Effect of formulation and processing parameters on the size of mPEG-b-p(HPMA-Bz) polymeric micelles

Mahsa Bagheri, Jaleesa Bresseleers, Aida Varela-Moreira, Olivier Sandre, Silvie A. Meeuwissen, Raymond M. Schiffelers, Josbert M. Metselaar, Cornelus F. Van Nostrum, Jan C.M. van Hest, Wim E. Hennink

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)

Abstract

Micelles composed of block copolymers of poly(ethylene glycol)-b-poly(N-2-benzoyloxypropyl methacrylamide) (mPEG-b-p(HPMA-Bz)) have shown great promise as drug-delivery carriers due to their excellent stability and high loading capacity. In the present study, parameters influencing micelle size were investigated to tailor sizes in the range of 25-100 nm. Micelles were prepared by a nanoprecipitation method, and their size was modulated by the block copolymer properties such as molecular weight, their hydrophilic-to-hydrophobic ratio, homopolymer content, as well as formulation and processing parameters. It was shown that the micelles have a core-shell structure using a combination of dynamic light scattering and transmission electron microscopy analysis. By varying the degree of polymerization of the hydrophobic block (NB) between 68 and 10, at a fixed hydrophilic block mPEG5k (NA = 114), it was shown that the hydrophobic core of the micelle was collapsed following the power law of (NB × Nagg)1/3. Further, the calculated brush height was similar for all the micelles examined (10 nm), indicating that crew-cut micelles were made. Both addition of homopolymer and preparation of micelles at lower concentrations or lower rates of addition of the organic solvent to the aqueous phase increased the size of micelles due to partitioning of the hydrophobic homopolymer chains to the core of the micelles and lower nucleation rates, respectively. Furthermore, it was shown that by using different solvents, the size of the micelles substantially changed. The use of acetone, acetonitrile, ethanol, tetrahydrofuran, and dioxane resulted in micelles in the size range of 45-60 nm after removal of the organic solvents. The use of dimethylformamide and dimethylsulfoxide led to markedly larger sizes of 75 and 180 nm, respectively. In conclusion, the results show that by modulating polymer properties and processing conditions, micelles with tailorable sizes can be obtained.

LanguageEnglish
Pages15495-15506
JournalLangmuir
Volume34
Issue number50
DOIs
StatePublished - 12 Nov 2018

Fingerprint

hydroxypropyl methacrylate
Micelles
micelles
formulations
Processing
Homopolymerization
block copolymers
Organic solvents
Block copolymers

