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Loading of Silica Nanoparticles in Block Copolymer Vesicles during Polymerization-Induced Self-Assembly: Encapsulation Efficiency and Thermally Triggered Release.

Mable CJ, Gibson RR, Prevost S, McKenzie BE, Mykhaylyk OO, Armes SP - J. Am. Chem. Soc. (2015)

Bottom Line: Silica has high electron contrast compared to the copolymer which facilitates TEM analysis, and its thermal stability enables quantification of the loading efficiency via thermogravimetric analysis.They may also serve as an active payload for self-healing hydrogels or repair of biological tissue.Finally, we also encapsulate a model globular protein, bovine serum albumin, and calculate its loading efficiency using fluorescence spectroscopy.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Sheffield , Brook Hill, Sheffield, South Yorkshire S3 7HF, United Kingdom.

ABSTRACT
Poly(glycerol monomethacrylate)-poly(2-hydroxypropyl methacrylate) diblock copolymer vesicles can be prepared in the form of concentrated aqueous dispersions via polymerization-induced self-assembly (PISA). In the present study, these syntheses are conducted in the presence of varying amounts of silica nanoparticles of approximately 18 nm diameter. This approach leads to encapsulation of up to hundreds of silica nanoparticles per vesicle. Silica has high electron contrast compared to the copolymer which facilitates TEM analysis, and its thermal stability enables quantification of the loading efficiency via thermogravimetric analysis. Encapsulation efficiencies can be calculated using disk centrifuge photosedimentometry, since the vesicle density increases at higher silica loadings while the mean vesicle diameter remains essentially unchanged. Small angle X-ray scattering (SAXS) is used to confirm silica encapsulation, since a structure factor is observed at q ≈ 0.25 nm(-1). A new two-population model provides satisfactory data fits to the SAXS patterns and allows the mean silica volume fraction within the vesicles to be determined. Finally, the thermoresponsive nature of the diblock copolymer vesicles enables thermally triggered release of the encapsulated silica nanoparticles simply by cooling to 0-10 °C, which induces a morphological transition. These silica-loaded vesicles constitute a useful model system for understanding the encapsulation of globular proteins, enzymes, or antibodies for potential biomedical applications. They may also serve as an active payload for self-healing hydrogels or repair of biological tissue. Finally, we also encapsulate a model globular protein, bovine serum albumin, and calculate its loading efficiency using fluorescence spectroscopy.

No MeSH data available.


Related in: MedlinePlus

SAXS patterns obtained for 1.0% w/w aqueous dispersionsof G58H250 diblock copolymer vesicles preparedvia PISAin the presence of varying amounts of silica nanoparticles (0%, 5%,and 35% w/w silica). Gray circles represent data, and solid linesrepresent fitting curves: when no silica was present during the vesiclesynthesis, a single-population vesicle model was sufficient to fitthe corresponding SAXS pattern, whereas two populations were requiredwhen silica nanoparticles were present during the PISA synthesis.Red and blue dashed lines represent populations 1 and 2, respectively.For clarity, the upper two SAXS patterns are shifted vertically byarbitrary scaling factors, as shown on the plot. (Inset) Schematicrepresentation of empty and silica-loaded G58H250 diblock copolymer vesicles, where small black circles representsilica nanoparticles, red = PGMA block (G), light blue = PHPMA block(H), Rm is the radius from the centerof the vesicle to the middle of the membrane, Tm is the membrane thickness, and Rg is the radius of gyration of the corona.
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fig6: SAXS patterns obtained for 1.0% w/w aqueous dispersionsof G58H250 diblock copolymer vesicles preparedvia PISAin the presence of varying amounts of silica nanoparticles (0%, 5%,and 35% w/w silica). Gray circles represent data, and solid linesrepresent fitting curves: when no silica was present during the vesiclesynthesis, a single-population vesicle model was sufficient to fitthe corresponding SAXS pattern, whereas two populations were requiredwhen silica nanoparticles were present during the PISA synthesis.Red and blue dashed lines represent populations 1 and 2, respectively.For clarity, the upper two SAXS patterns are shifted vertically byarbitrary scaling factors, as shown on the plot. (Inset) Schematicrepresentation of empty and silica-loaded G58H250 diblock copolymer vesicles, where small black circles representsilica nanoparticles, red = PGMA block (G), light blue = PHPMA block(H), Rm is the radius from the centerof the vesicle to the middle of the membrane, Tm is the membrane thickness, and Rg is the radius of gyration of the corona.

