Redox-responsive degradable prodrug nanogels for intracellular drug delivery by crosslinking of amine-functionalized poly(N-vinylpyrrolidone) copolymers

Huan Peng, Xiaobin Huang, Andrea Melle, Marcel Karperien, Andrij Pich (Corresponding Author)

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Scopus)

Abstract

Hypothesis: Facile approaches for the development of new tailored drug carriers are of high importance for the controlled administration of drugs. Herein we report a method for the synthesis of water-soluble reactive copolymers with well-defined architectures for fabrication of redox-sensitive degradable prodrug nanogels for intracellular drug release. Experiments: Primary amine-functionalized statistical copolymers were obtained by hydrolysis of poly(N-vinylpyrrolidone-co-N-vinylformamide) copolymers which were synthesized via Reversible Addition–Fragmentation chain-Transfer (RAFT) polymerization. Redox-sensitive degradable nanogels with varying crosslinking densities were synthesized with a redox-sensitive cross-linker. Doxorubicin (DOX) was loaded to form prodrug nanogels (DNG) with hydrodynamic radius from 142 nm to 240 nm. Findings: The nanogels demonstrated slower degradation and retarded drug release rate with increased crosslinking density in the presence of 10 mM reduced glutathione (GSH) at 37 °C. The in vitro release studies revealed that maximum 85% DOX was released in 24 h under a reductive environment. Intracellular drug release profiles in HeLa cells indicated that the DOX delivery rate was tunable via varying crosslinking density of the nanogels. Cell viability assay demonstrated that the blank nanogels were biocompatible in wide concentrations up to 0.5 mg/mL while the DOX-loaded nanogels displayed medium antitumor activity with IC50 (half-maximal inhibitory concentration) of 1.80 μg/mL, 2.57 μg/mL, 3.01 μg/mL for DNG5, DNG10 and DNG15 respectively.

Original languageEnglish
Pages (from-to)612-622
Number of pages11
JournalJournal of colloid and interface science
Volume540
DOIs
Publication statusPublished - 22 Mar 2019

Fingerprint

Prodrugs
Drug delivery
Crosslinking
Amines
Copolymers
Doxorubicin
Hydrolysis
Assays
Pharmaceutical Preparations
Hydrodynamics
Polymerization
Cells
Fabrication
Degradation
Drug Carriers
Oxidation-Reduction
NanoGel
N-vinyl-2-pyrrolidinone
Water
Glutathione

Keywords

  • Degradable
  • Drug delivery
  • Nanogel
  • Prodrug
  • Redox-responsive
  • Tunable crosslinking density

Cite this

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title = "Redox-responsive degradable prodrug nanogels for intracellular drug delivery by crosslinking of amine-functionalized poly(N-vinylpyrrolidone) copolymers",
abstract = "Hypothesis: Facile approaches for the development of new tailored drug carriers are of high importance for the controlled administration of drugs. Herein we report a method for the synthesis of water-soluble reactive copolymers with well-defined architectures for fabrication of redox-sensitive degradable prodrug nanogels for intracellular drug release. Experiments: Primary amine-functionalized statistical copolymers were obtained by hydrolysis of poly(N-vinylpyrrolidone-co-N-vinylformamide) copolymers which were synthesized via Reversible Addition–Fragmentation chain-Transfer (RAFT) polymerization. Redox-sensitive degradable nanogels with varying crosslinking densities were synthesized with a redox-sensitive cross-linker. Doxorubicin (DOX) was loaded to form prodrug nanogels (DNG) with hydrodynamic radius from 142 nm to 240 nm. Findings: The nanogels demonstrated slower degradation and retarded drug release rate with increased crosslinking density in the presence of 10 mM reduced glutathione (GSH) at 37 °C. The in vitro release studies revealed that maximum 85{\%} DOX was released in 24 h under a reductive environment. Intracellular drug release profiles in HeLa cells indicated that the DOX delivery rate was tunable via varying crosslinking density of the nanogels. Cell viability assay demonstrated that the blank nanogels were biocompatible in wide concentrations up to 0.5 mg/mL while the DOX-loaded nanogels displayed medium antitumor activity with IC50 (half-maximal inhibitory concentration) of 1.80 μg/mL, 2.57 μg/mL, 3.01 μg/mL for DNG5, DNG10 and DNG15 respectively.",
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author = "Huan Peng and Xiaobin Huang and Andrea Melle and Marcel Karperien and Andrij Pich",
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Redox-responsive degradable prodrug nanogels for intracellular drug delivery by crosslinking of amine-functionalized poly(N-vinylpyrrolidone) copolymers. / Peng, Huan; Huang, Xiaobin; Melle, Andrea; Karperien, Marcel; Pich, Andrij (Corresponding Author).

