Topical delivery of anthramycin II. Influence of binary and ternary solvent systems.

Anthramycin (ANT) is a member of the pyrolobenzodiazepine family and is a potent cytotoxic agent. Previously, we reported the topical delivery of ANT from a range of solvents that may also act as skin penetration enhancers (SPEs). The skin penetration and uptake was monitored for simple solutions of ANT in propylene glycol (PG), dipropylene glycol (DiPG), Transcutol P (TC), isopropyl myristate (IPM), propylene glycol monocaprylate (PGMC) and propylene glycol monolaurate (PGML). The amounts of PG, DiPG and TC that were taken up by, and that penetrated the skin were also measured, with a clear dependence of ANT penetration on the rate and extent of PG and TC permeation. The present work investigates ANT skin delivery from a range of binary and ternary systems to determine any potential improvement in skin uptake compared with earlier results for the neat solvents. Following miscibility and stability studies a total of eight formulations were taken forward for evaluation in human skin in vitro. Binary systems of PG and water did not result in any skin permeation of ANT. Combining PG with either PGMC or PGML did promote skin penetration of ANT but no significant improvement was evident compared with PG alone. More complex ternary systems based on PG, DiPG, PGMC, PGML and water also did not show significant improvements on ANT permeation, compared with single solvents. Total skin penetration and retention of ANT ranged from 1 to 6% across all formulations studied. Where ANT was delivered to the receptor phase there were also high amounts of PG permeation with >50% and ~35% PG present for the binary systems and ternary vehicles, respectively. These findings along with our previous paper confirm PG as a suitable solvent / SPE for ANT either alone or in combination with PGML or PGMC. The results also underline the necessity for empirical testing to determine whether or not a vehicle is acting as a SPE for a specific active in a topical formulation.

Topical delivery of anthramycin I. Influence of neat solvents.

Anthramycin (ANT) was the first pyrrolobenzodiazepine (PBD) molecule to be isolated, and is a potent cytotoxic agent. Although the PBD family has been investigated for use in systemic chemotherapy, their application in the management of actinic keratoses (AK) or skin cancer has not been investigated to date. In the present work, anthramycin (ANT) was selected as a model PBD compound, and the skin penetration of the molecule was investigated using conventional Franz diffusion cells. Finite dose permeation studies of ANT were performed using propylene glycol (PG), 1,3-butanediol (BD), dipropylene glycol (DiPG), Transcutol P® (TC), propylene glycol monocaprylate (PGMC), propylene glycol monolaurate (PGML) and isopropyl myristate (IPM). The skin penetration of BD, DiPG, PG and TC was also measured. Penetration of ANT through human skin was evident for TC, PG and PGML with the active appearing to "track" the permeation of the vehicle in the case of TC and PG. Deposition of ANT in skin could be correlated with skin retention of the vehicle in the case of IPM, PGMC and PGML. These preliminary findings confirm the ability of ANT to penetrate human skin and, given the potency of the molecule, suggest that further investigation is justified. Additionally, the findings emphasise the critical importance of understanding the fate of the excipient for the rational design of topical formulations.

Ovarian germ cell tumors.

UNLABELLED: Ovarian germ cell tumors (OGCT) are a special type of ovarian cancers due to their histology, age of presentation, prognosis and treatment. MATERIAL AND METHODS: Eighteen cases of OGCT out of 313 total ovarian cancer diagnosed in Hospital Materno-Infantil Vall d'Hebredn between 1975 and 1994 are present. RESULTS: Mean age of the patients was 36 years. The most frequent symptom at diagnosis was abdominal bloating (44.5%). Echography was the most used diagnostic method (67%). Surgery was conservative in 44% of the cases, radical in 50% of the cases and palliative in one case. The histological types were 6 dysgerminomas and 6 malignant teratomas (33.3%), 3 malignant dermoid cysts (16.7%), 2 yolk sac tumors (11%) and 1 embryonal carcinoma. According to FIGO 1987 staging classification 14 patients were in stage I disease and 4 in stage III disease. Polychemotherapy was performed on 6 patients and postsurgical radiotherapy was performed on 2 patients. Five patients recurred in an average time of 25 months. The five-year survival rate, according to the Kaplan-Meier method, was 80% in stage I and 0% in stage III. Five-year survival rate of patients only surgically treated was 65% and in patients who underwent postsurgical co-adjuvant treatment it was 100%. CONCLUSION: Conservative surgery followed by a BEP regimen may be performed nowadays with efficacy and acceptable toxicity while conserving the fertility of these patients.