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Development of a Vinyl Ether-Functionalized Polyphosphoester as a Template for Multiple Postpolymerization Conjugation Chemistries and Study of Core Degradable Polymeric Nanoparticles.

Lim YH, Heo GS, Rezenom YH, Pollack S, Raymond JE, Elsabahy M, Wooley KL - Macromolecules (2014)

Bottom Line: This vinyl ether-functionalized PPE scaffold was coupled with hydroxyl- or thiol-containing model small molecules via three different types of conjugation chemistries-thiol-ene "click" reaction, acetalization, or thio-acetalization reaction-to afford modified polymers that accommodated either stable thio-ether or hydrolytically labile acetal or thio-acetal linkages.Amphiphilic diblock copolymers of poly(ethylene glycol) and PEVEP formed well-defined micelles with a narrow and monomodal size distribution in water, as confirmed by dynamic light scattering (DLS), transmission electron microscopy, and atomic force microscopy.The hydrolytic degradation products of the PEVEP segments of the block copolymers were then identified by electrospray ionization, gas chromatography, and matrix-assisted laser desorption/ionization mass spectrometry.

View Article: PubMed Central - PubMed

Affiliation: Departments of Chemistry, Chemical Engineering, and Materials Science and Engineering, Laboratory for Synthetic-Biologic Interactions, Texas A&M University, P.O. Box 30012, 3255 TAMU, College Station, Texas 77842-3012, United States.

ABSTRACT

A novel polyphosphoester (PPE) with vinyl ether side chain functionality was developed as a versatile template for postpolymerization modifications, and its degradability and biocompatibility were evaluated. An organo-catalyzed ring-opening polymerization of ethylene glycol vinyl ether-pendant cyclic phosphotriester monomer allowed for construction of poly(ethylene glycol vinyl ether phosphotriester) (PEVEP). This vinyl ether-functionalized PPE scaffold was coupled with hydroxyl- or thiol-containing model small molecules via three different types of conjugation chemistries-thiol-ene "click" reaction, acetalization, or thio-acetalization reaction-to afford modified polymers that accommodated either stable thio-ether or hydrolytically labile acetal or thio-acetal linkages. Amphiphilic diblock copolymers of poly(ethylene glycol) and PEVEP formed well-defined micelles with a narrow and monomodal size distribution in water, as confirmed by dynamic light scattering (DLS), transmission electron microscopy, and atomic force microscopy. The stability of the micelles and the hydrolytic degradability of the backbone and side chains of the PEVEP block segment were assessed by DLS and nuclear magnetic resonance spectroscopy ((1)H and (31)P), respectively, in aqueous buffer solutions at pH values of 5.0 and 7.4 and at temperatures of 25 and 37 °C. The hydrolytic degradation products of the PEVEP segments of the block copolymers were then identified by electrospray ionization, gas chromatography, and matrix-assisted laser desorption/ionization mass spectrometry. The parent micelles and their degradation products were found to be non-cytotoxic at concentrations up to 3 mg/mL, when evaluated with RAW 264.7 mouse macrophages and OVCAR-3 human ovarian adenocarcinoma cells.

No MeSH data available.


Related in: MedlinePlus

(a) Rate ofthe PEVEP backbone degradation of 7 atpH 5.0 (black line) or pH 7.4 (red line) at 37 °C as a functionof time, as measured by a comparison of the integrals of initial tothe newly appeared 31P NMR resonances. Changes in the 31P NMR resonance of PEVEP backbone of 7 at pH5.0 (b) and 7.4 (c) at 37 °C over a period of time.
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fig4: (a) Rate ofthe PEVEP backbone degradation of 7 atpH 5.0 (black line) or pH 7.4 (red line) at 37 °C as a functionof time, as measured by a comparison of the integrals of initial tothe newly appeared 31P NMR resonances. Changes in the 31P NMR resonance of PEVEP backbone of 7 at pH5.0 (b) and 7.4 (c) at 37 °C over a period of time.

Mentions: The backbonestability of the PEVEP segment in D2O at pH values of 5.0and 7.4 and temperature of 37 °C was monitored by 31P NMR spectroscopy (Figure 4). The integralratio of the 31P resonance of the intact PEVEP segmentat −0.71 ppm to that of the newly emerging peaks was analyzed.The pH-dependent degradation of the PEVEP backbone linkages becameapparent by the disappearance of 31P resonance correspondingto the intact PEVEP backbone, coincident with the appearance of new 31P resonances as a result of hydrolytic degradation at pH5.0, whereas there was no significant change in the PEVEP 31P resonance when the samples were incubated at pH 7.4.


