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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.

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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.

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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.

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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.