Melatonin (MEL) is a pleiotropic neurohormone of increasing interest as a neuroprotective agent in ocular dis-eases. Improving the mucoadhesiveness is a proposed strategy to increase the bioavailability of topical formu-lations. Herein, the design and optimization of MEL-loaded lipid-polymer hybrid nanoparticles (mel-LPHNs) using Design of Experiment (DoE) was performed. LPHNs consisted of PLGA-PEG polymer nanoparticles coated with a cationic lipid-shell. The optimized nanomedicine showed suitable size for ophthalmic administration (189.4 nm; PDI 0.260) with a positive surface charge (+39.8 mV), high encapsulation efficiency (79.8 %), suitable pH and osmolarity values, good mucoadhesive properties and a controlled release profile. Differential Scanning Calorimetry and Fourier-Transform Infrared Spectroscopy confirmed the encapsulation of melatonin in the systems and the interaction between lipids and polymer matrix. Biological evaluation in an in vitro model of diabetic retinopathy demonstrated enhanced neuroprotective and antioxidant activities of mel-LPHNs, compared to melatonin aqueous solution at the same concentration (0.1 and 1 mu M). A modified Draize test was performed to assess the ocular tolerability of the formulation showing no signs of irritation. To the best our knowledge, this study reported for the first time the development of mel-LPHNs, a novel and safe hybrid platform suitable for the topical management of retinal diseases.

Melatonin loaded hybrid nanomedicine: DoE approach, optimization and in vitro study on diabetic retinopathy model / Romeo, Alessia; Bonaccorso, Angela; Carbone, Claudia; Lupo, Gabriella; Daniela Anfuso, Carmelina; Giurdanella, Giovanni; Caggia, Cinzia; Randazzo, Cinzia; Russo, Nunziatina; Romano, Giovanni Luca; Bucolo, Claudio; Rizzo, Milena; Tosi, Giovanni; Thomas Duskey, Jason; Ruozi, Barbara; Pignatello, Rosario; Musumeci, Teresa. - In: INTERNATIONAL JOURNAL OF PHARMACEUTICS. - ISSN 0378-5173. - 627:(2022), pp. 122195-122195. [10.1016/j.ijpharm.2022.122195]

Melatonin loaded hybrid nanomedicine: DoE approach, optimization and in vitro study on diabetic retinopathy model

Caggia, Cinzia;Randazzo, Cinzia;Bucolo, Claudio;Tosi, Giovanni;Thomas Duskey, Jason;Ruozi, Barbara;
2022

Abstract

Melatonin (MEL) is a pleiotropic neurohormone of increasing interest as a neuroprotective agent in ocular dis-eases. Improving the mucoadhesiveness is a proposed strategy to increase the bioavailability of topical formu-lations. Herein, the design and optimization of MEL-loaded lipid-polymer hybrid nanoparticles (mel-LPHNs) using Design of Experiment (DoE) was performed. LPHNs consisted of PLGA-PEG polymer nanoparticles coated with a cationic lipid-shell. The optimized nanomedicine showed suitable size for ophthalmic administration (189.4 nm; PDI 0.260) with a positive surface charge (+39.8 mV), high encapsulation efficiency (79.8 %), suitable pH and osmolarity values, good mucoadhesive properties and a controlled release profile. Differential Scanning Calorimetry and Fourier-Transform Infrared Spectroscopy confirmed the encapsulation of melatonin in the systems and the interaction between lipids and polymer matrix. Biological evaluation in an in vitro model of diabetic retinopathy demonstrated enhanced neuroprotective and antioxidant activities of mel-LPHNs, compared to melatonin aqueous solution at the same concentration (0.1 and 1 mu M). A modified Draize test was performed to assess the ocular tolerability of the formulation showing no signs of irritation. To the best our knowledge, this study reported for the first time the development of mel-LPHNs, a novel and safe hybrid platform suitable for the topical management of retinal diseases.
2022
627
122195
122195
Melatonin loaded hybrid nanomedicine: DoE approach, optimization and in vitro study on diabetic retinopathy model / Romeo, Alessia; Bonaccorso, Angela; Carbone, Claudia; Lupo, Gabriella; Daniela Anfuso, Carmelina; Giurdanella, Giovanni; Caggia, Cinzia; Randazzo, Cinzia; Russo, Nunziatina; Romano, Giovanni Luca; Bucolo, Claudio; Rizzo, Milena; Tosi, Giovanni; Thomas Duskey, Jason; Ruozi, Barbara; Pignatello, Rosario; Musumeci, Teresa. - In: INTERNATIONAL JOURNAL OF PHARMACEUTICS. - ISSN 0378-5173. - 627:(2022), pp. 122195-122195. [10.1016/j.ijpharm.2022.122195]
Romeo, Alessia; Bonaccorso, Angela; Carbone, Claudia; Lupo, Gabriella; Daniela Anfuso, Carmelina; Giurdanella, Giovanni; Caggia, Cinzia; Randazzo, Cin...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1302988
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