Tunable polymeric micelles for taxane and corticosteroid co-delivery
Saved in:
| Title: | Tunable polymeric micelles for taxane and corticosteroid co-delivery |
|---|---|
| Authors: | Armin Azadkhah Shalmani, Alec Wang, Zaheer Ahmed, Maryam Sheybanifard, Rahaf Mihyar, Eva Miriam Buhl, Michael Pohl, Wim E. Hennink, Fabian Kiessling, Josbert M. Metselaar, Yang Shi, Twan Lammers, Quim Peña |
| Contributors: | Afd Pharmaceutics, Pharmaceutics |
| Source: | Drug Deliv Transl Res Drug Delivery and Translational Research |
| Publisher Information: | Springer Science and Business Media LLC, 2023. |
| Publication Year: | 2023 |
| Subject Terms: | Drug Carriers, Co-loading, Paclitaxel, Polymers, Pharmaceutical Science, Antineoplastic Agents, Taxane, Dexamethasone, 3. Good health, Polyethylene Glycols, Drug Liberation, Nanomedicine, Drug Delivery Systems, Corticosteroid, Polymeric micelles, Humans, Original Article, Taxoids, Paclitaxel/pharmacokinetics [MeSH], Drug combination, Polyethylene Glycols/chemistry [MeSH], Antineoplastic Agents/administration, Polymers/chemistry [MeSH], Dexamethasone/administration, Dexamethasone/chemistry [MeSH], Antineoplastic Agents/chemistry [MeSH], Paclitaxel/administration, Taxoids/administration, Taxoids/pharmacokinetics [MeSH], Humans [MeSH], Drug Delivery Systems [MeSH], Taxoids/chemistry [MeSH], Drug Carriers/chemistry [MeSH], Antineoplastic Agents/pharmacokinetics [MeSH], Polyethylene Glycols/administration, Drug Liberation [MeSH], Particle Size [MeSH], Micelles [MeSH], Paclitaxel/chemistry [MeSH], Particle Size, Micelles |
| Description: | Nanomedicine holds promise for potentiating drug combination therapies. Increasing (pre)clinical evidence is available exemplifying the value of co-formulating and co-delivering different drugs in modular nanocarriers. Taxanes like paclitaxel (PTX) are widely used anticancer agents, and commonly combined with corticosteroids like dexamethasone (DEX), which besides for suppressing inflammation and infusion reactions, are increasingly explored for modulating the tumor microenvironment towards enhanced nano-chemotherapy delivery and efficacy. We here set out to develop a size- and release rate-tunable polymeric micelle platform for co-delivery of taxanes and corticosteroids. We synthesized amphiphilic mPEG-b-p(HPMAm-Bz) block copolymers of various molecular weights and used them to prepare PTX and DEX single- and double-loaded micelles of different sizes. Both drugs could be efficiently co-encapsulated, and systematic comparison between single- and co-loaded formulations demonstrated comparable physicochemical properties, encapsulation efficiencies, and release profiles. Larger micelles showed slower drug release, and DEX release was always faster than PTX. The versatility of the platform was exemplified by co-encapsulating two additional taxane-corticosteroid combinations, demonstrating that drug hydrophobicity and molecular weight are key properties that strongly contribute to drug retention in micelles. Altogether, our work shows that mPEG-b-p(HPMAm-Bz) polymeric micelles serve as a tunable and versatile nanoparticle platform for controlled co-delivery of taxanes and corticosteroids, thereby paving the way for using these micelles as a modular carrier for multidrug nanomedicine. Graphical abstract |
| Document Type: | Article Other literature type |
| File Description: | application/pdf |
| Language: | English |
| ISSN: | 2190-3948 2190-393X |
| DOI: | 10.1007/s13346-023-01465-x |
| Access URL: | https://pubmed.ncbi.nlm.nih.gov/37962836 https://research-portal.uu.nl/en/publications/efc186da-cb97-40f4-b56b-9fb890a66d0f https://doi.org/10.1007/s13346-023-01465-x https://repository.publisso.de/resource/frl:6496063 https://dspace.library.uu.nl/handle/1874/435877 |
| Rights: | CC BY |
| Accession Number: | edsair.doi.dedup.....68fab99ffb480a60d409a6905fd2fdbf |
| Database: | OpenAIRE |
Full Text Finder 
Nájsť tento článok vo Web of Science | Abstract: | Nanomedicine holds promise for potentiating drug combination therapies. Increasing (pre)clinical evidence is available exemplifying the value of co-formulating and co-delivering different drugs in modular nanocarriers. Taxanes like paclitaxel (PTX) are widely used anticancer agents, and commonly combined with corticosteroids like dexamethasone (DEX), which besides for suppressing inflammation and infusion reactions, are increasingly explored for modulating the tumor microenvironment towards enhanced nano-chemotherapy delivery and efficacy. We here set out to develop a size- and release rate-tunable polymeric micelle platform for co-delivery of taxanes and corticosteroids. We synthesized amphiphilic mPEG-b-p(HPMAm-Bz) block copolymers of various molecular weights and used them to prepare PTX and DEX single- and double-loaded micelles of different sizes. Both drugs could be efficiently co-encapsulated, and systematic comparison between single- and co-loaded formulations demonstrated comparable physicochemical properties, encapsulation efficiencies, and release profiles. Larger micelles showed slower drug release, and DEX release was always faster than PTX. The versatility of the platform was exemplified by co-encapsulating two additional taxane-corticosteroid combinations, demonstrating that drug hydrophobicity and molecular weight are key properties that strongly contribute to drug retention in micelles. Altogether, our work shows that mPEG-b-p(HPMAm-Bz) polymeric micelles serve as a tunable and versatile nanoparticle platform for controlled co-delivery of taxanes and corticosteroids, thereby paving the way for using these micelles as a modular carrier for multidrug nanomedicine. Graphical abstract |
|---|---|
| ISSN: | 21903948 2190393X |
| DOI: | 10.1007/s13346-023-01465-x |