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Graft copolymers of carboxymethyl cellulose with N-vinylimidazole: synthesis and application for drug delivery

  • Vyacheslav A. Kuznetsov
  • Andrey V. Sorokin
  • Maria S. Lavlinskaya
  • Alexander A. Sinelnikov
  • Dmitriy V. Bykovskiy
Original Paper
  • 16 Downloads

Abstract

Graft copolymers of sodium salt of carboxymethyl cellulose and N-vinylimidazole with different contents of the latter are synthesized by radical polymerization. Polymerization kinetics for all samples is researched by copolymer composition determination by UV spectroscopy, and it was found that it lasted 180 min. Percent of grafting calculated from FTIR data is in the range 31–59%, which correlated with GPC and static light scattering data. Aqueous solutions of the synthesized copolymers are characterized by dynamic light scattering (DLS), transmission electron microscopy, and zeta potential measurement. It was established that macromolecular particles of all synthesized copolymers possess non-spherical shape and negative electrokinetic potential value. The hydrodynamic radii of the polymer coils are 120–152 nm. It was found by DLS that macromolecular coils of all copolymers are stable in 0.15 M NaCl aqueous solution and in the physiological pH range which allows to apply them as vectors for targeted drug delivery. Interaction between paclitaxel (Ptx) and Na-CMC-g-PVI copolymer was studied by UV spectroscopy, FTIR, and TEM. Copolymer and Ptx complex formation proceeds by interaction of imidazole cycles and methylene backbone of Na-CMC-g-PVI copolymer and C=O groups and aromatic rings of Ptx. In vitro release kinetics was also researched in acidic and neutral media at 38 °C. Particularly, full release of paclitaxel is reached after 144 h. Release process of Ptx from copolymer particles is described by Korsmeyer–Peppas kinetic model and limited by molecular diffusion.

Keywords

Graft copolymers Carboxymethyl cellulose N-Vinylimidazole Biocompatible polymers Paclitaxel Release kinetics 

List of symbols

ζ-potential

Electrokinetic potential

η

Shear viscosity

θ

Scattering angle

λ

Wavelength

ν

Wavenumber

τ

Time

τfast

Fast relaxation time

τslow

Slow relaxation time

A

Absorbance

A2

Virial coefficient

Afast

Portion of scattered light relating in fast mode

Aslow

Portion of scattered light relating in slow mode

AGU

Anhydrous glucose unit

C

Concentration

CPtx,0

Concentration of paclitaxel at the start of loading

CPtx, τ

Concentration of paclitaxel at the τ moment

CNa-CMC- g-PVI

Concentration of synthesized copolymer

CMC

Carboxymethyl cellulose

EE

Encapsulation efficiency

FG

Frequency of grafting

K

Solution optical constant

k0

Zero-order release rate constant

LE

Loading efficiency

mPVI g

Mass of grafted PVI calculated from FTIR data

mPVI t

Theoretical mass of PVI

n

Diffusional exponent

Na-CMC

Sodium salt of carboxymethyl cellulose

Na-CMC-g-PVI

Graft copolymer of CMC and N-vinylimidazole

PG

Percent of grafting

Ptx

Paclitaxel

PVI

Poly-N-vinylimidazole

q

Wave vector modulus

q0

Initial level of the drug in the media

qτ

Level of the released drug in time τ

q

Equilibrium level of the released drug

Rθ

Scattering coefficient at the θ scattering angle

Rh

Hydrodynamic radius

Rhfast

Hydrodynamic radius in fast mode

Rhslow

Hydrodynamic radius in slow mode

Rg

Radius of gyration

Rgfast

Radius of gyration in fast mode

Rgslow

Radius of gyration in slow mode

T

Absolute temperature

VI

N-Vinylimidazole

Notes

Acknowledgements

FTIR, TEM, UV, zeta potential data were obtained with the use of equipment of Centre of Collective Usage of Scientific Equipment of Voronezh State University.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Vyacheslav A. Kuznetsov
    • 1
  • Andrey V. Sorokin
    • 1
  • Maria S. Lavlinskaya
    • 1
  • Alexander A. Sinelnikov
    • 2
  • Dmitriy V. Bykovskiy
    • 1
  1. 1.Polymer Science and Colloid Chemistry DepartmentVoronezh State UniversityVoronezhRussia
  2. 2.Center of Collective Use of Scientific EquipmentVoronezh State UniversityVoronezhRussia

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