Graphene Oxide/Chitosan Injectable Composite Hydrogel for Controlled Release of Doxorubicin: An Approach for Enhanced Intratumoral Delivery

Abstract

Intratumoral (IT) injection of chemotherapeutics into needle-accessible solid tumors can directly localize the anticancer drug in the tumor site, thus increasing its local bioavailability and reducing its undesirable effects compared to systemic administration. In this study, graphene oxide (GO)-based chitosan/β-glycerophosphate (CS/GP) thermosensitive injectable composite hydrogels (CH) were prepared and optimized for the localized controlled delivery of doxorubicin (DOX). A quality-by-design (QbD) approach was used to study the individual and combined effects of several formulation variables to produce optimal DOX-loaded GO/CS/GP CH with predetermined characteristics, including gelation time, injectability, porosity, and swelling capacity. The surface morphology of the optimal formulation (DOX/opt CH), chemical interaction between its ingredients and in vitro release of DOX in comparison to GO-free CS/GP CH were investigated. Cell viability and cellular uptake after treatment with DOX/opt CH were studied on MCF 7, MDB-MB-231 and FaDu cell lines. The statistical analysis of the measured responses revealed significant effects of the concentration of GO, the concentration of CS, and the CS:GP ratio on the physicochemical characteristics of the prepared GO/CS/GP CH. The optimization process showed that DOX-loaded GO/CS/GP CH prepared using 0.1% GO and 1.7% CS at a CS: GO ratio of 3:1 (v/v) had the highest desirability value. DOX/opt CH showed a porous microstructure and chemical compatibility between its ingredients. The incorporation of GO resulted in an increase in the ability of the CH matrices to control DOX release in vitro. Finally, cellular characterization showed a time-dependent increase in cytotoxicity and cellular uptake of DOX after treatment with DOX/opt CH. The proposed DOX/opt CH might be considered a promising injectable platform to control the release and increase the local bioavailability of chemotherapeutics in the treatment of solid tumors.

From antigen uptake to immune modulation: the multifaceted potential of peptide nanofibers as vaccine nanocarriers

“…29,30 Depending on the constituent materials and the methods of synthesis, nanomaterials can manifest as diverse nanostructures, such as nanospheres, nanorods, nanotubes, and nanosheets. [31][32][33][34][35][36][37][38][39][40][41] Among these, peptide nanofibers have emerged as prominent nanoarchitectures that arise from the spontaneous arrangement of peptide chains into secondary structures such as ahelical structures, peptide micelles or b-sheets, forming distinct patterns. 42,43 The design and evaluation of self-assembled peptide nanofibers have been the subject of prior reviews.…”

Hydrogel Composites for Multifunctional Biomedical Applications

“…Recent studies have placed a considerable emphasis on drug delivery systems, with hydrogel composites being developed for the controlled release of a variety of pharmaceuticals, such as efavirenz, doxorubicin, paclitaxel, and dexamethasone [23,27,[56][57][58]. This highlights the ongoing interest in enhancing the efficacy and specificity of drug delivery.…”

“…The integration of bioactive and therapeutic agents, including growth factors, enzymes, and antibiotics [1,31,[59][60][61][62][63], reflects a focus on promoting healing and regeneration while combating infection. The field is also leveraging advanced functional materials like graphene oxide, mesoporous silica nanoparticles, and metal-organic frameworks [27,64,65] to improve composite properties such as mechanical strength, bioactivity, and drug loading capacity.…”

“…Innovative combinations of materials, such as injectable nanoparticle-hydrogel systems and micelle-hydrogel composites [26,66], suggest a move toward more complex, multifunctional systems. This indicates a demand for therapies that can be administered directly to the site of injury or disease, highlighting the continued development of injectable hydrogel systems [23,26,27]. The integration of nanotechnology, through the inclusion of nanoparticles and nanozymes [64,[67][68][69], plays a critical role in enhancing the functionality of hydrogel composites, particularly for targeted drug delivery and antibacterial applications.…”

“…Targeted and controlled drug delivery techniques strive for localized, precise therapies that minimize systemic exposure and side effects. This includes developing topical delivery systems for nitric oxide [25] and injectable nanoparticle-hydrogel composites for liver cancer treatment [26], along with graphene oxide/chitosan hydrogels for targeted chemotherapy delivery [27].…”