Cite this

Bagheri, M., Bresseleers, J., Varela-Moreira, A., Sandre, O., Meeuwissen, S. A., Schiffelers, R. M., ... Hennink, W. E. (2018). Effect of formulation and processing parameters on the size of mPEG-b-p(HPMA-Bz) polymeric micelles. Langmuir, 34(50), 15495-15506. DOI: 10.1021/acs.langmuir.8b03576
Bagheri, Mahsa ; Bresseleers, Jaleesa ; Varela-Moreira, Aida ; Sandre, Olivier ; Meeuwissen, Silvie A. ; Schiffelers, Raymond M. ; Metselaar, Josbert M. ; Van Nostrum, Cornelus F. ; van Hest, Jan C.M. ; Hennink, Wim E./ Effect of formulation and processing parameters on the size of mPEG-b-p(HPMA-Bz) polymeric micelles. In: Langmuir. 2018 ; Vol. 34, No. 50. pp. 15495-15506
@article{6a513e829f7d4b0aa5f6daf96a7965ff,
title = "Effect of formulation and processing parameters on the size of mPEG-b-p(HPMA-Bz) polymeric micelles",
abstract = "Micelles composed of block copolymers of poly(ethylene glycol)-b-poly(N-2-benzoyloxypropyl methacrylamide) (mPEG-b-p(HPMA-Bz)) have shown great promise as drug-delivery carriers due to their excellent stability and high loading capacity. In the present study, parameters influencing micelle size were investigated to tailor sizes in the range of 25-100 nm. Micelles were prepared by a nanoprecipitation method, and their size was modulated by the block copolymer properties such as molecular weight, their hydrophilic-to-hydrophobic ratio, homopolymer content, as well as formulation and processing parameters. It was shown that the micelles have a core-shell structure using a combination of dynamic light scattering and transmission electron microscopy analysis. By varying the degree of polymerization of the hydrophobic block (NB) between 68 and 10, at a fixed hydrophilic block mPEG5k (NA = 114), it was shown that the hydrophobic core of the micelle was collapsed following the power law of (NB × Nagg)1/3. Further, the calculated brush height was similar for all the micelles examined (10 nm), indicating that crew-cut micelles were made. Both addition of homopolymer and preparation of micelles at lower concentrations or lower rates of addition of the organic solvent to the aqueous phase increased the size of micelles due to partitioning of the hydrophobic homopolymer chains to the core of the micelles and lower nucleation rates, respectively. Furthermore, it was shown that by using different solvents, the size of the micelles substantially changed. The use of acetone, acetonitrile, ethanol, tetrahydrofuran, and dioxane resulted in micelles in the size range of 45-60 nm after removal of the organic solvents. The use of dimethylformamide and dimethylsulfoxide led to markedly larger sizes of 75 and 180 nm, respectively. In conclusion, the results show that by modulating polymer properties and processing conditions, micelles with tailorable sizes can be obtained.",
author = "Mahsa Bagheri and Jaleesa Bresseleers and Aida Varela-Moreira and Olivier Sandre and Meeuwissen, {Silvie A.} and Schiffelers, {Raymond M.} and Metselaar, {Josbert M.} and {Van Nostrum}, {Cornelus F.} and {van Hest}, {Jan C.M.} and Hennink, {Wim E.}",
year = "2018",
month = "11",
day = "12",
doi = "10.1021/acs.langmuir.8b03576",
language = "English",
volume = "34",
pages = "15495--15506",
journal = "Langmuir",
issn = "0743-7463",
publisher = "American Chemical Society",
number = "50",

}

Bagheri, M, Bresseleers, J, Varela-Moreira, A, Sandre, O, Meeuwissen, SA, Schiffelers, RM, Metselaar, JM, Van Nostrum, CF, van Hest, JCM & Hennink, WE 2018, 'Effect of formulation and processing parameters on the size of mPEG-b-p(HPMA-Bz) polymeric micelles' Langmuir, vol. 34, no. 50, pp. 15495-15506. DOI: 10.1021/acs.langmuir.8b03576

Effect of formulation and processing parameters on the size of mPEG-b-p(HPMA-Bz) polymeric micelles. / Bagheri, Mahsa; Bresseleers, Jaleesa; Varela-Moreira, Aida; Sandre, Olivier; Meeuwissen, Silvie A.; Schiffelers, Raymond M.; Metselaar, Josbert M.; Van Nostrum, Cornelus F.; van Hest, Jan C.M.; Hennink, Wim E.

In: Langmuir, Vol. 34, No. 50, 12.11.2018, p. 15495-15506.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Effect of formulation and processing parameters on the size of mPEG-b-p(HPMA-Bz) polymeric micelles

AU - Bagheri,Mahsa

AU - Bresseleers,Jaleesa

AU - Varela-Moreira,Aida

AU - Sandre,Olivier

AU - Meeuwissen,Silvie A.

AU - Schiffelers,Raymond M.

AU - Metselaar,Josbert M.

AU - Van Nostrum,Cornelus F.

AU - van Hest,Jan C.M.

AU - Hennink,Wim E.

