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The growing complexity of cancer treatment requires new drug delivery systems that improve the effectiveness of therapy and reduce adverse effects. This study explores the potential of using bacterial ghosts (BGs) in combination with hydrogels to develop a targeted drug delivery system for cancer treatment. BGs, based on non-pathogenic bacteria, offer several distinct advantages, including biocompatibility, maintenance of immunogenicity, and effective encapsulation of therapeutic agents. The BG-hydrogel system enhances stability and controlled release of encapsulated drugs, which enhances the therapeutic window of drugs. Herein, the BGs were loaded with the anticancer drug doxorubicin (DOX) and subsequently encapsulated in four different hydrogels, namely agarose, agar, aloe vera, and sodium alginate, to produce a Bacterial Ghost-Hydrogel System (BG-HS). The BGs, DOX-loaded BGs, hydrogels, and BG-HS morphologies were characterized by Scanning Electron Microscopy (SEM), revealing distinct structural features conducive to drug delivery applications. Detailed chemical analysis was conducted using Fourier Transform Infrared Spectroscopy (FTIR), confirming the presence of all individual components in the BG-HS. UV-vis spectroscopy demonstrated a pH-responsive drug-release profile attributed to hydrogel ionization in acidic and basic solutions. Compression testing was used to evaluate the mechanical integrity of hydrogels for in vivo applications. Also, a macroscopic diffusion experiment with a model solute (Rhodamine-6B) was performed to identify the hydrogel with the highest transport performance. The study's results indicate that BGs with natural hydrogels, particularly agarose, are a promising approach for future cancer therapy and warrant further preclinical and clinical research.
