGF-β1 to the back of the eye: Implications in age-related neurodegenerative diseases

Chiara Bianca Maria Platania, Vincenzo Fisichella, Annamaria Fidilio, Federica Geraci, Francesca Lazzara, Gian Marco Leggio, Salvatore Salomone, Filippo Drago, Rosario Pignatello, Filippo Caraci, Claudio Bucolo

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Abstract

Dysregulation of the transforming growth factor-β1 (TGF-β1)/selected small mother against decapentaplegic (SMAD) pathway can be implicated in development of age-related macular degeneration (AMD), and the delivery of TGF-β1 could be beneficial for AMD. We developed a new ophthalmic formulation of TGF-β1 assessing the ocular pharmacokinetic profile of TGF-β1 in the rabbit eye. Small unilamellar vesicles (SUV) loaded with TGF-β1 were complemented with Annexin V and Ca2+, and the vitreous bioavailability of TGF-β1 was assessed after topical ocular administration by a commercial ELISA kit. We detected high levels of TGF-β1 (Cmax 114.7 ± 12.40 pg/mL) in the vitreous after 60 min (Tmax) from the topical application of the liposomal suspension. Ocular tolerability was also assessed by a modified Draize’s test. The new formulation was well tolerated. In conclusion, we demonstrated that the novel formulation was able to deliver remarkable levels of TGF-β1 into the back of the eye after topical administration. Indeed, this TGF-β1 delivery system may be useful in clinical practice to manage ophthalmic conditions such as age-related macular degeneration, skipping invasive intraocular injections.

Original languageEnglish
Article number2076
JournalInternational Journal of Molecular Sciences
Volume18
Issue number10
DOIs
Publication statusPublished - Oct 1 2017

Keywords

  • Age-related neurodegenerative diseases
  • Liposomes
  • Retina
  • TGF-β1

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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    Platania, C. B. M., Fisichella, V., Fidilio, A., Geraci, F., Lazzara, F., Leggio, G. M., Salomone, S., Drago, F., Pignatello, R., Caraci, F., & Bucolo, C. (2017). Topical ocular delivery of TGF-β1 to the back of the eye: Implications in age-related neurodegenerative diseases. International Journal of Molecular Sciences, 18(10), [2076]. https://doi.org/10.3390/ijms18102076