Protective effect of Carbopol on enzymatic degradation of a peptide-like substrate. I: Effect of various concentrations and grades of Carbopol and other reaction variables on trypsin activity.

The purpose of this study was to determine and compare the effect of various concentrations and grades of Carbopol on trypsin-induced degradation of a prototype substrate, N(alpha)-benzoyl-L-arginine ethyl ester hydrochloride (BAEE). Effect of other reaction variables, such as viscosity and ionic strength of the medium on the trypsin activity, was also analyzed simultaneously. Four concentrations and three commercially available grades of Carbopol were used. The effect of Carbopol was expressed in terms of change in the velocity of degradation reaction. A modified trypsin assay was developed and used for analysis. Up to a concentration of 0.35% w/v, Carbopol 934P showed a concentration-dependent increase in its ability to reduce the rate of enzymatic hydrolysis of BAEE. Similar inhibitory effect was observed with all three grades of Carbopol. The activity of trypsin was unaffected by other reaction variables, suggesting that interaction between the protein and the polymer could be the mechanism responsible for reduced trypsin activity. This study suggests that Carbopol can be a useful excipient for oral delivery of bioactive proteins and peptides, due to its ability to reduce the enzyme-induced degradation of these agents.

Treatment of uterine papillary serous carcinoma with platinum-based chemotherapy and paclitaxel.

Uterine papillary serous carcinoma (UPSC) is more aggressive than endometrioid endometrial cancer, as it often presents with advanced disease and follows a pattern of spread that resembles the serous carcinoma of the ovary. There exists little data on evaluating the combination of carboplatin and paclitaxel in UPSC. Institutional Review Board permission was obtained for a retrospective review. Tumor registry search was used to identify all patients with UPSC from 1990 to 2003. Charts were retrospectively evaluated from patients who had received at least three cycles of carboplatin and paclitaxel as first-line chemotherapy. Only patients with histologically confirmed UPSC who were treated first line with carboplatin/paclitaxel chemotherapy were included. Nineteen patients with UPSC were identified, who were treated with carboplatin and paclitaxel in the first-line adjuvant setting after initial surgical cytoreduction. All patients received at least three cycles, with 12 of the 19 patients receiving six cycles. Five patients were treated with consolidation radiotherapy following first-line chemotherapy. Mean age was 69 years (range 55-88). The majority of patients had stage III disease (n= 11). Mean follow-up for the group was 29.5 months (7-76 months). A median progression-free interval of 12 months was seen across the entire cohort. Fourteen patients achieved a complete response following chemotherapy. The results of Gynecologic Oncology Group protocol 122 suggest that patients with advanced endometrial cancer have an improved progression-free survival when treated primarily with chemotherapy rather than radiation therapy. The results of our study show a high response rate to paclitaxel/carboplatin outpatient chemotherapy in a group of patients historically believed to have chemoresistant disease. Further prospective study of this regimen is planned.