Neuroprotective Effect of siRNA Entrapped in Hyaluronic Acid-Coated Lipoplexes by Intravitreal Administration
Since the possibility of silencing specific genes linked to retinal degeneration has become a reality with the use of small interfering RNAs (siRNAs), this technology has been widely studied to promote the treatment of several ocular diseases. Despite recent advances, the clinical success of gene si...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/6/845 |
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| author | Marcela Coelho Silva Ribeiro Marcelo Coutinho de Miranda Pricila da Silva Cunha Gracielle Ferreira Andrade Gustavo de Oliveira Fulgêncio Dawidson Assis Gomes Sílvia Ligorio Fialho Frederico Pittella Christine Charrueau Virginie Escriou Armando Silva-Cunha |
| author_facet | Marcela Coelho Silva Ribeiro Marcelo Coutinho de Miranda Pricila da Silva Cunha Gracielle Ferreira Andrade Gustavo de Oliveira Fulgêncio Dawidson Assis Gomes Sílvia Ligorio Fialho Frederico Pittella Christine Charrueau Virginie Escriou Armando Silva-Cunha |
| author_sort | Marcela Coelho Silva Ribeiro |
| collection | DOAJ |
| description | Since the possibility of silencing specific genes linked to retinal degeneration has become a reality with the use of small interfering RNAs (siRNAs), this technology has been widely studied to promote the treatment of several ocular diseases. Despite recent advances, the clinical success of gene silencing in the retina is significantly reduced by inherent anatomical and physiological ocular barriers, and new strategies are required to achieve intraocular therapeutic effectiveness. In this study, we developed lipoplexes, prepared with sodium alginate as an adjuvant and strategically coated with hyaluronic acid (HA-LIP), and investigated the potential neuroprotective effect of these systems in a retinal light damage model. Successful functionalization of the lipoplexes with hyaluronic acid was indicated in the dynamic light scattering and transmission electron microscopy results. Moreover, these HA-LIP nanoparticles were able to protect and deliver siRNA molecules targeting caspase-3 into the retina. After retinal degeneration induced by high light exposure, in vitro and in vivo quantitative reverse transcription-PCR (RT-qPCR) assays demonstrated significant inhibition of caspase-3 expression by HA-LIP. Furthermore, these systems were shown to be safe, as no evidence of retinal toxicity was observed by electroretinography, clinical evaluation or histology. |
| first_indexed | 2024-03-10T10:38:12Z |
| format | Article |
| id | doaj.art-8f87b978110f4a0d9e3b2f52bda499e0 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T10:38:12Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-8f87b978110f4a0d9e3b2f52bda499e02023-11-21T23:11:07ZengMDPI AGPharmaceutics1999-49232021-06-0113684510.3390/pharmaceutics13060845Neuroprotective Effect of siRNA Entrapped in Hyaluronic Acid-Coated Lipoplexes by Intravitreal AdministrationMarcela Coelho Silva Ribeiro0Marcelo Coutinho de Miranda1Pricila da Silva Cunha2Gracielle Ferreira Andrade3Gustavo de Oliveira Fulgêncio4Dawidson Assis Gomes5Sílvia Ligorio Fialho6Frederico Pittella7Christine Charrueau8Virginie Escriou9Armando Silva-Cunha10Faculdade de Farmácia, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, BrazilDepartamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, BrazilDepartamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, BrazilDepartamento de Ciências da Saúde, Universidade Federal do Espírito Santo, 29932-540 São Mateus, BrazilFaculdade de Farmácia, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, BrazilDepartamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, BrazilDiretoria de Pesquisa e Desenvolvimento, Fundação Ezequiel Dias, 30510-010 Belo Horizonte, BrazilDepartamento de Ciências Farmacêuticas, Universidade Federal de Juiz de Fora, 36036-900 Juiz de Fora, BrazilUniversité de Paris, CNRS, INSERM, UTCBS, Unité des Technologies Chimiques et Biologiques pour la Santé, 75006 Paris, FranceUniversité de Paris, CNRS, INSERM, UTCBS, Unité des Technologies Chimiques et Biologiques pour la Santé, 75006 Paris, FranceFaculdade de Farmácia, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, BrazilSince the possibility of silencing specific genes linked to retinal degeneration has become a reality with the use of small interfering RNAs (siRNAs), this technology has been widely studied to promote the treatment of several ocular diseases. Despite recent advances, the clinical success of gene silencing in the retina is significantly reduced by inherent anatomical and physiological ocular barriers, and new strategies are required to achieve intraocular therapeutic effectiveness. In this study, we developed lipoplexes, prepared with sodium alginate as an adjuvant and strategically coated with hyaluronic acid (HA-LIP), and investigated the potential neuroprotective effect of these systems in a retinal light damage model. Successful functionalization of the lipoplexes with hyaluronic acid was indicated in the dynamic light scattering and transmission electron microscopy results. Moreover, these HA-LIP nanoparticles were able to protect and deliver siRNA molecules targeting caspase-3 into the retina. After retinal degeneration induced by high light exposure, in vitro and in vivo quantitative reverse transcription-PCR (RT-qPCR) assays demonstrated significant inhibition of caspase-3 expression by HA-LIP. Furthermore, these systems were shown to be safe, as no evidence of retinal toxicity was observed by electroretinography, clinical evaluation or histology.https://www.mdpi.com/1999-4923/13/6/845lipoplexeshyaluronic acidsiRNAcaspase-3retinal neuroprotectionintravitreal administration |
| spellingShingle | Marcela Coelho Silva Ribeiro Marcelo Coutinho de Miranda Pricila da Silva Cunha Gracielle Ferreira Andrade Gustavo de Oliveira Fulgêncio Dawidson Assis Gomes Sílvia Ligorio Fialho Frederico Pittella Christine Charrueau Virginie Escriou Armando Silva-Cunha Neuroprotective Effect of siRNA Entrapped in Hyaluronic Acid-Coated Lipoplexes by Intravitreal Administration Pharmaceutics lipoplexes hyaluronic acid siRNA caspase-3 retinal neuroprotection intravitreal administration |
| title | Neuroprotective Effect of siRNA Entrapped in Hyaluronic Acid-Coated Lipoplexes by Intravitreal Administration |
| title_full | Neuroprotective Effect of siRNA Entrapped in Hyaluronic Acid-Coated Lipoplexes by Intravitreal Administration |
| title_fullStr | Neuroprotective Effect of siRNA Entrapped in Hyaluronic Acid-Coated Lipoplexes by Intravitreal Administration |
| title_full_unstemmed | Neuroprotective Effect of siRNA Entrapped in Hyaluronic Acid-Coated Lipoplexes by Intravitreal Administration |
| title_short | Neuroprotective Effect of siRNA Entrapped in Hyaluronic Acid-Coated Lipoplexes by Intravitreal Administration |
| title_sort | neuroprotective effect of sirna entrapped in hyaluronic acid coated lipoplexes by intravitreal administration |
| topic | lipoplexes hyaluronic acid siRNA caspase-3 retinal neuroprotection intravitreal administration |
| url | https://www.mdpi.com/1999-4923/13/6/845 |
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