TY - JOUR
T1 - Topical ocular delivery of TGF-β1 to the back of the eye
T2 - Implications in age-related neurodegenerative diseases
AU - Platania, Chiara Bianca Maria
AU - Fisichella, Vincenzo
AU - Fidilio, Annamaria
AU - Geraci, Federica
AU - Lazzara, Francesca
AU - Leggio, Gian Marco
AU - Salomone, Salvatore
AU - Drago, Filippo
AU - Pignatello, Rosario
AU - Caraci, Filippo
AU - Bucolo, Claudio
PY - 2017/10/1
Y1 - 2017/10/1
N2 - 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.
AB - 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.
KW - Age-related neurodegenerative diseases
KW - Liposomes
KW - Retina
KW - TGF-β1
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UR - http://www.scopus.com/inward/citedby.url?scp=85030700854&partnerID=8YFLogxK
U2 - 10.3390/ijms18102076
DO - 10.3390/ijms18102076
M3 - Article
AN - SCOPUS:85030700854
SN - 1661-6596
VL - 18
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 10
M1 - 2076
ER -