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

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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.

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Abbreviations

ζ-potential:

Electrokinetic potential

η :

Shear viscosity

θ :

Scattering angle

λ :

Wavelength

ν :

Wavenumber

τ :

Time

τ fast :

Fast relaxation time

τ slow :

Slow relaxation time

A :

Absorbance

A 2 :

Virial coefficient

A fast :

Portion of scattered light relating in fast mode

A slow :

Portion of scattered light relating in slow mode

AGU:

Anhydrous glucose unit

C :

Concentration

C Ptx,0 :

Concentration of paclitaxel at the start of loading

C Ptx, τ :

Concentration of paclitaxel at the τ moment

C Na-CMC- g-PVI :

Concentration of synthesized copolymer

CMC:

Carboxymethyl cellulose

EE:

Encapsulation efficiency

FG:

Frequency of grafting

K :

Solution optical constant

k 0 :

Zero-order release rate constant

LE:

Loading efficiency

m PVI g :

Mass of grafted PVI calculated from FTIR data

m PVI 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

q 0 :

Initial level of the drug in the media

q τ :

Level of the released drug in time τ

q ∞ :

Equilibrium level of the released drug

R θ :

Scattering coefficient at the θ scattering angle

R h :

Hydrodynamic radius

R fasth :

Hydrodynamic radius in fast mode

R slowh :

Hydrodynamic radius in slow mode

R g :

Radius of gyration

R fastg :

Radius of gyration in fast mode

R slowg :

Radius of gyration in slow mode

T :

Absolute temperature

VI:

N-Vinylimidazole

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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.

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Authors and Affiliations

  1. Polymer Science and Colloid Chemistry Department, Voronezh State University, Voronezh, Russia

    Vyacheslav A. Kuznetsov, Andrey V. Sorokin, Maria S. Lavlinskaya & Dmitriy V. Bykovskiy

  2. Center of Collective Use of Scientific Equipment, Voronezh State University, Voronezh, Russia

    Alexander A. Sinelnikov

Authors
  1. Vyacheslav A. Kuznetsov
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  2. Andrey V. Sorokin
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  3. Maria S. Lavlinskaya
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  4. Alexander A. Sinelnikov
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Correspondence to Vyacheslav A. Kuznetsov.

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Kuznetsov, V.A., Sorokin, A.V., Lavlinskaya, M.S. et al. Graft copolymers of carboxymethyl cellulose with N-vinylimidazole: synthesis and application for drug delivery. Polym. Bull. 76, 4929–4949 (2019). https://doi.org/10.1007/s00289-018-2635-0

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  • DOI: https://doi.org/10.1007/s00289-018-2635-0

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