Hyperbranched poly(amine-ester) based hydrogels for controlled multi-drug release in combination chemotherapy.
Combination chemotherapy has been a primary management for cancer. Thus a drug delivery system which can administer several drugs simultaneously and control the drug release at the cancer site is desired. Here we synthesized hyperbranched poly(amine-ester) (HPAE) macromers with different degrees of terminal CC modification to make injectable hydrogels as a multi-drug delivery system. The aqueous solutions of the macromers were fast transformed into hydrogel at body temperature with a low concentration (0.05 wt%) of ammonium persulfate (APS) but no activator for accelerating the polymerization, since the HPAE macromer with tertiary amines and APS themselves formed a redox system as initiator. Three different types of drugs, doxorubicin hydrochloride (Dox), 5-fluorouracil (5FU) and leucovorin calcium (LC), were used as model drugs in this experiment. This system allows locally releasing single and/or combinations of anticancer drugs simultaneously by a controllable way. Behaviors of drug release can be controlled by the drug-loading methods or/and the CC modification degree of macromers loaded with the drug molecules. The drug release period could be prolonged when the drug was loaded into the macromers with high content of CC. The HPAE macromers exhibited good biocompatibility which was evaluated in L929 and MCF7 cell lines using MTT cell proliferation assay. The swelling behavior and degradation of HPAE hydrogels in vitro were also examined. These results suggest that the HPAE hydrogels hold great potential for use as injectable systems for locally delivering single and/or multiple drugs in chemotherapy of cancer.
Zhang
Hongbin
H
School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083, PR China.
Zhao
Chen
C
Cao
Hui
H
Wang
Guojie
G
Song
Li
L
Niu
Guoguang
G
Yang
Huai
H
Ma
Jie
J
Zhu
Siquan
S
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002460:Cell Line; D003692:Delayed-Action Preparations; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry*; D004317:Doxorubicin / Q000494:pharmacology; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry*; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D002955:Leucovorin / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008422:Materials Testing; D051379:Mice; D008970:Molecular Weight; D013997:Time Factors
D003692:Delayed-Action Preparations; D050091:Dendrimers; D004952:Esters; D020100:Hydrogels; D004317:Doxorubicin; D002955:Leucovorin; D005472:Fluorouracil