Neuroprotective Effect of siRNA Entrapped in Hyaluronic Acid-Coated Lipoplexes by Intravitreal Administration

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Silva Ribeiro, Marcela Coelho ^{[1, 2]} ; de Miranda, Marcelo Coutinho ^[3] ; Cunha, Pricila da Silva ^[3] ; Andrade, Gracielle Ferreira ^[4] ; Fulgencio, Gustavo de Oliveira ^[1] ; Gomes, Dawidson Assis ^[3] ; Fialho, Silvia Ligorio ^[5] ; Pittella, Frederico ^[6] ; Charrueau, Christine ^[2] ; Escriou, Virginie ^[2] ; Silva-Cunha, Armando ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Minas Gerais, Fac Farm, BR-31270901 Belo Horizonte, MG - Brazil

^[2] Univ Paris, Unite Technol Chim & Biol Sante, UTCBS, CNRS, INSERM, F-75006 Paris - France

^[3] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, BR-31270901 Belo Horizonte, MG - Brazil

^[4] Univ Fed Espirito Santo, Dept Ciencias Saude, BR-29932540 Sao Mateus - Brazil

^[5] Fundacao Ezequiel Dias, Diretoria Pesquisa & Desenvolvimento, BR-30510010 Belo Horizonte, MG - Brazil

^[6] Univ Fed Juiz de Fora, Dept Ciencias Farmaceut, BR-36036900 Juiz De Fora - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PHARMACEUTICS; v. 13, n. 6 JUN 2021.
• Citações Web of Science: 1

Resumo

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. (AU)

• Processo FAPESP: 14/50928-2 - INCT 2014: Nanotecnologia Farmacêutica: uma abordagem transdisciplinar
• Beneficiário: Maria Vitória Lopes Badra Bentley
• Modalidade de apoio: Auxílio à Pesquisa - Temático