A novel injectable starch-based tissue adhesive for hemostasis.

Hemorrhage remains one of the direct causes of high mortality. The development of ideal hemostatic materials with sound ability to deal with severe wound is urgent needed. Although starch-based hemostatic powder has been widely used, hydrous physiological environments severely hamper its binding to the target tissue, thereby limiting the effectiveness in hemostasis. Herein, inspired by mussel adhesive protein, a novel injectable tissue-adhesive hydrogel (St-Dopa hydrogel) composed of starch, succinic anhydride and dopamine was developed in situ by enzymatic crosslinking. The results show that St-Dopa hydrogels were intimately integrated with biological tissue and formed robust barriers to reduce blood loss. St-Dopa hydrogels exhibited superior capacity for in vitro and in vivo hemostasis as compared with chitin hydrogels. In addition to the ease of operation, St-Dopa hydrogels exhibited rapid sol-gel transition, porous microscopic morphology, good swelling ratio and biodegradability, tissue-like elastomeric mechanical properties and excellent cyto/hemo-compatibility. These results suggest that this newly developed St-Dopa hydrogel is a promising biological adhesive and hemostatic material.

Monoglyceride-based self-assembling copolymers as carriers for poorly water-soluble drugs.

To develop self-assembling polymers forming polymeric micelles and increasing the solubility of poorly soluble drugs, amphiphilic polymers containing a hydrophilic PEG moiety and a hydrophobic moiety derived from monoglycerides and polyethers were designed. The biodegradable copolymers were obtained via a polycondensation reaction of polyethylene glycol (PEG), monooleylglyceride (MOG) and succinic anhydride (SA). Polymers with molecular weight below 10,000 g/mol containing a minimum of 40 mol% PEG and a maximum of 10 mol% MOG self-assembled spontaneously in aqueous media upon gentle mixing. They formed particles with a diameter of 10 nm although some aggregation was evident. The critical micellar concentration varied between 3x10(-4) and 4x10(-3) g/ml, depending on the polymer. The cloud point (> or = 66 degrees C) and flocculation point (> or = 0.89 M) increased with the PEG chain length. At a 1% concentration, the polymers increased the solubility of poorly water-soluble drug candidates up to 500-fold. Drug solubility increased as a function of the polymer concentration. HPMC capsules filled with these polymers disintegrated and released model drugs rapidly. Polymer with long PEG chains had a lower cytotoxicity (MTT test) on Caco-2 cells. All of these data suggest that the object polymers, in particular PEG1000/MOG/SA (45/5/50) might be potential candidates for improving the oral biopharmaceutical performance of poorly soluble drugs.

A quantitative comparison of induction and challenge concentrations inducing a 50% positive response in three skin sensitization tests; the guinea pig maximization test, adjuvant and patch test and Buehler test.

The sensitivities of three skin sensitization tests such as the Guinea pig maximization test (GPMT), Adjuvant and patch test (APT) and Buehler test (BT), were quantitatively compared with reference to induction and challenge concentrations. Four chemical which had different physico-chemical properties (octanol-water partition coefficient (logP) and reactivity with NH2-group) were used in order to clarify the effect of the physico-chemical properties of chemicals on the sensitivity of the different methods. The induction concentrations inducing a 50% positive response (IC50) demonstrated extreme variation with the three methods. For example, the BT/GPMT ratio of IC50 values for 2,4-dinitrochlorobenzene was 33, whereas that for maleic anhydride was 300,000. The results were thought to be caused by difference properties such as the logP and reactivity of chemicals. This correlation was confirmed by using 2-dodecen-1-yl succinic anhydride, which had the same reactivity but higher logP than that of maleic anhydride. On the other hand, the challenge concentrations inducing 50% positive responses (CC50) were less affected by the methods and the BT/GPMT ratios for CC50 values were all within a 10-fold range. These results suggest that the sensitivity might be strongly different with reference to induction concentration, but not challenge concentration among the three methods.