The purpose of this study was to clarify the adsorption of cisplatin on regenerative-medicine (RM) gelatin sponge, and to verify the relationship between the cisplatin release pattern of cisplatin-adsorbed RM gelatin sponge and the dissolving time of RM gelatin sponge. We tested various RM gelatin sponges, one with a molecular weight of 50000 Daltons (RM-50 gelatin sponge) that is 100% saline soluble at 24 h, RM-50-120 (heated at 120°C) that is 54.3% saline soluble at 24 h, and RM-50-140 (heated at 140°C) that is 15.8% saline soluble at 24 h. We investigated the production of cisplatin-adsorbed RM gelatin sponge and measured free cisplatin released from cisplatin-adsorbed RM gelatin sponge. There was no significant difference in the weight of adsorbed cisplatin among the RM-50, RM-50-120, and RM-50-140. The results mean that cisplatin adsorbs onto RM gelatin sponge irrespective of heating temperature. The average adsorbed weight of cisplatin per gram of RM gelatin sponge was 29.3 mg, which was approximately five times more than that per g previously reported for Gelpart (non-soluble gelatin sponge, clinically available). Cisplatin release in the RM-50 gelatin was the most rapid at only 1 h after incubation; it was released gradually and increasingly in the RM-50-120 gelatin, and released slowly in the RM-50-140 gelatin for 24 h incubation. Cisplatin-adsorbed RM gelatin sponge released cisplatin proportional to the dissolving time of RM gelatin sponge, indicating that the cisplatin release time can be controlled by heating for sterilization of RM gelatin sponge.
Key words regenerative-medicine (RM) gelatin; endotoxin; cisplatin; drug delivery system (DDS); transcatheter arterial chemoembolization (TACE)Gelatin has been extensively used by pharmaceutical manufactures as a pharmaceutical excipient (stabilizer, additive, etc.) Furthermore, it is used as a material for biomaterials. For example, it is used in the biomaterial sheet to facilitate regeneration of dermis to cover a skin deficit.1,2) The endotoxin in gelatin is lipopolysaccharide (LPS), which is the same component as the outer envelope of Gram-negative bacteria, and is commonly isolated from Gram-negative bacteria. The collapse of the cell wall due to autolysis and denaturation would cause much more LPS to be released, damaging various types of cells. [3][4][5] When LPS invades the body, it causes fever and can cause septic shock.6-8) Sterilization to 121°C is insufficient to eradicate endotoxic activity, this requires heating at 250°C for more than 60 min.9) It is preferable to use gelatin without bacteria or endotoxins when this biomaterial is to be introduced into the body. The gelatin that matches the standard for purified gelatin in Japanese Pharmacopoeia in this regard was developed in 2007, and is termed regenerative-medicine (RM) gelatin. RM gelatin was removed endotoxin using an ultra filtration membrane without heat sterilization at 250°C.
10)We created cisplatin-adsorbing RM gelatin sponge. The solubility of dried RM gelatin sponge can be contr...