Bacterial Cellulose as Drug Delivery System for Optimizing Release of Immune Checkpoint Blocking Antibodies

Abstract

Immune checkpoint blocking therapy is a promising cancer treatment modality, though it has limitations such as systemic toxicity, which can often be traced to uncontrolled antibody spread. Controlling antibody release with delivery systems is, therefore, an attractive approach to reduce systemic antibody spread and potentially mitigate the side effects of checkpoint immunotherapy. Here, bacterial cellulose (BC) was produced and investigated as a delivery system for optimizing checkpoint-blocking antibody delivery. BC was produced in 24-well plates, and afterward, the edges were removed to obtain square-shaped BC samples with a surface of ~49 mm2. This customization was necessary to allow smooth in vivo implantation. Scanning electron microscopy revealed the dense cellulose network within BC. Human IgG antibody was included as the model antibody for loading and release studies. IgG antibody solution was injected into the center of BC samples. In vitro, all IgG was released within 24 to 48 h. Cell culture experiments demonstrated that BC neither exerted cytotoxic effects nor induced dendritic cell activation. Antibody binding assays demonstrated that BC does not hamper antibody function. Finally, antibody-loaded BC was implanted in mice, and serum measurements revealed that BC significantly reduced IgG and anti-CTLA-4 spread in mice. BC implantation did not induce side effects in mice. Altogether, BC is a promising and safe delivery system for optimizing the delivery and release of checkpoint-blocking antibodies.

Fermentation Techniques and Biotechnological Applications of Modified Bacterial Cellulose: An Up-to-Date Overview

“…The composite was synthesized by polymerizing aniline on one side of the BC membrane, forming a product that functions as a super capacitor [207]. Another study suggests the efficiency of using BC as a delivery system for optimizing the delivery and release of checkpoint-blocking antibodies, which was considered as a safe approach for cancer treatment [208].…”

Production of Bacterial Exopolysaccharides: Xanthan and Bacterial Cellulose

“…The review by Lunardi et al (2021) provides a comprehensive overview of the procedures for modifying and functionalizing nanocellulose to obtain carriers in drug delivery systems [272]. Chung et al produced BC loaded with antibodies for optimizing checkpoint-blocking antibody delivery (Figure 5C) [273]. Recently, the review by Jadav et al (2023) provided a comprehensive summary of current advances in xanthan modification to be used as an excipient in pharmaceutical formulation development, highlighting xanthan applicability to deliver various therapeutic agents such as drugs, genetic materials, proteins, and peptides [274].…”

“…Biomedical applications of xanthan and BC-based composites: BC gel film (A); xanthan-konjac glucomannan composite hydrogel for wound healing (B) (adapted from Ref [266]. (open access)); BC loaded with IgG for optimizing checkpoint-blocking antibody delivery (C) (adapted from Ref [273]. (open access)); chitosan-xanthan scaffold for chondrocytes growth (D) (adapted from Ref [321].…”