Research Article

Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028, Barcelona, Spain

Institute of Nanoscience & Nanotechnology (IN2UB), University of Barcelona, 08028, Barcelona, Spain

Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED), 28031, Madrid, Spain

Unit of Synthesis & Biomedical applications of Peptides, IQAC-CSIC, 08034, Barcelona, Spain

‡Authors contributed equally

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Maria José Gómara‡

https://orcid.org/0000-0002-6906-4833

Unit of Synthesis & Biomedical applications of Peptides, IQAC-CSIC, 08034, Barcelona, Spain

‡Authors contributed equally

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Isabel Haro

*Author for correspondence:

E-mail Address: isabel.haro@iqac.csic.es

https://orcid.org/0000-0001-8677-2340

Unit of Synthesis & Biomedical applications of Peptides, IQAC-CSIC, 08034, Barcelona, Spain

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Published Online:23 Aug 2023https://doi.org/10.2217/nnm-2023-0133

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Abstract

Background: Corneal neovascularization is a sight-threatening disease. It can be treated using antiangiogenic and anti-inflammatory compounds. Therefore, atorvastatin (ATV) constitutes a suitable candidate to be administered topically. To attain suitable efficacy, ATV can be encapsulated into custom-developed nanocarriers such as peptide amphiphiles. Methods: Three peptide amphiphiles bearing one, two or four C₁₆-alkyl groups (mC₁₆-Tat_47-57, dC₁₆-Tat_47-57 and qC₁₆-Tat_47-57) were synthesized, characterized and loaded with ATV. Drug release and ocular tolerance were assessed as well as anti-inflammatory and antiangiogenic properties. Results: ATV-qC₁₆-Tat_47-57 showed higher encapsulation efficiency than mC₁₆-Tat_47-57 and dC₁₆-Tat_47-57 and more defined nanostructures. ATV-qC₁₆-Tat_47-57 showed ATV prolonged release with suitable ocular tolerance. Moreover, ATV-qC₁₆-Tat_47-57 was antiangiogenic and prevented ocular inflammation. Conclusion: ATV-qC₁₆-Tat_47-57 constitutes a promising topical medication against corneal neovascularization.

Plain language summary

Corneal neovascularization is an eye disease that affects over 1 million people every year and can lead to blindness. It is caused by inflammation and the unwanted formation of blood vessels in the eye. Current treatments for this disease are not fully effective. Atorvastatin (ATV) is one drug that has been partially successful at treating corneal neovascularization, but it does not stay in the eye long enough and does not mix well with the water-based environment of the eye. To overcome this, ATV was combined with three specially designed nanocarriers. These nanocarriers were peptides, short stretches of protein. They were designed to be amphiphilic, meaning that one section is hydrophilic (literally meaning ‘water loving’) and one section is hydrophobic (‘water hating’). These peptide nanocarriers allowed ATV to stay in the water-based environment of the eye longer. The peptide with the most hydrophobic chains (qC₁₆-Tat_47-57) was able to carry more ATV than the other peptides and produced particles of a desired shape. ATV-qC₁₆-Tat_47-57 nanocarriers were found to release slowly. These nanocarriers were also found to prevent the development of new blood vessels on a membrane in a hen's egg used to mimic the eye. There was also no sign of irritation on this membrane or in the eyes of New Zealand rabbits. These results show ATV-qC₁₆-Tat_47-57 has a prolonged therapeutic effect, prevents the formation of new blood vessels and is tolerated in the eye. ATV-qC₁₆-Tat_47-57 is therefore potentially a more effective alternative to ATV treatment alone.

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A new peptide able to self-assemble encapsulating atorvastatin has been custom synthesized. It was demonstrated to deliver atorvastatin in a prolonged manner and to be therapeutically effective against corneal neovascularization.

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Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 18, No. 17

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Received 10 May 2023

Accepted 26 July 2023

Published online 23 August 2023

Published in print July 2023

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Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/nnm-2023-0133

Author contributions

Conceptualization: I Haro, MJ Gómara and E Sánchez-López; methodology: I Haro, MJ Gómara and E Sánchez-López; formal analysis: I Haro, MJ Gómara and E Sánchez-López; investigation: I Haro, MJ Gómara and E Sánchez-López; resources: I Haro; writing – original draft preparation: E Sánchez-López; writing – review and editing: I Haro, MJ Gómara and E Sánchez-López; supervision: MJ Gómara and I Haro; funding acquisition: I Haro. All authors have read and agreed to the published version of the manuscript.

Acknowledgements

The authors acknowledge M Cortada and AS Clares for their participation. E Sánchez-López acknowledges the support of the Requalification of the Spanish University System Program.

Financial & competing interests disclosure

This research was funded by the Spanish Ministry of Economy, Industry and Competitiveness and the European Regional Development Fund (grants RTI2018-094120-B-I00, PID2021-122216OB-I00 and PID2021-122187NB-C32). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. The project has been approved by the Ethics Committee of Animal Experimentation of the University of Barcelona under the code 326/19.

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Atorvastatin-loaded peptide amphiphiles against corneal neovascularization

Abstract

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References