Solid Lipid–Polymer Hybrid Nanoplatform for Topical Delivery of siRNA: In Vitro Biological Activity and Permeation Studies
Small interfering RNA (siRNA) molecules have limited transfection efficiency and stability, necessitating the use of delivery systems to be effective in gene knockdown therapies. In this regard, lipid–polymeric nanocarriers have emerged as a promising class of nanoparticles for siRNA delivery, parti...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-07-01
|
| Series: | Journal of Functional Biomaterials |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-4983/14/7/374 |
| _version_ | 1827732833709326336 |
|---|---|
| author | Margarete Moreno de Araujo Livia Neves Borgheti-Cardoso Fabíola Garcia Praça Priscyla Daniely Marcato Maria Vitória Lopes Badra Bentley |
| author_facet | Margarete Moreno de Araujo Livia Neves Borgheti-Cardoso Fabíola Garcia Praça Priscyla Daniely Marcato Maria Vitória Lopes Badra Bentley |
| author_sort | Margarete Moreno de Araujo |
| collection | DOAJ |
| description | Small interfering RNA (siRNA) molecules have limited transfection efficiency and stability, necessitating the use of delivery systems to be effective in gene knockdown therapies. In this regard, lipid–polymeric nanocarriers have emerged as a promising class of nanoparticles for siRNA delivery, particularly for topical applications. We proposed the use of solid lipid–polymer hybrid nanoparticles (SLPHNs) as topical delivery systems for siRNA. This approach was evaluated by assessing the ability of SLPHNs–siRNA complexes to internalize siRNA molecules and both to penetrate skin layers in vitro and induce gene knocking down in a skin cell line. The SLPHNs were formed by a specific composition of solid lipids, a surfactant polymer as a dispersive agent, and a cationic polymer as a complexing agent for siRNA. The optimized nanocarriers exhibited a spherical shape with a smooth surface. The average diameter of the nanoparticles was found to be 200 nm, and the zeta potential was measured to be +20 mV. Furthermore, these nanocarriers demonstrated excellent stability when stored at 4 °C over a period of 90 days. In vitro and in vivo permeation studies showed that SLPHNs increased the cutaneous penetration of fluorescent-labeled siRNA, which reached deeper skin layers. Efficacy studies were conducted on keratinocytes and fibroblasts, showing that SLPHNs maintained cell viability and high cellular uptake. Furthermore, SLPHNs complexed with siRNA against Firefly luciferase (siLuc) reduced luciferase expression, proving the efficacy of this nanocarrier in providing adequate intracellular release of siRNA for silencing specific genes. Based on these results, the developed carriers are promising siRNA delivery systems for skin disease therapy. |
| first_indexed | 2024-03-11T00:56:33Z |
| format | Article |
| id | doaj.art-48c097adf2264bceb7ead83145905820 |
| institution | Directory Open Access Journal |
| issn | 2079-4983 |
| language | English |
| last_indexed | 2024-03-11T00:56:33Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Functional Biomaterials |
| spelling | doaj.art-48c097adf2264bceb7ead831459058202023-11-18T19:56:34ZengMDPI AGJournal of Functional Biomaterials2079-49832023-07-0114737410.3390/jfb14070374Solid Lipid–Polymer Hybrid Nanoplatform for Topical Delivery of siRNA: In Vitro Biological Activity and Permeation StudiesMargarete Moreno de Araujo0Livia Neves Borgheti-Cardoso1Fabíola Garcia Praça2Priscyla Daniely Marcato3Maria Vitória Lopes Badra Bentley4School of Pharmaceutical Sciences of Ribeirao Preto, University of São Paulo, Av. do Café, s/n, Ribeirão Preto 14040-903, SP, BrazilSchool of Pharmaceutical Sciences of Ribeirao Preto, University of São Paulo, Av. do Café, s/n, Ribeirão Preto 14040-903, SP, BrazilSchool of Pharmaceutical Sciences of Ribeirao Preto, University of São Paulo, Av. do Café, s/n, Ribeirão Preto 14040-903, SP, BrazilSchool of Pharmaceutical Sciences of Ribeirao Preto, University of São Paulo, Av. do Café, s/n, Ribeirão Preto 14040-903, SP, BrazilSchool of Pharmaceutical Sciences of Ribeirao