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Encapsulation of Antitumor Drug Doxorubicin and Its Analogue by Chitosan Nanoparticles

Sanyakamdhorn, Sriwanna, Agudelo, Daniel, Tajmir-Riahi, Heidar-Ali
Biomacromolecules 2013 v.14 no.2 pp. 557-563
Fourier transform infrared spectroscopy, aqueous solutions, biodegradability, chemical elements, chitosan, doxorubicin, encapsulation, energy, fluorescence, hydrogen bonding, hydrophilicity, hydrophobicity, molecular models, nanoparticles, polymers
Biodegradable chitosan of different sizes were used to encapsulate antitumor drug doxorubicin (Dox) and its N-(trifluoroacetyl) doxorubicin (FDox) analogue. The complexation of Dox and FDox with chitosan 15, 100, and 200 KD was investigated in aqueous solution, using FTIR, fluorescence spectroscopic methods, and molecular modeling. The structural analysis showed that Dox and FDox bind chitosan via both hydrophilic and hydrophobic contacts with overall binding constants of KDₒₓ₋cₕ₋₁₅ = 8.4 (±0.6) × 10³ M–¹, KDₒₓ₋cₕ₋₁₀₀ = 2.2 (±0.3) × 10⁵ M–¹, KDₒₓ₋cₕ₋₂₀₀ = 3.7 (±0.5) × 10⁴ M–¹, KFDₒₓ₋cₕ₋₁₅ = 5.5 (±0.5) × 10³ M–¹, KFDₒₓ₋cₕ₋₁₀₀ = 6.8 (±0.6) × 10⁴ M–¹, and KFDₒₓ₋cₕ₋₂₀₀ = 2.9 (±0.5) × 10⁴ M–¹, with the number of drug molecules bound per chitosan (n) ranging from 1.2 to 0.5. The order of binding is ch-100 > 200 > 15 KD, with stronger complexes formed with Dox than FDox. The molecular modeling showed the participation of polymer charged NH₂ residues with drug OH and NH₂ groups in the drug–polymer adducts. The presence of the hydrogen-bonding system in FDox-chitosan adducts stabilizes the drug–polymer complexation, with the free binding energy of −3.89 kcal/mol for Dox and −3.76 kcal/mol for FDox complexes. The results show chitosan 100 KD is a more suitable carrier for Dox and FDox delivery.