Biodegradable thermoresponsive oligochitosan nanoparticles: Mechanisms of phase transition and drug binding-release.

Tatiana V Burova, Valerij Y Grinberg, Natalia V Grinberg, Alexander S Dubovik, Vladimir E Tikhonov, Victor N Orlov, Irina G Plashchina, Carmen Alvarez-Lorenzo, Alexei R Khokhlov

International journal of biological macromolecules 2020 Dec 01

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Oligochitosan, a low molecular weight derivative of the cationic biopolymer, chitosan, currently shows a great potential of application as a biodegradable non-toxic stimuli-sensitive drug carrier. This paper aimed to elucidate the thermoresponsive potential of oligochitosan and the temperature-controlled drug binding and release to shed light on oligochitosan potential in stimuli-responsive drug delivery. Mechanisms of thermoresponsive behavior of oligochitosan induced by β-glycerophosphate (GP) were investigated using ITC, DSC, and DLS. Upon heating, the aqueous oligochitosan solution underwent a cooperative transition of the microphase separation type resulting in the formation of stable nano-sized particles. Energetics of the GP-oligochitosan interaction (evaluated by ITC) revealed a positive enthalpy of the GP binding to oligochitosan, which pointed to a notable contribution of dehydration and the related rearrangement of the polysaccharide hydration shell. Energetics of the thermal phase transition of oligochitosan was investigated by DSC upon variation of the solvent dielectric constant and GP concentration. The dependences of the transition parameters on these variables were determined and used for the analysis of the oligochitosan thermoresponsivity mechanism. The binding of ibuprofen to the thermotropic oligochitosan nanogel particles and its release from them were evaluated under near-physiological conditions. Relevantly, the oligochitosan nanoparticles surpassed some reference macromolecular adsorbers by the affinity for the drug and by the delayed release kinetics. Copyright © 2020 Elsevier B.V. All rights reserved.

Citation

Tatiana V Burova, Valerij Y Grinberg, Natalia V Grinberg, Alexander S Dubovik, Vladimir E Tikhonov, Victor N Orlov, Irina G Plashchina, Carmen Alvarez-Lorenzo, Alexei R Khokhlov. Biodegradable thermoresponsive oligochitosan nanoparticles: Mechanisms of phase transition and drug binding-release. International journal of biological macromolecules. 2020 Dec 01;164:1451-1460