Evaluation of the effects of chitin nanofibrils on skin function using skin models.

Chitins are highly crystalline structures that are predominantly found in crustacean shells. Alpha-chitin is composed of microfibers, which are made up of nanofibrils that are 2-5 nm in diameter and 30 nm in length and embedded in a protein matrix. Crystalline nanofibrils can also be prepared by acid treatment. We verified the effect of chitin nanofibrils (NF) and nanocrystals (NC) on skin using a three-dimensional skin culture model and Franz cells. The application of NF and NC to skin improved the epithelial granular layer and increased granular density. Furthermore, NF and NC application to the skin resulted in a lower production of TGF-ß compared to that of the control group. NF and NC might have protective effects to skin. Therefore, their potential use as components of skin-protective formulations merits consideration.

Metabolomic analyses of blood plasma after oral administration of D-glucosamine hydrochloride to dogs.

D-Glucosamine hydrochloride (GlcN∙HCl) is an endogenous amino monosaccharide synthesized from glucose that is useful in the treatment of joint diseases in both humans and animals. The aim of this study was to examine amino acid metabolism in dogs after oral administration of GlcN∙HCl. Accelerated fumarate respiration and elevated plasma levels of lactic acid and alanine were observed after administration. These results suggest that oral administration of GlcN∙HCl induces anaerobic respiration and starvation in cells, and we hypothesize that these conditions promote cartilage regeneration. Further studies are required to evaluate the expression of transforming growth factor-beta (TGF-ß).

Effects of oral glucosamine hydrochloride administration on plasma free amino acid concentrations in dogs.

We examined the effects of oral glucosamine hydrochloride (GlcN), N-acetyl-D-glucosamine (GlcNAc) and d-glucose (Glc) administration on plasma total free amino acid (PFAA) concentrations in dogs. The PFAA concentrations increased in the control group and the GlcNAc group at one hour after feeding, and each amino acid concentration increased. On the other hand, in the GlcN group and the Glc group PFAA concentrations decreased at one hour after feeding. A significant decrease in amino acid concentration was observed for glutamate, glycine and alanine. Our results suggest the existence of differences in PFAA dynamics after oral administration of GlcN and GlcNAc in dogs.

[A novel formulation of cisplatin (CDDP)].

The study aimed to assess our newly devised CDDP delivery system designed to provide targeting potential and a sustained release of the anticancer agent. Seventy percent deacetylated chitin was applied as a drug carrier. We prepared two different types of systems with two different procedures: namely, system A with direct method and system B with indirect method. The targeting property of the system was evaluated ex vivo with measuring adhesive force between each system and human colonic mucosa. The release behavior of the CDDP from the system was examined in vitro. The anticancer activities of the released CDDP were also examined in vitro using human gastric cancer cell line, MKN-45. Each system was a viscose elastic solution. The adhesive forces of the novel systems were stronger at 37 degrees C than that of 25 degrees C. Each system provided a sustained release of CDDP. The released CDDP demonstrated effective growth suppression activity against the MKN-45 cancer cells. The novel systems basically showed a favorable targeting function and a sustained release of CDDP, which effectively provided a growth inhibition potential against human cancer cell line. Our newly devised CDDP delivery systems are promising as a novel approach to cancer chemotherapy.

[Chitin/cisplatin--an adhesive anticancer drug].

The authors devised an adhesive anticancer drug delivery system using 70% deacetyalated chitin (DAC-70) and cisplatin (CDDP). We prepared two different types of the drug carriers; namely, DAC-70 viscous solution and DAC-70 lyophilized granules, which easily provided viscous solution when mixed with a liquid. We then formed a novel CDDP-loaded system by mixing each vehicle with CDDP solution. Each product showed a stronger tissue-adhesive force at 37 degrees C than that of 25 degrees C. More than 90% of total CDDP was released from the system within 24 hours. A large amount of the CDDP released from the system revealed it to be free CDDP when the DAC granule was used as the carrier, while the amount of free CDDP was less than 20% in the case of the DAC viscous solution. When the DAC-CDDP solution was given into the peritoneal cavity of rats, the CDDP remained there and only a little was transferred into the peripheral blood. We could also provide loco-regional pleurodesis by injecting the novel solution into the rat pleural cavity. These data suggest that our newly devised system has a great potential in cancer chemotherapy for the patients with malignant pleural effusion and ascites.

[A novel anticancer drug delivery system -DAC-70/CDDP].

We devised a muco-adhesive anticancer drug delivery system using 70% deacetylated chitin (DAC-70) and cisplatin (CDDP) and 5-fluorouracil (5-FU). The adhesive force between the system and human colonic mucosa was measured ex vivo, and a release profile of each drug was examined in vitro. Each system demonstrated a stronger muco-adhesive force at 37 degrees C than that of 25 degrees C. The CDDP-loaded system showed a sustained release of the drug while the 5-FU-loaded system exhibited an initial bursting of the agent. We presume that the release profile of CDDP and 5-FU is closely related to both degradability of the chitin and interactions between the chitin and each drug. The DAC-70/CDDP system would be clinically promising in loco-regional cancer chemotherapy.

[A novel approach to loco-regional cancer chemotherapy with a chitosan-CDDP solution].

The authors applied 70% deacetylated chitin (DAC 70, chitosan) as a vehicle of cis-platinum (CDDP) to achieve loco-regional cancer chemotherapy, in an attempt to hold the drug in the target region with a locally sustained release. The DAC-70 powder was dissolved in a 0.1 M HCI solution into where CDDP solution and glycerol phosphate solution were added. The resulting product, DAC-70/CDDP became a muco-adhesive solution. The adhesiveness between the solution and human colonic mucosa was measured ex vivo by our own method, and a release profile of the CDDP was examined in vitro using an atomic absorption method. The adhesive force was stronger at 37 degrees C than that of at 25 degrees C. Ten percent of the CDDP was gradually delivered for 6 hours, while the release was maintained at the same levels for the following 72 hours. The release rate increased by 10-20% when lysozyme was added in the incubation systems. However, the release profile of the drug showed no remarkable changes. The DAC-70/CDDP solution provided a favorable adhesiveness with human colonic mucosa, while in situ degradability of the solution should be improved further more.