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Chemical Structure| 67881-98-5

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Lee, Jeonghun ; Toujani, Chiraz ; Tang, Yao ; Lee, Rahmi ; Cureño Hernandez, Karla E ; Guilliams, Bradley F , et al.

Abstract: Kinetic aspects of the self-assembly process of block copolymers are of great interest, as they can direct assembly through specific pathways, yielding nonequilibrium states with complex and unprecedented nanostruc_x005f_x0002_tures. Assembly kinetics of diblock bottlebrushes was shown to influence the material properties of their solid-state nanostructures, yet little is known regarding their solution-based structures. Herein, we target the nonequilibrium self-assembly of nanoparticles from a zwitterionic diblock bottlebrush consisting of poly(D,L-lactide) and poly(2-methacryloyloxyethyl phosphorylcholine) side-chains. Triggered by a large and rapid change in solvent quality, we examine the resulting nonequilibrium structures (nanoparticles) and their equilibrium analogues (micelles). Using a combination of microscopy and light scattering methods as well as molecular simulations, we gain a microscopic understanding of the experimentally observed differences between the two systems. Compared to micelles, nanoparticles were observed to have a considerably lower aggregation number (accurately predicted by micellar evolution kinetics) and more frustrated core-block packing, along with a lower surface density of hydrophilic chains. Both types of assemblies possessed excellent hemocompatibility and colloidal stability under physiological conditions, concentrated salt solutions, and elevated temperature cycling. Encapsulation of a biopharmaceutics classification system (BCS) class II drug showed superior drug loading capacities and efficiencies for nanoparticles that were not achievable by micelles. In essence, this research provides insight regarding the effects of assembly and stabilization kinetics of zwitterionic bottlebrushes, laying the groundwork for future optimization as a drug delivery platform.

Keywords: assembly kinetics ; bottlebrush copolymer ; zwitterionic polymers ; nanoparticles ; micelles ; drug delivery

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Hernandez, Karla E Cureno ; Lee, Jeonghun ; Kim, Sunghoon ; Cartwright, Zach ; Herrera-Alonso, Margarita ;

Abstract: Mucus is a substance that acts as a protective barrier, shielding tissues from infections caused by viruses and bacteria. Recent studies highlight the advantages of transmucosal drug delivery compared to traditional delivery methods. However, external particles in mucus struggle to penetrate its deeper layers and are often eliminated by mucus clearance mechanisms, hindering effective drug delivery. To gain a deeper understanding of how material surfaces interact with mucus, we grafted brushes of poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) onto silica surfaces, followed by the straightforward installation of a terminal boronic acid moiety (3-phenylboronic acid, APBA). The modification process was carried out following a surface-initiated activator regenerated by electron transfer atom transfer radical polymerization (SI-ARGET ATRP), a method known for its effectiveness in producing well-defined grafted polymers. After conjugation of APBA, we studied the effects of surface chemistry on properties such as pH-sensitivity and mucin adsorption. The surfaces modified with the zwitterionic polymer showed no mucin interaction regardless of system pH. However, all the surfaces containing the boronic acid showed boronic acid–sialic acid interactions, particularly at lower pH values. The insights gained from this study will enhance our understanding of the interactions between the zwitterionic PMPC and the boronic acid APBA with mucins, laying the groundwork for future chemical modifications of particle surfaces aimed at modulating their transport through mucus.

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Lee, Jeonghun ; Tang, Yao ; Cureño Hernandez, Karla E ; Kim, Sunghoon ; Lee, Rahmi ; Cartwright, Zachary , et al.

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, , 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

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Alternative Products

Product Details of 2-Methacryloyloxyethyl phosphorylcholine

CAS No. :67881-98-5
Formula : C11H22NO6P
M.W : 295.27
SMILES Code : O=P(OCCOC(C(C)=C)=O)([O-])OCC[N+](C)(C)C
MDL No. :MFCD11112180
InChI Key :ZSZRUEAFVQITHH-UHFFFAOYSA-N
Pubchem ID :128934

Safety of 2-Methacryloyloxyethyl phosphorylcholine

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
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

Application In Synthesis of 2-Methacryloyloxyethyl phosphorylcholine

* 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.

  • Downstream synthetic route of [ 67881-98-5 ]

[ 67881-98-5 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 142-90-5 ]
  • [ 923-26-2 ]
  • [ 2530-85-0 ]
  • [ 67881-98-5 ]
  • polymer, obtained by copolymerization initiated with AIBN; monomer(s): 2-methacryloyloxyethylphosphorylcholine, 23 mol%; lauryl methacrylate, 47 mol%; 2-hydroxypropyl methacrylate, 25 mol%; trimethoxysilylpropyl methacrylate, 5 mol% [ No CAS ]
  • 2
  • [ 142-90-5 ]
  • [ 923-26-2 ]
  • [ 2530-85-0 ]
  • [ 67881-98-5 ]
  • polymer, obtained by copolymerization initiated with AIBN; monomer(s): 2-methacryloyloxyethylphosphorylcholine, 47 mol%; lauryl methacrylate, 23 mol%; 2-hydroxypropyl methacrylate, 25 mol%; trimethoxysilylpropyl methacrylate, 5 mol% [ No CAS ]
 

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