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...
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MDPI AG
2022-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/16/9382 |
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| author | Manuela-Ramona (Blanaru) Ozturk Marcel Popa Delia Mihaela Rata Anca Niculina Cadinoiu Frederique Parfait Christelle Delaite Leonard Ionut Atanase Carmen Solcan Oana Maria Daraba |
| author_facet | Manuela-Ramona (Blanaru) Ozturk Marcel Popa Delia Mihaela Rata Anca Niculina Cadinoiu Frederique Parfait Christelle Delaite Leonard Ionut Atanase Carmen Solcan Oana Maria Daraba |
| author_sort | Manuela-Ramona (Blanaru) Ozturk |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T13:15:09Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T13:15:09Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0ca01214b3fa48f8bebfab1b8efd43dd2023-11-30T21:36:45ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012316938210.3390/ijms23169382Drug-Loaded Polymeric Micelles Based on Smart Biocompatible Graft Copolymers with Potential Applications for the Treatment of GlaucomaManuela-Ramona (Blanaru) Ozturk0Marcel Popa1Delia Mihaela Rata2Anca Niculina Cadinoiu3Frederique Parfait4Christelle Delaite5Leonard Ionut Atanase6Carmen Solcan7Oana Maria Daraba8Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania“Cristofor Simionescu” Faculty of Chemical Engineering and Environmental Protection, “Gheorghe Asachi” Technical University of Iasi, 700050 Iasi, RomaniaFaculty of Medical Dentistry, “Apollonia” University of Iasi, 700511 Iasi, RomaniaFaculty of Medical Dentistry, “Apollonia” University of Iasi, 700511 Iasi, RomaniaLPIM, Université de Haute Alsace, 68100 Mulhouse, FranceLPIM, Université de Haute Alsace, 68100 Mulhouse, FranceAcademy of Romanian Scientists, 050045 Bucharest, RomaniaPublic Health Department, Faculty of Veterinary Medicine, “Ion Ionescu de la Brad” University of Life Sciences, 700490 Iasi, RomaniaFaculty of Medical Dentistry, “Apollonia” University of Iasi, 700511 Iasi, RomaniaGlaucoma 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.https://www.mdpi.com/1422-0067/23/16/9382glaucomaintraocular pressurepolymeric micellesdorzolamideindomethacincytotoxicity |
| spellingShingle | Manuela-Ramona (Blanaru) Ozturk Marcel Popa Delia Mihaela Rata Anca Niculina Cadinoiu Frederique Parfait Christelle Delaite Leonard Ionut Atanase Carmen Solcan Oana Maria Daraba Drug-Loaded Polymeric Micelles Based on Smart Biocompatible Graft Copolymers with Potential Applications for the Treatment of Glaucoma International Journal of Molecular Sciences glaucoma intraocular pressure polymeric micelles dorzolamide indomethacin cytotoxicity |
| 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 | glaucoma intraocular pressure polymeric micelles dorzolamide indomethacin cytotoxicity |
| url | https://www.mdpi.com/1422-0067/23/16/9382 |
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