Cyclodextrin functionalized agarose gel with low gelling temperature for controlled drug delivery systems

Chulgu Kim; Daham Jeong; Seonmok Kim; Yohan Kim; Seunho Jung

doi:10.1016/j.carbpol.2019.115011

Cyclodextrin functionalized agarose gel with low gelling temperature for controlled drug delivery systems

Carbohydr Polym. 2019 Oct 15:222:115011. doi: 10.1016/j.carbpol.2019.115011. Epub 2019 Jun 20.

Authors

Chulgu Kim¹, Daham Jeong², Seonmok Kim¹, Yohan Kim¹, Seunho Jung³

Affiliations

¹ Department of Bioscience and Biotechnology, Microbial Carbohydrate Resource Bank (MCRB), Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, South Korea.
² Department of Bioscience and Biotechnology, Microbial Carbohydrate Resource Bank (MCRB), Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, South Korea; Institute for Ubiquitous Information Technology and Applications (UBITA), Center for Biotechnology Research in UBITA (CBRU), Konkuk University, Seoul, 05029, South Korea.
³ Department of Bioscience and Biotechnology, Microbial Carbohydrate Resource Bank (MCRB), Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, South Korea; Institute for Ubiquitous Information Technology and Applications (UBITA), Center for Biotechnology Research in UBITA (CBRU), Konkuk University, Seoul, 05029, South Korea. Electronic address: shjung@konkuk.ac.kr.

PMID: 31320040
DOI: 10.1016/j.carbpol.2019.115011

Abstract

Conventional agaroses with high gelling temperature are limited to apply to the field of drug delivery. In this study, β-cyclodextrin (βCD) functionalized agarose (CFA) with low gelling temperature was successfully prepared from ethylenediamine-functionalized agarose using mono-succinyl βCD. The gelling temperature of CFA dramatically decreased to 26.7 °C from 65 °C and the melting temperature declined from 95 °C to 66.1 °C. Upon drug loading, CFA can be used at 30 °C because of its low gelling temperature compared to agarose. CFA gel could be used both for bovine serum albumin as a full release, and for the doxorubicin (DOX) for sustained release, via inclusion complexation of βCD. Furthermore, cytotoxicity tests revealed that CFA was noncytotoxic. DOX in the CFA gel could retain the anti-cancer activity. Newly synthesized CFA with low gelling temperature offer a new means for the development of hydrogel-based delivery systems for a variety of therapeutic drugs.

Keywords: Agarose; Drug delivery system; Hydrogel; Low gelling temperature; β-cyclodextrin; βCD functionalization.

MeSH terms

Animals
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Cattle
Doxorubicin / chemistry
Doxorubicin / pharmacology
Drug Carriers / chemical synthesis
Drug Carriers / chemistry*
Drug Carriers / toxicity
Drug Liberation
HEK293 Cells
HeLa Cells
Humans
Hydrogels / chemical synthesis
Hydrogels / chemistry*
Hydrogels / toxicity
Sepharose / chemical synthesis
Sepharose / chemistry*
Sepharose / toxicity
Serum Albumin, Bovine / chemistry
Transition Temperature
beta-Cyclodextrins / chemical synthesis
beta-Cyclodextrins / chemistry*
beta-Cyclodextrins / toxicity

Substances

Antineoplastic Agents
Drug Carriers
Hydrogels
beta-Cyclodextrins
Serum Albumin, Bovine
Doxorubicin
Sepharose