Mentions: However, this expression requiresmodificationto represent silica-loaded vesicles: the amplitudeof the membrane self-term in eq 2 must be replaced by an amplitude representing both the membraneand the silica-loaded lumen expressed as the form factor amplitudefor a core–shell spherical particle:463where Rin = Rm – (1/2)Tm is the radius of the lumen, Rout = Rm + (1/2)Tm is theouter radius of the membrane, Vin = (4/3)πRin3 is the volume of the vesiclelumen, and Vout = (4/3)πRout3 is the volume of the vesicle. Rm is the radius from the center of the vesicleto the middle of the membrane, Tm is themembrane thickness (Figure 6), and Φ(x) = (3[sin(x) – x cos(x)])/x3 is the form factor amplitude for a homogeneoussphere. The vesicle aggregation number (i.e., the mean number of copolymerchains per vesicle) is given by Nagg =(1 – xsol)(Vout – Vin)/Vm, where xsol is the solventfraction in the membrane and Vm is thevolume of the membrane-forming hydrophobic PHPMA block (Vm = VPHPMA250). The X-rayscattering length contrast for the corona block is βc = Vc(ξc – ξsol), where Vc is the corona blockvolume (VPGMA58). The block volumes arecalculated from V = Mw/(ρNA) using the weight-averagemolecular weight, Mw, of the block componentsand the mass densities of the three blocks comprising the copolymer(ρPHPMA = 1.21 ± 0.01 g cm–3 and ρPGMA = 1.31 ± 0.01 g cm–3; these values were determined for the corresponding homopolymersusing helium pycnometry). ξsol, ξm, ξc, and ξl are the X-ray scatteringlength densities of the surrounding solvent (ξH2O = 9.42 × 1010 cm–2), themembrane-forming hydrophobic block (ξPHPMA = 11.11× 1010 cm–2), the vesicle coronablock (ξPGMA = 11.94 × 1010 cm–2), and the vesicle lumen [ξl = (1 – VSiO2/Vin)ξH2O + (VSiO2/Vin)ξSiO2, where ξSiO2 = 17.5 × 1010 cm–2 and VSiO2 is the volume occupiedby silica nanoparticles within the lumen]. It should be mentionedthat the X-ray scattering length contrast for the membrane block isgiven by βm = Vm(ξm – ξsol). Thus the (βc/βm)2 ratio is approximately 0.08, whichsuggests that the profile of the electron density distribution withinthe corona should be included in the model. However, recent modelingof experimental data on a similar system has demonstrated that incorporationof a profile function in the model has a negligible effect on thederived structural parameters.38 The self-correlationterm for the corona block in eq 2 is given by the Debye function, Fc(qRg) = (2[exp(−q2Rg2) – 1 + q2Rg2])/(q4Rg4), where Rg is the radius of gyration of the corona block(Figure 6). Assumingthat there is no penetration of the corona blocks within the membrane,the amplitude of the corona self-term is expressed as:4where Ψ(qRg) = (1 – exp(−qRg))/(qRg)2 is the form factor amplitudeof the corona chain. The polydispersities for two parameters (Rm and Tm), expressedas a Gaussian distribution, are considered for the first (silica-loadedvesicle) population:5where σRm and σTm are the standard deviationsfor Rm and Tm, respectively. The number density per unit volume of population1 (l = 1 in eq 1) is expressed as:6where c1 is thetotal volume fraction of copolymer molecules formingvesicles in the sample and V1(r11, r12) is thetotal volume of copolymers in a vesicle [V1(r11, r12) = (Vm + Vc)Nagg(r11,r12)]. It is assumed that thevesicle dispersion is sufficiently dilute to enable the structurefactor for population 1 to be set to unity [S1(q) = 1]. Population 1 describes scatteringfrom a vesicle with a homogeneous lumen. However, the lumen actuallyhas a particulate structure arising from the encapsulated silica nanoparticles.This generates an additional scattering signal thatcan be described by population 2, for which l = 2in eq 1. The form factorfor this population is simply that for a homogeneous sphere:7where RSiO2 is the mean radius of the silica nanoparticles. All otherparameters and functions in the model for population 2 are analogousto those for population 1 (eq 2). The polydispersity of one parameter (RSiO2), expressed as a Gaussian distribution,is considered for population 2:8where σRSiO2 is the standard deviation for RSiO2. The number density per unit volume of population 2is expressed as:9where c2 is thetotal volume fraction of silica particles in thesample and V2(r21) = (4/3)πr213 is the volume of a singlespherical silica nanoparticle. Since interparticle interactions areexpected for silica particles occupying the vesicle lumen, a hard-sphereinteraction structure factor based on the Percus–Yevick approximation47 was introduced into the model for population2:10where RPY is theinteraction radius and fPY is an effectivehard-sphere volume fraction. The model was incorporated in Irena SASmacros for Igor Pro software,48 and numericalintegration of eqs 1,6, and 9 was used fordata fitting.


