Redox-Responsive Polymersomes as Smart Doxorubicin Delivery Systems
Stimuli-responsive polymersomes have emerged as smart drug delivery systems for programmed release of highly cytotoxic anticancer agents such as doxorubicin hydrochloride (Dox·HCl). Recently, a biodegradable redox-responsive triblock copolymer (mPEG–PDH–mPEG) was synthesized with a central hydrophob...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-08-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/8/1724 |
| _version_ | 1797408411742109696 |
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| author | Carmen Ferrero Marta Casas Isidoro Caraballo |
| author_facet | Carmen Ferrero Marta Casas Isidoro Caraballo |
| author_sort | Carmen Ferrero |
| collection | DOAJ |
| description | Stimuli-responsive polymersomes have emerged as smart drug delivery systems for programmed release of highly cytotoxic anticancer agents such as doxorubicin hydrochloride (Dox·HCl). Recently, a biodegradable redox-responsive triblock copolymer (mPEG–PDH–mPEG) was synthesized with a central hydrophobic block containing disulfide linkages and two hydrophilic segments of poly(ethylene glycol) methyl ether. Taking advantage of the self-assembly of this amphiphilic copolymer in aqueous solution, in the present investigation we introduce a solvent-exchange method that simultaneously achieves polymersome formation and drug loading in phosphate buffer saline (10 mM, pH 7.4). Blank and drug-loaded polymersomes (5 and 10 wt.% feeding ratios) were prepared and characterized for morphology, particle size, surface charge, encapsulation efficiency and drug release behavior. Spherical vesicles of uniform size (120–190 nm) and negative zeta potentials were obtained. Dox·HCl was encapsulated into polymersomes with a remarkably high efficiency (up to 98 wt.%). In vitro drug release studies demonstrated a prolonged and diffusion-driven release at physiological conditions (~34% after 48 h). Cleavage of the disulfide bonds in the presence of 50 mM glutathione (GSH) enhanced drug release (~77%) due to the contribution of the erosion mechanism. Therefore, the designed polymersomes are promising candidates for selective drug release in the reductive environment of cancer cells. |
| first_indexed | 2024-03-09T03:58:06Z |
| format | Article |
| id | doaj.art-ff2cc7656c03488bad5ba6799fabe69b |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T03:58:06Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-ff2cc7656c03488bad5ba6799fabe69b2023-12-03T14:18:00ZengMDPI AGPharmaceutics1999-49232022-08-01148172410.3390/pharmaceutics14081724Redox-Responsive Polymersomes as Smart Doxorubicin Delivery SystemsCarmen Ferrero0Marta Casas1Isidoro Caraballo2Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, C/Prof. García González No. 2, 41012 Sevilla, SpainDepartamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, C/Prof. García González No. 2, 41012 Sevilla, SpainDepartamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, C/Prof. García González No. 2, 41012 Sevilla, SpainStimuli-responsive polymersomes have emerged as smart drug delivery systems for programmed release of highly cytotoxic anticancer agents such as doxorubicin hydrochloride (Dox·HCl). Recently, a biodegradable redox-responsive triblock copolymer (mPEG–PDH–mPEG) was synthesized with a central hydrophobic block containing disulfide linkages and two hydrophilic segments of poly(ethylene glycol) methyl ether. Taking advantage of the self-assembly of this amphiphilic copolymer in aqueous solution, in the present investigation we introduce a solvent-exchange method that simultaneously achieves polymersome formation and drug loading in phosphate buffer saline (10 mM, pH 7.4). Blank and drug-loaded polymersomes (5 and 10 wt.% feeding ratios) were prepared and characterized for morphology, particle size, surface charge, encapsulation efficiency and drug release behavior. Spherical vesicles of uniform size (120–190 nm) and negative zeta potentials were obtained. Dox·HCl was encapsulated into polymersomes with a remarkably high efficiency (up to 98 wt.%). In vitro drug release studies demonstrated a prolonged and diffusion-driven release at physiological conditions (~34% after 48 h). Cleavage of the disulfide bonds in the presence of 50 mM glutathione (GSH) enhanced drug release (~77%) due to the contribution of the erosion mechanism. Therefore, the designed polymersomes are promising candidates for selective drug release in the reductive environment of cancer cells.https://www.mdpi.com/1999-4923/14/8/1724polymersometriblock copolymer mPEG–PDH–mPEGredox-responsivedoxorubicin hydrochloridesmart drug delivery systemsdrug release kinetics |
| spellingShingle | Carmen Ferrero Marta Casas Isidoro Caraballo Redox-Responsive Polymersomes as Smart Doxorubicin Delivery Systems Pharmaceutics polymersome triblock copolymer mPEG–PDH–mPEG redox-responsive doxorubicin hydrochloride smart drug delivery systems drug release kinetics |
| title | Redox-Responsive Polymersomes as Smart Doxorubicin Delivery Systems |
| title_full | Redox-Responsive Polymersomes as Smart Doxorubicin Delivery Systems |
| title_fullStr | Redox-Responsive Polymersomes as Smart Doxorubicin Delivery Systems |
| title_full_unstemmed | Redox-Responsive Polymersomes as Smart Doxorubicin Delivery Systems |
| title_short | Redox-Responsive Polymersomes as Smart Doxorubicin Delivery Systems |
| title_sort | redox responsive polymersomes as smart doxorubicin delivery systems |
| topic | polymersome triblock copolymer mPEG–PDH–mPEG redox-responsive doxorubicin hydrochloride smart drug delivery systems drug release kinetics |
| url | https://www.mdpi.com/1999-4923/14/8/1724 |
| work_keys_str_mv | AT carmenferrero redoxresponsivepolymersomesassmartdoxorubicindeliverysystems AT martacasas redoxresponsivepolymersomesassmartdoxorubicindeliverysystems AT isidorocaraballo redoxresponsivepolymersomesassmartdoxorubicindeliverysystems |