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Non‐Anticoagulant Heparin Prodrug Loaded Biodegradable and Injectable Thermoresponsive Hydrogels for Enhanced Anti‐Metastasis Therapy
Author(s) -
Andrgie Abegaz Tizazu,
Mekuria Shewaye Lakew,
Addisu Kefyalew Dagnew,
Hailemeskel Balkew Zewge,
Hsu WeiHsin,
Tsai HsiehChih,
Lai JuinYih
Publication year - 2019
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201800409
Subject(s) - heparin , prodrug , self healing hydrogels , metastasis , in vivo , chemistry , drug delivery , ethylene glycol , cancer , pharmacology , polymer chemistry , medicine , biochemistry , organic chemistry , biology , microbiology and biotechnology
Metastasis is a pathogenic spread of cancer cells from the primary site to surrounding tissues and distant organs, making it one of the primary challenges for effective cancer treatment and the major cause of cancer mortality. Heparin‐based biomaterials exhibit significant inhibition of cancer cell metastasis. In this study, a non‐anticoagulate heparin prodrug is developed for metastasis treatment with a localized treatment system using temperature sensitive, injectable, and biodegradable (poly‐(ε‐caprolactone‐ co ‐lactide)‐ b ‐poly(ethylene glycol)‐ b ‐poly(ε‐caprolactone‐ co ‐lactide) polymeric hydrogel. The drug molecule (heparin) is conjugated with the polymer via esterification, and its sustained release is ensured by hydrolysis and polymeric biodegradation. An aqueous solution of the polymer could be used as an injectable solution at below 25 °C and it achieves gel formation at 37 °C. The anti‐metastasis effect of the hydrogels is investigated both in vitro and in vivo. The results demonstrated that local administration of injectable heparin‐loaded hydrogels effectively promote an inhibitory effect on cancer metastasis.