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Ultrastable and Redispersible Zwitterionic Bottlebrush Micelles for Drug Delivery
Lee, Jeonghun ; Tang, Yao ; Curen?o Hernandez, Karla E , et al. ACS Appl. Mater. Interfaces,2024,16(41):55118-55129. DOI: 10.1021/acsami.4c10968 PubMed ID: 39370599
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Abstract: Bottlebrush copolymers are increasingly used for drug delivery and biological imaging applications in part due to the enhanced thermodynamic stability of their self-assemblies. Herein, we discuss the effect of hydrophilic block chemistry on the stability zwitterionic of bottlebrush micelles. Amphiphilic bottlebrushes with zwitter-ionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)and nonionic polyethylene glycol (PEG) hydrophilic blocks were synthesized by "grafting from" polymerization and self-assembled into well-defined spherical micelles. Colloidal stability and stability against disassembly were challenged under high concentrations of NaCl, MgSO4, sodium dodecyl sulfate, fetal bovine serum, and elevated temperature. While both types of micelles appeared to be stable in many of these conditions, those with a PMPC shell consistently surpassed their PEG analogs. Moreover, when repeatedly subjected to lyophilization/resuspension cycles, PMPC micelles redispersed with no apparent variation in size or dispersity even in the absence of a cryoprotectant; PEG micelles readily aggregated. The observed excellent stability of PMPC micelles is attributed to the low critical micelle concentration of the bottlebrushes as well as to the strong hydration shell caused by ionic solvation of the phosphorylcholine moieties. Zwitterionic micelles were loaded with doxorubicin, and higher loading capacity/efficiency, as well as delayed release, was observed with increasing side-chain length. Finally, hemocompatibility studies of PMPC micelles demonstrated no disruption to the red blood cell membranes. The growing concern regarding the immunogenicity of PEG-based systems propels the search for alternative hydrophilic polymers; in this respect and for their outstanding stability, zwitterionic bottlebrush micelles represent excellent candidates for drug delivery and bioimaging applications.
Keywords: zwitterionic polymers ; amphiphilic bottlebrushes ; drug delivery ; ultrastable nanoparticles ; redispersible nanoparticles
Purchased from AmBeed: 67881-98-5
CAS No. : | 67881-98-5 | MDL No. : | MFCD11112180 |
Formula : | C11H22NO6P | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | ZSZRUEAFVQITHH-UHFFFAOYSA-N |
M.W : | 295.27 | Pubchem ID : | 128934 |
Synonyms : |
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Chemical Name : | 2-(Methacryloyloxy)ethyl (2-(trimethylammonio)ethyl) phosphate |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P233-P260-P261-P264-P271-P280-P302+P352-P304-P304+P340-P305+P351+P338-P312-P321-P332+P313-P337+P313-P340-P362-P403-P403+P233-P405-P501 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.