In: Journal of colloid and interface science, Vol. 540, 22.03.2019, p. 612-622.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Redox-responsive degradable prodrug nanogels for intracellular drug delivery by crosslinking of amine-functionalized poly(N-vinylpyrrolidone) copolymers

AU - Peng, Huan

AU - Huang, Xiaobin

AU - Melle, Andrea

AU - Karperien, Marcel

AU - Pich, Andrij

PY - 2019/3/22

Y1 - 2019/3/22

N2 - Hypothesis: Facile approaches for the development of new tailored drug carriers are of high importance for the controlled administration of drugs. Herein we report a method for the synthesis of water-soluble reactive copolymers with well-defined architectures for fabrication of redox-sensitive degradable prodrug nanogels for intracellular drug release. Experiments: Primary amine-functionalized statistical copolymers were obtained by hydrolysis of poly(N-vinylpyrrolidone-co-N-vinylformamide) copolymers which were synthesized via Reversible Addition–Fragmentation chain-Transfer (RAFT) polymerization. Redox-sensitive degradable nanogels with varying crosslinking densities were synthesized with a redox-sensitive cross-linker. Doxorubicin (DOX) was loaded to form prodrug nanogels (DNG) with hydrodynamic radius from 142 nm to 240 nm. Findings: The nanogels demonstrated slower degradation and retarded drug release rate with increased crosslinking density in the presence of 10 mM reduced glutathione (GSH) at 37 °C. The in vitro release studies revealed that maximum 85% DOX was released in 24 h under a reductive environment. Intracellular drug release profiles in HeLa cells indicated that the DOX delivery rate was tunable via varying crosslinking density of the nanogels. Cell viability assay demonstrated that the blank nanogels were biocompatible in wide concentrations up to 0.5 mg/mL while the DOX-loaded nanogels displayed medium antitumor activity with IC50 (half-maximal inhibitory concentration) of 1.80 μg/mL, 2.57 μg/mL, 3.01 μg/mL for DNG5, DNG10 and DNG15 respectively.

AB - Hypothesis: Facile approaches for the development of new tailored drug carriers are of high importance for the controlled administration of drugs. Herein we report a method for the synthesis of water-soluble reactive copolymers with well-defined architectures for fabrication of redox-sensitive degradable prodrug nanogels for intracellular drug release. Experiments: Primary amine-functionalized statistical copolymers were obtained by hydrolysis of poly(N-vinylpyrrolidone-co-N-vinylformamide) copolymers which were synthesized via Reversible Addition–Fragmentation chain-Transfer (RAFT) polymerization. Redox-sensitive degradable nanogels with varying crosslinking densities were synthesized with a redox-sensitive cross-linker. Doxorubicin (DOX) was loaded to form prodrug nanogels (DNG) with hydrodynamic radius from 142 nm to 240 nm. Findings: The nanogels demonstrated slower degradation and retarded drug release rate with increased crosslinking density in the presence of 10 mM reduced glutathione (GSH) at 37 °C. The in vitro release studies revealed that maximum 85% DOX was released in 24 h under a reductive environment. Intracellular drug release profiles in HeLa cells indicated that the DOX delivery rate was tunable via varying crosslinking density of the nanogels. Cell viability assay demonstrated that the blank nanogels were biocompatible in wide concentrations up to 0.5 mg/mL while the DOX-loaded nanogels displayed medium antitumor activity with IC50 (half-maximal inhibitory concentration) of 1.80 μg/mL, 2.57 μg/mL, 3.01 μg/mL for DNG5, DNG10 and DNG15 respectively.

KW - Degradable

KW - Drug delivery

KW - Nanogel

KW - Prodrug

KW - Redox-responsive

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U2 - 10.1016/j.jcis.2019.01.049

DO - 10.1016/j.jcis.2019.01.049

M3 - Article

VL - 540

SP - 612

EP - 622

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JF - Journal of colloid and interface science

SN - 0021-9797

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