Functional derivatives of chitosan, soluble in neutral medium as drugs and genetic material carrier: preparation and properties

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Abstract

Method of chitosan modification, providing controlled addition of the quaternized block has been proposed. The structure of the products obtained were studied by FT-IR and NMR spectroscopy; their solubility and acid-base properties was characterized by turbodimetry and potentiometry, respectively. Presence about 50% of quaternized amino groups was shown to be necessary to obtain soluble products. The difference in pH-sensitivity of modified derivatives with different types of quaternized block attachment was revealed by studying their interaction with a model polystyrene sulfonate anion. The possibility of preparing complexes based on the obtained derivatives with DNA — polyplexes, stable under conditions close to physiological ones has been demonstrated. It was shown the presence of primary amino groups on the polycation chains leads to a decrease in the polyplexe size. The data obtained can form the basis for development of drug and genetic material delivery system.

The 2-stage method of chitosan modification providing controlled addition of the quaternized block has been proposed. The structure of the products obtained were studied by FT-IR and NMR spectroscopy; their solubility and acid-base properties was characterized by turbodimetry and potentiometry, respectively. The presence about 50% of quaternized amino groups was shown to be necessary to obtain soluble products. The difference in pH-sensitivity of modified derivatives with different types of quaternized block attachment was revealed by studying their interaction with a model polystyrene sulfonate anion. The possibility of preparing complexes based on the obtained derivatives with DNA, polyplexes stable under conditions close to physiological ones has been demonstrated. It is shown that the presence of primary amino groups on the polycation chains leads to a decrease in the polyplexe size. The data obtained can form the basis for development of drug and genetic material delivery systems.

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M. Yu. Gorshkova

A. V. Topchiev Institute of Petrochemical Synthesis RAS

Author for correspondence.
Email: mgor@ps.ac.ru
Russian Federation, 119991, Moscow

E. S. Gigoryan

A. V. Topchiev Institute of Petrochemical Synthesis RAS

Email: mgor@ps.ac.ru
Russian Federation, 119991, Moscow

I. F. Volkova

A. V. Topchiev Institute of Petrochemical Synthesis RAS

Email: mgor@ps.ac.ru
Russian Federation, 119991, Moscow

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Supplementary files

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2. Fig. 1. Scheme of two-stage synthesis of mHTZ.

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3. Fig. 2. Optical density at 450 nm of aqueous solutions of N-mCTZ (1), mCTZ 1 (2), mCTZ 3 (3) samples in media with different pH values.

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4. Fig. 3. IR Fourier spectra of samples of CTZ (1), N-mCTZ (2), mCTZ 1 (3).

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5. Fig. 4. Potentiometric titration curves of samples of N-mCTZ (1), mCTZ 1 (2), mCTZ 3 (3), and initial CTZ (4).

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6. Fig. 5. 13C NMR spectra of modified products N-mCTZ (a), mCTZ 1 (b) and mCTZ 3 (c) in D2O.

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7. Fig. 6. Particle sizes of polyplexes obtained with different ratios of mCTZ/DNA components (phosphate buffer, pH 7.4): 1 — N-mCTZ; 2 — mCTZ 1.

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8. Fig. 7. Particle sizes of polyplexes with the composition mCTZ/DNA = 8:1 in phosphate buffer solutions with pH 7.4 at different concentrations of NaCl salt: 1 — N-mCTZ/DNA, 2 — mCTZ 1/DNA.

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