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Comparative Study
. 2007 Oct 15;121(8):1830-8.
doi: 10.1002/ijc.22886.

Paclitaxel and Ceramide Co-Administration in Biodegradable Polymeric Nanoparticulate Delivery System to Overcome Drug Resistance in Ovarian Cancer

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Comparative Study

Paclitaxel and Ceramide Co-Administration in Biodegradable Polymeric Nanoparticulate Delivery System to Overcome Drug Resistance in Ovarian Cancer

Harikrishna Devalapally et al. Int J Cancer. .
Free article

Abstract

The objective of this study was to overcome drug resistance upon systemic administration of combination paclitaxel (PTX) and the apoptotic signaling molecule C(6)-ceramide (CER) in biodegradable poly(ethylene oxide)-modified poly(epsilon-caprolactone (PEO-PCL) nanoparticles. Subcutaneous sensitive (wild-type) and multidrug resistant (MDR-1 positive) SKOV-3 human ovarian adenocarcinoma xenografts were established in female Nu/Nu mice. PTX and CER were administered intravenously either as a single agent or in combination in aqueous solution and in PEO-PCL nanoparticles to the tumor-bearing mice. There was significant (p< 0.05) tumor growth suppression in both wild-type SKOV-3 and multidrug resistant SKOV-3(TR) models upon single dose co-administration of PTX (20 mg/kg) and CER (100 mg/kg) in nanoparticle formulations as compared to the individual agents and administration in aqueous solutions. For instance, in SKOV-3 wild-type model, more than 4.3-fold increase (p < 0.05) in tumor growth delay and 3.6-fold (p < 0.05) increase in tumor volume doubling time (DT) were observed with the combination treatment in nanoparticles as compared to untreated animals. Similarly, 3-fold increase (p < 0.05) in tumor growth delay and tumor volume DT was observed in SKOV-3(TR) model. Body weight changes and blood cells counts were used as measures of safety and, except for an increase in platelet counts (p < 0.05) in PTX + CER treated animals, there was no difference between various treatment strategies. The results of this study show that combination of PTX and CER in biodegradable polymeric nanoparticles can serve as a very effective therapeutic strategy to overcome drug resistance in ovarian cancer.

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