Towards in vivo photomediated delivery of anticancer peptides: Insights from pharmacokinetic and -dynamic data.

An in vivo study of a photoswitchable cytotoxic peptide LMB040 has been undertaken on a chemically induced hepatocellular carcinoma model in immunocompetent rats. We analysed the pharmacokinetic profile of the less toxic photoform ("ring-closed" dithienylethene) of the compound in tumors, plasma, and healthy liver. Accordingly, the peptide can reach a tumor concentration sufficiently high to exert a cytotoxic effect upon photoconversion into the more active ("ring-open") photoform. Tissue morphology, histology, redox state of the liver, and hepatic biochemical parameters in blood serum were analysed upon treatment with (i) the less active photoform, (ii) the in vivo light-activated alternative photoform, and (iii) compared with a reference chemotherapeutic 5-fluorouracil. We found that application of the less toxic form followed by a delayed in vivo photoconversion into the more toxic ring-open form of LMB040 led to a higher overall survival of the animals, and signs of enhanced immune response were observed compared to the untreated animals.

Desmopressin stimulates bile secretion in anesthetized rats.

One of the synthetic analogues of antidiuretic hormone-desmopressin is used in patients with central diabetes insipidus and in those with coagulation disorders. However, its effects on bile secretion are not fully defined. We investigated the effect of desmopressin on bile formation and determined the role of V1a vasopressin receptors in the action of desmopressin on choleresis. Rats were injected intraportally with a bolus of desmopressin; the changes of bile flow, the content of free and conjugated cholates were compared with control animal group. Selective antagonist of V1a receptors was injected 10 minutes before desmopressin treatment and the findings were compared with the results after desmopressin injection alone. Desmopressin increased bile flow, secretion of total cholates like amino acids conjugated, while diminished free bile acids content. Secreted bile volume and conjugated bile acids content were reduced in V1a receptors antagonist+desmopressin-treated rats. In contrast, free bile acids content was more than the results in desmopressin-treated rats. Desmopressin at concentrations nearly equal to physiological concentrations of natural hormone in blood shows its choleretic effect. Antagonist of V1a vasopressin receptors modulates desmopressin action. This certifies the role of these receptors in the action of desmopressin on different processes of bile formation.