The complexity of hard-to-treat diseases strongly undermines the therapeutic potential of available treatment options. Therefore, a paradigm shift from monotherapy toward combination therapy has been observed in clinical research to improve the efficiency of available treatment options. The advantages of combination therapy include the possibility of synchronous alteration of different biological pathways, reducing the required effective therapeutic dose, reducing drug resistance, and lowering the overall costs of treatment. The tunable physical properties, excellent biocompatibility, facile preparation, and ease of administration with minimal invasiveness of injectable hydrogels (IHs) have made them excellent candidates to solve the clinical and pharmacological limitations of present systems for multitherapy by direct delivery of therapeutic payloads and improving therapeutic responses through the formation of depots containing drugs, genes, cells, or a combination of them in the body after a single injection. In this review, currently available methods for the design and fabrication of IHs are systematically discussed in the first section. Next, as a step toward establishing IHs for future multimodal synergistic therapies, recent advances in cancer combination therapy, wound healing, and tissue engineering are addressed in detail in the following sections. Finally, opportunities and challenges associated with IHs for multitherapy are listed and further discussed.
Purpose The aim of this study was to introduce a smart and responsive drug carrier for Doxorubicin (DOX) and Paclitaxel (PAX) for desirable therapeutic application. Method Loading and releasing of DOX and PAX from smart and pH-sensitive functionalized single-walled carbon nanotube (SWCNTs) and graphene carriers have been simulated by molecular dynamics. The influences of chitosan polymer on proposed carriers have been studied, and both carriers were functionalized with carboxyl groups to improve the loading and releasing properties of the drugs. Results The results showed that DOX could be well adsorbed on both functionalized SWCNTs and graphene. In contrast, there was a weak electrostatic and Van der Waals interaction between both these drugs and carriers at cancerous tissues, which is highly favorable for cancer therapy. Adding trimethyl chitosan (TMC) polymer to carriers facilitated DOX release at acidic tissues. Furthermore, at blood pH, the PAX loaded on the functionalized SWCNTs carrier represented the highest dispersion of the drug while the DOX-graphene showed the highest concentration of the drug at a point. In addition, the mean-square displacement (MSD) results of PAX-graphene indicated that the PAX could be adsorbed quickly and be released slowly. Finally, functionalized graphene-TMC-PAX is a smart drug system with responsive behavior and controllable drug release, which are essential in cancer therapy. Conclusion Simultaneous application of the carboxyl group and TMC can optimize the pH sensitivity of the SWCNTs and graphene to prepare a novel and smart drug carrier for cancer therapy.
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