Local
delivery of anticancer agents via injectable hydrogels could
be a promising method for achieving spatiotemporal control on drug
release as well as minimizing the disadvantages related to the systemic
mode of drug delivery. Keeping this in mind, we report the development
of N,O-carboxymethyl chitosan (N,O-CMCS)–guar gum-based injectable
hydrogels for the sustained delivery of anticancer drugs. The hydrogels
were synthesized by chemical crosslinking of multialdehyde guar gum
(MAGG) and N,O-CMCS through dynamic
Schiff base linkages, without requiring any external crosslinker.
Fabrication of injectable hydrogels, involving N,O-CMCS and MAGG via Schiff base crosslinking, is being reported
for the first time. The hydrogels exhibited pH-responsive swelling
behavior and good mechanical properties with a storage modulus of
about 1625 Pa. Due to the reversible nature of Schiff base linkages,
hydrogels displayed excellent self-healing and thixotropic properties.
Doxorubicin (Dox), an anticancer agent, was loaded onto these hydrogels
and its release studies were conducted at pH 7.4 (physiological) and
pH 5.5 (tumoral). A sustained release of about 67.06% Dox was observed
from the hydrogel after 5 days at pH 5.5 and about 32.13% at pH 7.4.
The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
assay on the human embryonic kidney cell line (HEK-293) and the hemolytic
assay demonstrated the biocompatible nature of the hydrogels. The
Dox-loaded hydrogel exhibited a significant killing effect against
breast cancer cells (MCF-7) with a cytotoxicity of about 72.13%. All
the data presented support the efficiency of the synthesized N,O-CMCS/MAGG hydrogel as a biomaterial
that may find promising applications in anticancer drug delivery.
We report the synthesis of a novel photocleavable crosslinker and its joining with amine-based polysachharides, viz. chitosan, resulting in the formation of a dual stimuli-responsive hydrogel having UV- and pH-responsive sites.
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