Fibrin-Rhamnogalacturonan I Composite Gel for Therapeutic Enzyme Delivery to Intestinal Tumors

Abstract

Therapy of colorectal cancer with protein drugs, including targeted therapy using monoclonal antibodies, requires the preservation of the drug’s structure and activity in the gastrointestinal tract or bloodstream. Here, we confirmed experimentally the fundamental possibility of creating composite protein–polysaccharide hydrogels based on non-degrading rhamnogalacturonan I (RG) and fibrin as a delivery vehicle for antitumor RNase binase. The method is based on enzymatic polymerization of fibrin in the presence of RG with the inclusion of liposomes, containing an encapsulated enzyme drug, into the gel network. The proposed method for fabricating a gel matrix does not require the use of cytotoxic chemical cross-linking agents and divalent cations, and contains completely biocompatible and biodegradable components. The process proceeds under physiological conditions, excluding the effect of high temperatures, organic solvents and ultrasound on protein components. Immobilization of therapeutic enzyme binase in the carrier matrix by encapsulating it in liposomes made from uncharged lipid made it possible to achieve its prolonged release with preservation of activity for a long time. The release time of binase from the composite carrier can be regulated by variation of the fibrin and RG concentration.

Microfluidic Fabrication of Calcium Alginate/Chitosan Composite Microcapsules with Ultrathin Shells for Peroxidase Immobilization

“…Enzyme immobilization is widely used in numerous fields such as sewage treatment, − biomedicine, − cell therapy, − and tissue engineering , because it can obviously improve the stability and activity of enzymes and regulate the selectivity of substrates. , Microencapsulation, as a fundamental manner for enzyme immobilization, can effectively isolate the external environment, thus protecting the internal sensitive components. , For the catalytic reaction of immobilized enzymes in microcapsules, its reaction rate significantly depends on the transport rate of substrates and products through the microcapsule shell, which can be rationally regulated by the shell thickness . Therefore, to enhance the mass transfer rate, microcapsules with ultrathin shells are always required to reduce the mass transfer resistance .…”