Gum arabic with multialdehyde groups
(GAMA) was synthesized and
utilized as a naturally derived macromolecular and nontoxic cross-linker
to develop biocompatible and smart succinic anhydride-modified chitosan
(SCS)-based injectable hydrogels for the first time. Aqueous solutions
of GAMA and SCS were mixed at 37 °C to obtain hydrogels through
pH-responsive, dynamic, and biodegradable Schiff base linkages. The
effect of concentration of GAMA on hydrogel stiffness, swelling, morphology,
and drug release behavior was investigated. These hydrogels exhibited
outstanding self-healing and mechanical properties. Nanocurcumin as
a chemotherapeutic agent was synthesized and loaded into these hydrogels
for release studies carried out at pH 7.4 and 5.5. MTT assay revealed
that these hydrogels are nontoxic to human embryonic kidney cell line
(HEK-293). Loaded hydrogels demonstrated significant cytotoxicity
against breast cancer cell line (MCF-7). Thus, the present strategy
may find promising application for controlled delivery of anticancer
drugs for treating locally accessible cancers.
The
chemically oxidized gum arabic was prepared and used as a naturally
derived nontoxic and pH-responsive cross-linker to develop smart polyvinyl
alcohol (PVA)-based hydrogels for the first time. The formulated hydrogels
exhibited high mechanical properties, good porosity, and pH sensitivity,
which facilitated their application as promising biomaterials for
sustained delivery of folic acid. Further, the synthesized cross-linked
PVA hydrogels displayed no cytotoxicity toward the human embryonic
kidney cell line and exhibited higher blood compatibility. The hydrolytic
degradation study confirmed their biodegradable nature. While the
sustained delivery along with photoprotective properties of these
hydrogels confirmed their multifunctional characteristics, these results
suggest that these hydrogels may act as an efficient photoprotective
material and find their application in the field of drug delivery.
In the present study, luteolin (LTN)-encapsulated chitosan (CS) coated nanostructured lipid carriers (NLCs) were formulated using the melt emulsification ultrasonication technique. NLCs were optimized by using the 33-QbD approach for improved in vitro efficacy against breast cancer cell lines. The optimized LTN-CS-NLCs were successfully characterized by different in vitro and ex vivo experiments as well as evaluated for cytotoxicity in MDA-MB-231 and MCF-7 cell lines. The prepared LTN-CS-NLCs showed particle size (PS), polydispersity index (PDI), and entrapment efficiency (%EE) in the range between 101.25 nm and 158.04 nm, 0.11 and 0.20, and 65.55% and 95.37%, respectively. Coating of NLCs with CS significantly increased the particle size, encapsulation efficiency, and zeta potential changes positively. Moreover, slow-release rate of LTN was achieved during 24 h of study for LTN-CS-NLCs. In addition, optimized LTN-CS-NLCs showed significantly higher mucoadhesion, gastrointestinal stability, and intestinal permeation compared to non-coated LTN-NLCs and LTN suspension. Furthermore, LTN-CS-NLCs showed statistically enhanced antioxidant potential as well as dose and time-dependent cytotoxicity against MDA-MB-231 and MCF-7 cells compared to uncoated LTN-NLCs and pure LTN. On the basis of the above findings, it may be stated that chitosan-coated LTN-NLCs represents a great potential for breast cancer management.
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.
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