π-π-Stacked Poly(ε-caprolactone)-<i>b</i>-poly(ethylene glycol) Micelles Loaded with a Photosensitizer for Photodynamic Therapy
To improve the in vivo stability of poly(ε-caprolactone)-<i>b</i>-poly(ethylene glycol) (PCL-PEG)-based micelles and cargo retention by π-π stacking interactions, pendant aromatic rings were introduced by copolymerization of ε-caprolactone with benzyl 5-methyl-2-oxo-1,3-dioxane-5-carboxy...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-04-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/4/338 |
| _version_ | 1827718970327695360 |
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| author | Yanna Liu Marcel H.A.M. Fens Bo Lou Nicky C.H. van Kronenburg Roel F.M. Maas-Bakker Robbert J. Kok Sabrina Oliveira Wim E. Hennink Cornelus F. van Nostrum |
| author_facet | Yanna Liu Marcel H.A.M. Fens Bo Lou Nicky C.H. van Kronenburg Roel F.M. Maas-Bakker Robbert J. Kok Sabrina Oliveira Wim E. Hennink Cornelus F. van Nostrum |
| author_sort | Yanna Liu |
| collection | DOAJ |
| description | To improve the in vivo stability of poly(ε-caprolactone)-<i>b</i>-poly(ethylene glycol) (PCL-PEG)-based micelles and cargo retention by π-π stacking interactions, pendant aromatic rings were introduced by copolymerization of ε-caprolactone with benzyl 5-methyl-2-oxo-1,3-dioxane-5-carboxylate (TMC-Bz). It was shown that the incorporation of aromatic rings yielded smaller micelles (18–30 nm) with better colloidal stability in PBS than micelles without aromatic groups. The circulation time of i.v. injected micelles containing multiple pendant aromatic groups was longer (t½-α: ~0.7 h; t½-β: 2.9 h) than that of micelles with a single terminal aromatic group (t½ < 0.3 h). In addition, the in vitro partitioning of the encapsulated photosensitizer (meta-tetra(hydroxyphenyl)chlorin, mTHPC) between micelles and human plasma was favored towards micelles for those that contained the pendant aromatic groups. However, this was not sufficient to fully retain mTHPC in the micelles in vivo, as indicated by similar biodistribution patterns of micellar mTHPC compared to free mTHPC, and unequal biodistribution patterns of mTHPC and the host micelles. Our study points out that more detailed in vitro methods are necessary to more reliably predict in vivo outcomes. Furthermore, additional measures beyond π-π stacking are needed to stably incorporate mTHPC in micelles in order to benefit from the use of micelles as targeted delivery systems. |
| first_indexed | 2024-03-10T20:34:02Z |
| format | Article |
| id | doaj.art-9051ac5c2dde4cc58b30b741b38ae09d |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T20:34:02Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-9051ac5c2dde4cc58b30b741b38ae09d2023-11-19T21:10:59ZengMDPI AGPharmaceutics1999-49232020-04-0112433810.3390/pharmaceutics12040338π-π-Stacked Poly(ε-caprolactone)-<i>b</i>-poly(ethylene glycol) Micelles Loaded with a Photosensitizer for Photodynamic TherapyYanna Liu0Marcel H.A.M. Fens1Bo Lou2Nicky C.H. van Kronenburg3Roel F.M. Maas-Bakker4Robbert J. Kok5Sabrina Oliveira6Wim E. Hennink7Cornelus F. van Nostrum8Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3508 TB Utrecht, The NetherlandsDepartment of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3508 TB Utrecht, The NetherlandsDepartment of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3508 TB Utrecht, The NetherlandsDepartment of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3508 TB Utrecht, The NetherlandsDepartment of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3508 TB Utrecht, The NetherlandsDepartment of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3508 TB Utrecht, The NetherlandsDepartment of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3508 TB Utrecht, The NetherlandsDepartment of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3508 TB Utrecht, The NetherlandsDepartment of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3508 TB Utrecht, The NetherlandsTo improve the in vivo stability of poly(ε-caprolactone)-<i>b</i>-poly(ethylene glycol) (PCL-PEG)-based micelles and cargo retention by π-π stacking interactions, pendant aromatic rings were introduced by copolymerization of ε-caprolactone with benzyl 5-methyl-2-oxo-1,3-dioxane-5-carboxylate (TMC-Bz). It was shown that the incorporation of aromatic rings yielded smaller micelles (18–30 nm) with better colloidal stability in PBS than micelles without aromatic groups. The circulation time of i.v. injected micelles containing multiple pendant aromatic groups was longer (t½-α: ~0.7 h; t½-β: 2.9 h) than that of micelles with a single terminal aromatic group (t½ < 0.3 h). In addition, the in vitro partitioning of the encapsulated photosensitizer (meta-tetra(hydroxyphenyl)chlorin, mTHPC) between micelles and human plasma was favored towards micelles for those that contained the pendant aromatic groups. However, this was not sufficient to fully retain mTHPC in the micelles in vivo, as indicated by similar biodistribution patterns of micellar mTHPC compared to free mTHPC, and unequal biodistribution patterns of mTHPC and the host micelles. Our study points out that more detailed in vitro methods are necessary to more reliably predict in vivo outcomes. Furthermore, additional measures beyond π-π stacking are needed to stably incorporate mTHPC in micelles in order to benefit from the use of micelles as targeted delivery systems.https://www.mdpi.com/1999-4923/12/4/338polymer micellesphotodynamic therapyin vitro releasecirculation kineticsbiodistribution |
| spellingShingle | Yanna Liu Marcel H.A.M. Fens Bo Lou Nicky C.H. van Kronenburg Roel F.M. Maas-Bakker Robbert J. Kok Sabrina Oliveira Wim E. Hennink Cornelus F. van Nostrum π-π-Stacked Poly(ε-caprolactone)-<i>b</i>-poly(ethylene glycol) Micelles Loaded with a Photosensitizer for Photodynamic Therapy Pharmaceutics polymer micelles photodynamic therapy in vitro release circulation kinetics biodistribution |
| title | π-π-Stacked Poly(ε-caprolactone)-<i>b</i>-poly(ethylene glycol) Micelles Loaded with a Photosensitizer for Photodynamic Therapy |
| title_full | π-π-Stacked Poly(ε-caprolactone)-<i>b</i>-poly(ethylene glycol) Micelles Loaded with a Photosensitizer for Photodynamic Therapy |
| title_fullStr | π-π-Stacked Poly(ε-caprolactone)-<i>b</i>-poly(ethylene glycol) Micelles Loaded with a Photosensitizer for Photodynamic Therapy |
| title_full_unstemmed | π-π-Stacked Poly(ε-caprolactone)-<i>b</i>-poly(ethylene glycol) Micelles Loaded with a Photosensitizer for Photodynamic Therapy |
| title_short | π-π-Stacked Poly(ε-caprolactone)-<i>b</i>-poly(ethylene glycol) Micelles Loaded with a Photosensitizer for Photodynamic Therapy |
| title_sort | π π stacked poly ε caprolactone i b i poly ethylene glycol micelles loaded with a photosensitizer for photodynamic therapy |
| topic | polymer micelles photodynamic therapy in vitro release circulation kinetics biodistribution |
| url | https://www.mdpi.com/1999-4923/12/4/338 |
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