Loading of Silica Nanoparticles in Block Copolymer Vesicles during Polymerization-Induced Self-Assembly: Encapsulation Efficiency and Thermally Triggered Release.

Mable CJ, Gibson RR, Prevost S, McKenzie BE, Mykhaylyk OO, Armes SP - J. Am. Chem. Soc. (2015)

SAXS patterns obtained for 1.0% w/w aqueous dispersionsof G58H250 diblock copolymer vesicles preparedvia PISAin the presence of varying amounts of silica nanoparticles (0%, 5%,and 35% w/w silica). Gray circles represent data, and solid linesrepresent fitting curves: when no silica was present during the vesiclesynthesis, a single-population vesicle model was sufficient to fitthe corresponding SAXS pattern, whereas two populations were requiredwhen silica nanoparticles were present during the PISA synthesis.Red and blue dashed lines represent populations 1 and 2, respectively.For clarity, the upper two SAXS patterns are shifted vertically byarbitrary scaling factors, as shown on the plot. (Inset) Schematicrepresentation of empty and silica-loaded G58H250 diblock copolymer vesicles, where small black circles representsilica nanoparticles, red = PGMA block (G), light blue = PHPMA block(H), Rm is the radius from the centerof the vesicle to the middle of the membrane, Tm is the membrane thickness, and Rg is the radius of gyration of the corona.
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fig6: SAXS patterns obtained for 1.0% w/w aqueous dispersionsof G58H250 diblock copolymer vesicles preparedvia PISAin the presence of varying amounts of silica nanoparticles (0%, 5%,and 35% w/w silica). Gray circles represent data, and solid linesrepresent fitting curves: when no silica was present during the vesiclesynthesis, a single-population vesicle model was sufficient to fitthe corresponding SAXS pattern, whereas two populations were requiredwhen silica nanoparticles were present during the PISA synthesis.Red and blue dashed lines represent populations 1 and 2, respectively.For clarity, the upper two SAXS patterns are shifted vertically byarbitrary scaling factors, as shown on the plot. (Inset) Schematicrepresentation of empty and silica-loaded G58H250 diblock copolymer vesicles, where small black circles representsilica nanoparticles, red = PGMA block (G), light blue = PHPMA block(H), Rm is the radius from the centerof the vesicle to the middle of the membrane, Tm is the membrane thickness, and Rg is the radius of gyration of the corona.
Mentions: However, this expression requiresmodificationto represent silica-loaded vesicles: the amplitudeof the membrane self-term in eq 2 must be replaced by an amplitude representing both the membraneand the silica-loaded lumen expressed as the form factor amplitudefor a core–shell spherical particle:463where Rin = Rm – (1/2)Tm is the radius of the lumen, Rout = Rm + (1/2)Tm is theouter radius of the membrane, Vin = (4/3)πRin3 is the volume of the vesiclelumen, and Vout = (4/3)πRout3 is the volume of the vesicle. Rm is the radius from the center of the vesicleto the middle of the membrane, Tm is themembrane thickness (Figure 6), and Φ(x) = (3[sin(x) – x cos(x)])/x3 is the form factor amplitude for a homogeneoussphere. The vesicle aggregation number (i.e., the mean number of copolymerchains per vesicle) is given by Nagg =(1 – xsol)(Vout – Vin)/Vm, where xsol is the solventfraction in the membrane and Vm is thevolume of the membrane-forming hydrophobic PHPMA block (Vm = VPHPMA250). The X-rayscattering length contrast for the corona block is βc = Vc(ξc – ξsol), where Vc is the corona blockvolume (VPGMA58). The block volumes arecalculated from V = Mw/(ρNA) using the weight-averagemolecular weight, Mw, of the block componentsand the mass densities of the three blocks comprising the copolymer(ρPHPMA = 1.21 ± 0.01 g cm–3 and ρPGMA = 1.31 ± 0.01 g cm–3; these values were determined for the corresponding homopolymersusing helium pycnometry). ξsol, ξm, ξc, and ξl are the X-ray scatteringlength densities of the surrounding solvent (ξH2O = 9.42 × 1010 cm–2), themembrane-forming hydrophobic block (ξPHPMA = 11.11× 1010 cm–2), the vesicle coronablock (ξPGMA = 11.94 × 1010 cm–2), and the vesicle lumen [ξl = (1 – VSiO2/Vin)ξH2O + (VSiO2/Vin)ξSiO2, where ξSiO2 = 17.5 × 1010 cm–2 and VSiO2 is the volume occupiedby silica nanoparticles within the lumen]. It should be mentionedthat the X-ray scattering length contrast for the membrane block isgiven by βm = Vm(ξm – ξsol). Thus the (βc/βm)2 ratio is approximately 0.08, whichsuggests that the profile of the electron density distribution withinthe corona should be included in the model. However, recent modelingof experimental data on a similar system has demonstrated that incorporationof a profile function in the model has a negligible effect on thederived structural parameters.38 The self-correlationterm for the corona block in eq 2 is given by the Debye function, Fc(qRg) = (2[exp(−q2Rg2) – 1 + q2Rg2])/(q4Rg4), where Rg is the radius of gyration of the corona block(Figure 6). Assumingthat there is no penetration of the corona blocks within the membrane,the amplitude of the corona self-term is expressed as:4where Ψ(qRg) = (1 – exp(−qRg))/(qRg)2 is the form factor amplitudeof the corona chain. The polydispersities for two parameters (Rm and Tm), expressedas a Gaussian distribution, are considered for the first (silica-loadedvesicle) population:5where σRm and σTm are the standard deviationsfor Rm and Tm, respectively. The number density per unit volume of population1 (l = 1 in eq 1) is expressed as:6where c1 is thetotal volume fraction of copolymer molecules formingvesicles in the sample and V1(r11, r12) is thetotal volume of copolymers in a vesicle [V1(r11, r12) = (Vm + Vc)Nagg(r11,r12)]. It is assumed that thevesicle dispersion is sufficiently dilute to enable the structurefactor for population 1 to be set to unity [S1(q) = 1]. Population 1 describes scatteringfrom a vesicle with a homogeneous lumen. However, the lumen actuallyhas a particulate structure arising from the encapsulated silica nanoparticles.This generates an additional scattering signal thatcan be described by population 2, for which l = 2in eq 1. The form factorfor this population is simply that for a homogeneous sphere:7where RSiO2 is the mean radius of the silica nanoparticles. All otherparameters and functions in the model for population 2 are analogousto those for population 1 (eq 2). The polydispersity of one parameter (RSiO2), expressed as a Gaussian distribution,is considered for population 2:8where σRSiO2 is the standard deviation for RSiO2. The number density per unit volume of population 2is expressed as:9where c2 is thetotal volume fraction of silica particles in thesample and V2(r21) = (4/3)πr213 is the volume of a singlespherical silica nanoparticle. Since interparticle interactions areexpected for silica particles occupying the vesicle lumen, a hard-sphereinteraction structure factor based on the Percus–Yevick approximation47 was introduced into the model for population2:10where RPY is theinteraction radius and fPY is an effectivehard-sphere volume fraction. The model was incorporated in Irena SASmacros for Igor Pro software,48 and numericalintegration of eqs 1,6, and 9 was used fordata fitting.

