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Double cross-linked pectin beads stable in physiological environment as potential support for biomedical applications

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Abstract

Calcium-pectin beads are largely used for biomedical applications, however, the main drawback is their rapid disintegration in the presence of chelating and non-chelating ions from body fluids. Therefore, the principal goal of this work is to produce stable pectin beads by successive ionic and covalent cross-linking and to test their stability in simulated physiological conditions. For this purpose, native pectin was first de-esterified (DEP) to result a maximum amount of carboxylic groups, then a fraction of the DEP was oxidized with NaIO4 (OXP) to introduce aldehyde groups susceptible to covalent cross-linking. Finally, the de-methylated and de-methylated/oxidized pectin were mixed and transformed into beads by double cross-linking: ionic with calcium ions and covalent with adipic acid dihydrazide (ADH). The gelling properties, sphericity and shape as well as the morphology and the stability of the beads in different media were investigated. Finally, beads were tested for their capacity to encapsulate and release drug molecule. Therefore, microcapsules were loaded with FITC-dextran, a standard high molecular weight model drug molecule, with high encapsulation efficiency. A remarkable delay in FITC-dextran release was observed for DEP/OXP beads compared to DEP particles. The transport mechanism of solvent and FITC-dextran in/from the DEP/OXP beads was determined as a Fickian diffusion-driven. The viability tests proved that both simple and double cross-linked microcapsules are cytocompatible for the HEK-293 cells at pectin concentrations up to 5.5 mg/mL.

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Funding

This work was supported by a grant of the Romanian Ministry of Research and Innovation, CCDI-UEFISCDI, project number PN-III-P1-1.2.-PCCDI-2017–0697/contract nr. 13PCCDI/2018 within PNCDI III (INTERA) and by the European Social Fund for Regional Development, Competitiveness Operational Programme Axis 1 – Project “Petru Poni” Institute of Macromolecular Chemistry-Interdisciplinary Pol for Smart Specialization through Research and Innovation and Technology Transfer in Bio(nano)polymeric Materials and (Eco)Technology”, InoMatPol (ID P_36_570, Contract 142/10.10.2016, cod MySMIS: 107464).

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Authors and Affiliations

  1. Natural Polymers, Bioactive and Biocompatible Materials Laboratory, Petru Poni Institute of Macromolecular Chemistry, Grigore Ghica Voda Alley 41A, Iasi, 700487, Romania

    Irina Popescu, Mihail Lupei, Marieta Constantin & Gheorghe Fundueanu

  2. Medical and Pharmaceutical Bionanotechnologies Laboratory, Institute of Cellular Biology and Pathology Nicolae Simionescu of the Romanian Academy, 050568, Bucharest, Romania

    Geanina Voicu & Manuela Calin

  3. Fiterman Pharma SRL, Păcurari St. No. 127, Iasi, 700544, Romania

    Anca Irina Prisacaru

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  1. Irina Popescu
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  2. Mihail Lupei
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  3. Marieta Constantin
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  4. Geanina Voicu
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  5. Manuela Calin
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  6. Anca Irina Prisacaru
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  7. Gheorghe Fundueanu
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Contributions

Conceptualization: Marieta Constantin and Gheorghe Fundueanu; Methodology: Irina Popescu and Marieta Constantin; Investigation: Mihail Lupei, Irina Popescu, Geanina Voicu, and Anca Irina Prisacaru; Writing – original draft preparation: Irina Popescu and Marieta Constantin; Writing—review and editing: Gheorghe Fundueanu and Manuela Calin; Supervision: Gheorghe Fundueanu.

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Popescu, I., Lupei, M., Constantin, M. et al. Double cross-linked pectin beads stable in physiological environment as potential support for biomedical applications. J Polym Res 28, 424 (2021). https://doi.org/10.1007/s10965-021-02779-5

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