Mucoadhesive alginate pastes with embedded liposomes for local oral drug delivery

Yarden Shtenberg, Mor Goldfeder, Hodaya Prinz, Janna Shainsky, Yasmine Ghantous, Imad Abu El-Naaj, Avi Schroeder, Havazelet Bianco-Peled

Research output: Contribution to journalArticlepeer-review

114 Scopus citations

Abstract

Oral cancers are extremely common among adults with increasing incidences due to human papillomavirus, while treatment modalities are limited. This study aims to develop a new oral mucoadhesive delivery system based on the combination of alginate and liposomes. The polymer provides adhesion properties and induces local release of the drug-loaded carriers, while the liposomes protect the drug from degradation and improve its absorption into the cells. Three hybrid alginate/liposomes delivery systems were investigated: a hybrid paste, which presented excellent adhesive capabilities, yet fast burst release of 90% after 2 h; a hybrid hydrogel, demonstrating controllable release rates of 5%, 30% or 60% after 2 h but poor mucoadhesive properties. These findings led to the development of a hybrid cross-linked paste. Polymer retention studies demonstrated that 80% of the crosslinked paste was retained on tongue tissue compared to 50% retention of the non-cross-linked pastes, verifying its superior mucoadhesion. The hybrid cross-linked paste presented controllable release rate of 20% after 2 h. Alginate paste incorporating doxorubicin loaded liposomes presented similar release rates and were highly effective in promoting cancer cell death. Thus, our innovative formulation, including both desired characteristics of mucoadhesion and sustained liposomes release, is an important milestone in the development of a new potential treatment for oral cancer.

Original languageEnglish
Pages (from-to)62-69
Number of pages8
JournalInternational Journal of Biological Macromolecules
Volume111
DOIs
StatePublished - May 2018

Bibliographical note

Publisher Copyright:
© 2018

Funding

We would like to thank Prof. Israel Vlodavsky's lab for kindly proving the CAL-27 cell line which was used in this study. This work was supported by the Israel Ministry of Science, Technology and Space ( 3-11878 ). We gratefully thank the staff of the Technion's Lorry I. Lokey Interdisciplinary center for life Sciences & Engineering and the Russell Berrie Nanotechnology Institute & we gratefully thank the Pre-Clinical Research Authority at the Technion for their expert technical assistance. The authors wish to thank Ariela Tarnapolsky, Maayan Biton and Noi Breger for participating in the experiments. AS acknowledges the support of ERC-STG-2015-680242, the Israel Science Foundation ( 1178/3 ); the Israel Cancer Association ( 2015-0116 ); the German-Israeli Foundation for Scientific Research and Development for a GIF Young grant ( I-2328-1139.10/2012 ); the European Union FP-7 IRG Program for a Career Integration Grant ( 908049 ); a Mallat Family Foundation Grant as well as the Alon and Taub Fellowships. Appendix A

FundersFunder number
ERC-STG-2015-680242
European Union FP-7908049
Mallat Family Foundation
German-Israeli Foundation for Scientific Research and DevelopmentI-2328-1139.10/2012
Ministry of Science, Technology and Space3-11878
Israel Cancer Association2015-0116
Israel Science Foundation1178/3

    Keywords

    • Alginate
    • Drug delivery
    • Liposomes
    • Mucoadhesion
    • Oral cancer

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