Bottom Line: Silica has high electron contrast compared to the copolymer which facilitates TEM analysis, and its thermal stability enables quantification of the loading efficiency via thermogravimetric analysis.They may also serve as an active payload for self-healing hydrogels or repair of biological tissue.Finally, we also encapsulate a model globular protein, bovine serum albumin, and calculate its loading efficiency using fluorescence spectroscopy.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Sheffield , Brook Hill, Sheffield, South Yorkshire S3 7HF, United Kingdom.

ABSTRACT
Poly(glycerol monomethacrylate)-poly(2-hydroxypropyl methacrylate) diblock copolymer vesicles can be prepared in the form of concentrated aqueous dispersions via polymerization-induced self-assembly (PISA). In the present study, these syntheses are conducted in the presence of varying amounts of silica nanoparticles of approximately 18 nm diameter. This approach leads to encapsulation of up to hundreds of silica nanoparticles per vesicle. Silica has high electron contrast compared to the copolymer which facilitates TEM analysis, and its thermal stability enables quantification of the loading efficiency via thermogravimetric analysis. Encapsulation efficiencies can be calculated using disk centrifuge photosedimentometry, since the vesicle density increases at higher silica loadings while the mean vesicle diameter remains essentially unchanged. Small angle X-ray scattering (SAXS) is used to confirm silica encapsulation, since a structure factor is observed at q ≈ 0.25 nm(-1). A new two-population model provides satisfactory data fits to the SAXS patterns and allows the mean silica volume fraction within the vesicles to be determined. Finally, the thermoresponsive nature of the diblock copolymer vesicles enables thermally triggered release of the encapsulated silica nanoparticles simply by cooling to 0-10 °C, which induces a morphological transition. These silica-loaded vesicles constitute a useful model system for understanding the encapsulation of globular proteins, enzymes, or antibodies for potential biomedical applications. They may also serve as an active payload for self-healing hydrogels or repair of biological tissue. Finally, we also encapsulate a model globular protein, bovine serum albumin, and calculate its loading efficiency using fluorescence spectroscopy.

No MeSH data available.


Related in: MedlinePlus