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Drug-Loaded Polymeric Micelles Based on Smart Biocompatible Graft Copolymers with Potential Applications for the Treatment of Glaucoma
Glaucoma is the second leading cause of blindness in the world. Despite the fact that many treatments are currently available for eye diseases, the key issue that arises is the administration of drugs for long periods of time and the increased risk of inflammation, but also the high cost of eye surg...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409108/ https://www.ncbi.nlm.nih.gov/pubmed/36012646 http://dx.doi.org/10.3390/ijms23169382 |
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author | Ozturk, Manuela-Ramona (Blanaru) Popa, Marcel Rata, Delia Mihaela Cadinoiu, Anca Niculina Parfait, Frederique Delaite, Christelle Atanase, Leonard Ionut Solcan, Carmen Daraba, Oana Maria |
author_facet | Ozturk, Manuela-Ramona (Blanaru) Popa, Marcel Rata, Delia Mihaela Cadinoiu, Anca Niculina Parfait, Frederique Delaite, Christelle Atanase, Leonard Ionut Solcan, Carmen Daraba, Oana Maria |
author_sort | Ozturk, Manuela-Ramona (Blanaru) |
collection | PubMed |
description | Glaucoma is the second leading cause of blindness in the world. Despite the fact that many treatments are currently available for eye diseases, the key issue that arises is the administration of drugs for long periods of time and the increased risk of inflammation, but also the high cost of eye surgery. Consequently, numerous daily administrations are required, which reduce patient compliance, and even in these conditions, the treatment of eye disease is too ineffective. Micellar polymers are core–shell nanoparticles formed by the self-assembly of block or graft copolymers in selective solvents. In the present study, polymeric micelles (PMs) were obtained by dialysis from smart biocompatible poly(ε-caprolactone)-poly(N-vinylcaprolactam-co-N-vinylpyrrolidone) [PCL-g-P(NVCL-co-NVP)] graft copolymers. Two copolymers with different molar masses were studied, and a good correlation was noted between the micellar sizes and the total degree of polymerisation (DPn) of the copolymers. The micelles formed by Cop A [PCL120-g-P(NVCL507-co-NVP128)], with the lowest total DPn, have a Z-average value of 39 nm, whereas the micellar sizes for Cop B [PCL120-g-P(NVCL1253-co-NVP139)] are around 47 nm. These PMs were further used for the encapsulation of two drugs with applications for the treatment of eye diseases. After the encapsulation of Dorzolamide, a slight increase in micellar sizes was noted, whereas the encapsulation of Indomethacin led to a decrease in these sizes. Using dynamic light scattering, it was proved that both free and drug-loaded PMs are stable for 30 days of storage at 4 °C. Moreover, in vitro biological tests demonstrated that the obtained PMs are both haemo- and cytocompatible and thus can be used for further in vivo tests. The designed micellar system proved its ability to release the encapsulated drugs in vitro, and the results obtained were validated by in vivo tests carried out on experimental animals, which proved its high effectiveness in reducing intraocular pressure. |
format | Online Article Text |
id | pubmed-9409108 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94091082022-08-26 Drug-Loaded Polymeric Micelles Based on Smart Biocompatible Graft Copolymers with Potential Applications for the Treatment of Glaucoma Ozturk, Manuela-Ramona (Blanaru) Popa, Marcel Rata, Delia Mihaela Cadinoiu, Anca Niculina Parfait, Frederique Delaite, Christelle Atanase, Leonard Ionut Solcan, Carmen Daraba, Oana Maria Int J Mol Sci Article Glaucoma is the second leading cause of blindness in the world. Despite the fact that many treatments are currently available for eye diseases, the key issue that arises is the administration of drugs for long periods of time and the increased risk of inflammation, but also the high cost of eye surgery. Consequently, numerous daily administrations are required, which reduce patient compliance, and even in these conditions, the treatment of eye disease is too ineffective. Micellar polymers are core–shell nanoparticles formed by the self-assembly of block or graft copolymers in selective solvents. In the present study, polymeric micelles (PMs) were obtained by dialysis from smart biocompatible poly(ε-caprolactone)-poly(N-vinylcaprolactam-co-N-vinylpyrrolidone) [PCL-g-P(NVCL-co-NVP)] graft copolymers. Two copolymers with different molar masses were studied, and a good correlation was noted between the micellar sizes and the total degree of polymerisation (DPn) of the copolymers. The micelles formed by Cop A [PCL120-g-P(NVCL507-co-NVP128)], with the lowest total DPn, have a Z-average value of 39 nm, whereas the micellar sizes for Cop B [PCL120-g-P(NVCL1253-co-NVP139)] are around 47 nm. These PMs were further used for the encapsulation of two drugs with applications for the treatment of eye diseases. After the encapsulation of Dorzolamide, a slight increase in micellar sizes was noted, whereas the encapsulation of Indomethacin led to a decrease in these sizes. Using dynamic light scattering, it was proved that both free and drug-loaded PMs are stable for 30 days of storage at 4 °C. Moreover, in vitro biological tests demonstrated that the obtained PMs are both haemo- and cytocompatible and thus can be used for further in vivo tests. The designed micellar system proved its ability to release the encapsulated drugs in vitro, and the results obtained were validated by in vivo tests carried out on experimental animals, which proved its high effectiveness in reducing intraocular pressure. MDPI 2022-08-19 /pmc/articles/PMC9409108/ /pubmed/36012646 http://dx.doi.org/10.3390/ijms23169382 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ozturk, Manuela-Ramona (Blanaru) Popa, Marcel Rata, Delia Mihaela Cadinoiu, Anca Niculina Parfait, Frederique Delaite, Christelle Atanase, Leonard Ionut Solcan, Carmen Daraba, Oana Maria Drug-Loaded Polymeric Micelles Based on Smart Biocompatible Graft Copolymers with Potential Applications for the Treatment of Glaucoma |
title | Drug-Loaded Polymeric Micelles Based on Smart Biocompatible Graft Copolymers with Potential Applications for the Treatment of Glaucoma |
title_full | Drug-Loaded Polymeric Micelles Based on Smart Biocompatible Graft Copolymers with Potential Applications for the Treatment of Glaucoma |
title_fullStr | Drug-Loaded Polymeric Micelles Based on Smart Biocompatible Graft Copolymers with Potential Applications for the Treatment of Glaucoma |
title_full_unstemmed | Drug-Loaded Polymeric Micelles Based on Smart Biocompatible Graft Copolymers with Potential Applications for the Treatment of Glaucoma |
title_short | Drug-Loaded Polymeric Micelles Based on Smart Biocompatible Graft Copolymers with Potential Applications for the Treatment of Glaucoma |
title_sort | drug-loaded polymeric micelles based on smart biocompatible graft copolymers with potential applications for the treatment of glaucoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409108/ https://www.ncbi.nlm.nih.gov/pubmed/36012646 http://dx.doi.org/10.3390/ijms23169382 |
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