Development of a Vinyl Ether-Functionalized Polyphosphoester as a Template for Multiple Postpolymerization Conjugation Chemistries and Study of Core Degradable Polymeric Nanoparticles.

Lim YH, Heo GS, Rezenom YH, Pollack S, Raymond JE, Elsabahy M, Wooley KL - Macromolecules (2014)

(a) Rate ofthe PEVEP backbone degradation of 7 atpH 5.0 (black line) or pH 7.4 (red line) at 37 °C as a functionof time, as measured by a comparison of the integrals of initial tothe newly appeared 31P NMR resonances. Changes in the 31P NMR resonance of PEVEP backbone of 7 at pH5.0 (b) and 7.4 (c) at 37 °C over a period of time.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4296319&req=5

fig4: (a) Rate ofthe PEVEP backbone degradation of 7 atpH 5.0 (black line) or pH 7.4 (red line) at 37 °C as a functionof time, as measured by a comparison of the integrals of initial tothe newly appeared 31P NMR resonances. Changes in the 31P NMR resonance of PEVEP backbone of 7 at pH5.0 (b) and 7.4 (c) at 37 °C over a period of time.
Mentions: The backbonestability of the PEVEP segment in D2O at pH values of 5.0and 7.4 and temperature of 37 °C was monitored by 31P NMR spectroscopy (Figure 4). The integralratio of the 31P resonance of the intact PEVEP segmentat −0.71 ppm to that of the newly emerging peaks was analyzed.The pH-dependent degradation of the PEVEP backbone linkages becameapparent by the disappearance of 31P resonance correspondingto the intact PEVEP backbone, coincident with the appearance of new 31P resonances as a result of hydrolytic degradation at pH5.0, whereas there was no significant change in the PEVEP 31P resonance when the samples were incubated at pH 7.4.

Bottom Line: This vinyl ether-functionalized PPE scaffold was coupled with hydroxyl- or thiol-containing model small molecules via three different types of conjugation chemistries-thiol-ene "click" reaction, acetalization, or thio-acetalization reaction-to afford modified polymers that accommodated either stable thio-ether or hydrolytically labile acetal or thio-acetal linkages.Amphiphilic diblock copolymers of poly(ethylene glycol) and PEVEP formed well-defined micelles with a narrow and monomodal size distribution in water, as confirmed by dynamic light scattering (DLS), transmission electron microscopy, and atomic force microscopy.The hydrolytic degradation products of the PEVEP segments of the block copolymers were then identified by electrospray ionization, gas chromatography, and matrix-assisted laser desorption/ionization mass spectrometry.

View Article: PubMed Central - PubMed

Affiliation: Departments of Chemistry, Chemical Engineering, and Materials Science and Engineering, Laboratory for Synthetic-Biologic Interactions, Texas A&M University, P.O. Box 30012, 3255 TAMU, College Station, Texas 77842-3012, United States.

ABSTRACT

A novel polyphosphoester (PPE) with vinyl ether side chain functionality was developed as a versatile template for postpolymerization modifications, and its degradability and biocompatibility were evaluated. An organo-catalyzed ring-opening polymerization of ethylene glycol vinyl ether-pendant cyclic phosphotriester monomer allowed for construction of poly(ethylene glycol vinyl ether phosphotriester) (PEVEP). This vinyl ether-functionalized PPE scaffold was coupled with hydroxyl- or thiol-containing model small molecules via three different types of conjugation chemistries-thiol-ene "click" reaction, acetalization, or thio-acetalization reaction-to afford modified polymers that accommodated either stable thio-ether or hydrolytically labile acetal or thio-acetal linkages. Amphiphilic diblock copolymers of poly(ethylene glycol) and PEVEP formed well-defined micelles with a narrow and monomodal size distribution in water, as confirmed by dynamic light scattering (DLS), transmission electron microscopy, and atomic force microscopy. The stability of the micelles and the hydrolytic degradability of the backbone and side chains of the PEVEP block segment were assessed by DLS and nuclear magnetic resonance spectroscopy ((1)H and (31)P), respectively, in aqueous buffer solutions at pH values of 5.0 and 7.4 and at temperatures of 25 and 37 °C. The hydrolytic degradation products of the PEVEP segments of the block copolymers were then identified by electrospray ionization, gas chromatography, and matrix-assisted laser desorption/ionization mass spectrometry. The parent micelles and their degradation products were found to be non-cytotoxic at concentrations up to 3 mg/mL, when evaluated with RAW 264.7 mouse macrophages and OVCAR-3 human ovarian adenocarcinoma cells.

No MeSH data available.


Related in: MedlinePlus