Preto, University of São Paulo, Av. do Café, s/n, Ribeirão Preto 14040-903, SP, BrazilSmall interfering RNA (siRNA) molecules have limited transfection efficiency and stability, necessitating the use of delivery systems to be effective in gene knockdown therapies. In this regard, lipid–polymeric nanocarriers have emerged as a promising class of nanoparticles for siRNA delivery, particularly for topical applications. We proposed the use of solid lipid–polymer hybrid nanoparticles (SLPHNs) as topical delivery systems for siRNA. This approach was evaluated by assessing the ability of SLPHNs–siRNA complexes to internalize siRNA molecules and both to penetrate skin layers in vitro and induce gene knocking down in a skin cell line. The SLPHNs were formed by a specific composition of solid lipids, a surfactant polymer as a dispersive agent, and a cationic polymer as a complexing agent for siRNA. The optimized nanocarriers exhibited a spherical shape with a smooth surface. The average diameter of the nanoparticles was found to be 200 nm, and the zeta potential was measured to be +20 mV. Furthermore, these nanocarriers demonstrated excellent stability when stored at 4 °C over a period of 90 days. In vitro and in vivo permeation studies showed that SLPHNs increased the cutaneous penetration of fluorescent-labeled siRNA, which reached deeper skin layers. Efficacy studies were conducted on keratinocytes and fibroblasts, showing that SLPHNs maintained cell viability and high cellular uptake. Furthermore, SLPHNs complexed with siRNA against Firefly luciferase (siLuc) reduced luciferase expression, proving the efficacy of this nanocarrier in providing adequate intracellular release of siRNA for silencing specific genes. Based on these results, the developed carriers are promising siRNA delivery systems for skin disease therapy.https://www.mdpi.com/2079-4983/14/7/374solid lipid–polymer hybrid nanoparticlessiRNAnucleic acidgene silencingtopical deliveryskin penetration |
| spellingShingle | Margarete Moreno de Araujo Livia Neves Borgheti-Cardoso Fabíola Garcia Praça Priscyla Daniely Marcato Maria Vitória Lopes Badra Bentley Solid Lipid–Polymer Hybrid Nanoplatform for Topical Delivery of siRNA: In Vitro Biological Activity and Permeation Studies Journal of Functional Biomaterials solid lipid–polymer hybrid nanoparticles siRNA nucleic acid gene silencing topical delivery skin penetration |
| title | Solid Lipid–Polymer Hybrid Nanoplatform for Topical Delivery of siRNA: In Vitro Biological Activity and Permeation Studies |
| title_full | Solid Lipid–Polymer Hybrid Nanoplatform for Topical Delivery of siRNA: In Vitro Biological Activity and Permeation Studies |
| title_fullStr | Solid Lipid–Polymer Hybrid Nanoplatform for Topical Delivery of siRNA: In Vitro Biological Activity and Permeation Studies |
| title_full_unstemmed | Solid Lipid–Polymer Hybrid Nanoplatform for Topical Delivery of siRNA: In Vitro Biological Activity and Permeation Studies |
| title_short | Solid Lipid–Polymer Hybrid Nanoplatform for Topical Delivery of siRNA: In Vitro Biological Activity and Permeation Studies |
| title_sort | solid lipid polymer hybrid nanoplatform for topical delivery of sirna in vitro biological activity and permeation studies |
| topic | solid lipid–polymer hybrid nanoparticles siRNA nucleic acid gene silencing topical delivery skin penetration |
| url | https://www.mdpi.com/2079-4983/14/7/374 |
| work_keys_str_mv | AT margaretemorenodearaujo solidlipidpolymerhybridnanoplatformfortopicaldeliveryofsirnainvitrobiologicalactivityandpermeationstudies AT livianevesborgheticardoso solidlipidpolymerhybridnanoplatformfortopicaldeliveryofsirnainvitrobiologicalactivityandpermeationstudies AT fabiolagarciapraca solidlipidpolymerhybridnanoplatformfortopicaldeliveryofsirnainvitrobiologicalactivityandpermeationstudies AT priscyladanielymarcato solidlipidpolymerhybridnanoplatformfortopicaldeliveryofsirnainvitrobiologicalactivityandpermeationstudies AT mariavitorialopesbadrabentley solidlipidpolymerhybridnanoplatformfortopicaldeliveryofsirnainvitrobiologicalactivityandpermeationstudies |