PY - 2018/11/12

Y1 - 2018/11/12

N2 - Micelles composed of block copolymers of poly(ethylene glycol)-b-poly(N-2-benzoyloxypropyl methacrylamide) (mPEG-b-p(HPMA-Bz)) have shown great promise as drug-delivery carriers due to their excellent stability and high loading capacity. In the present study, parameters influencing micelle size were investigated to tailor sizes in the range of 25-100 nm. Micelles were prepared by a nanoprecipitation method, and their size was modulated by the block copolymer properties such as molecular weight, their hydrophilic-to-hydrophobic ratio, homopolymer content, as well as formulation and processing parameters. It was shown that the micelles have a core-shell structure using a combination of dynamic light scattering and transmission electron microscopy analysis. By varying the degree of polymerization of the hydrophobic block (NB) between 68 and 10, at a fixed hydrophilic block mPEG5k (NA = 114), it was shown that the hydrophobic core of the micelle was collapsed following the power law of (NB × Nagg)1/3. Further, the calculated brush height was similar for all the micelles examined (10 nm), indicating that crew-cut micelles were made. Both addition of homopolymer and preparation of micelles at lower concentrations or lower rates of addition of the organic solvent to the aqueous phase increased the size of micelles due to partitioning of the hydrophobic homopolymer chains to the core of the micelles and lower nucleation rates, respectively. Furthermore, it was shown that by using different solvents, the size of the micelles substantially changed. The use of acetone, acetonitrile, ethanol, tetrahydrofuran, and dioxane resulted in micelles in the size range of 45-60 nm after removal of the organic solvents. The use of dimethylformamide and dimethylsulfoxide led to markedly larger sizes of 75 and 180 nm, respectively. In conclusion, the results show that by modulating polymer properties and processing conditions, micelles with tailorable sizes can be obtained.

AB - Micelles composed of block copolymers of poly(ethylene glycol)-b-poly(N-2-benzoyloxypropyl methacrylamide) (mPEG-b-p(HPMA-Bz)) have shown great promise as drug-delivery carriers due to their excellent stability and high loading capacity. In the present study, parameters influencing micelle size were investigated to tailor sizes in the range of 25-100 nm. Micelles were prepared by a nanoprecipitation method, and their size was modulated by the block copolymer properties such as molecular weight, their hydrophilic-to-hydrophobic ratio, homopolymer content, as well as formulation and processing parameters. It was shown that the micelles have a core-shell structure using a combination of dynamic light scattering and transmission electron microscopy analysis. By varying the degree of polymerization of the hydrophobic block (NB) between 68 and 10, at a fixed hydrophilic block mPEG5k (NA = 114), it was shown that the hydrophobic core of the micelle was collapsed following the power law of (NB × Nagg)1/3. Further, the calculated brush height was similar for all the micelles examined (10 nm), indicating that crew-cut micelles were made. Both addition of homopolymer and preparation of micelles at lower concentrations or lower rates of addition of the organic solvent to the aqueous phase increased the size of micelles due to partitioning of the hydrophobic homopolymer chains to the core of the micelles and lower nucleation rates, respectively. Furthermore, it was shown that by using different solvents, the size of the micelles substantially changed. The use of acetone, acetonitrile, ethanol, tetrahydrofuran, and dioxane resulted in micelles in the size range of 45-60 nm after removal of the organic solvents. The use of dimethylformamide and dimethylsulfoxide led to markedly larger sizes of 75 and 180 nm, respectively. In conclusion, the results show that by modulating polymer properties and processing conditions, micelles with tailorable sizes can be obtained.

UR - http://www.scopus.com/inward/record.url?scp=85057562103&partnerID=8YFLogxK

U2 - 10.1021/acs.langmuir.8b03576

DO - 10.1021/acs.langmuir.8b03576

M3 - Article

VL - 34

SP - 15495

EP - 15506

JO - Langmuir

T2 - Langmuir

JF - Langmuir

SN - 0743-7463

IS - 50

ER -

Bagheri M, Bresseleers J, Varela-Moreira A, Sandre O, Meeuwissen SA, Schiffelers RM et al. Effect of formulation and processing parameters on the size of mPEG-b-p(HPMA-Bz) polymeric micelles. Langmuir. 2018 Nov 12;34(50):15495-15506. Available from, DOI: 10.1021/acs.langmuir.8b03576