Encrypted login | home

Program Information

Development of Docetaxel Encapsulated, Ultrasound-Responsive Nanodroplets for Treatment of Prostate Cancer

R Gupta

R Gupta*, D Cvetkovic, X Chen, C Ma, L Chen, Fox Chase Cancer Center, Philadelphia, PA

SU-E-U-1 Sunday 3:00PM - 6:00PM Room: Exhibit Hall

Purpose: To formulate ultrasound-responsive nanodroplets loaded with Docetaxel (DTX) drug molecules for efficient delivery into the prostate tumor while minimizing drug related toxicities.

Methods:Five mg of DTX and 20 mg of biodegradable amphiphilic block copolymer {poly (ethylene oxide)-co-poly (D, L-lactide)} (PEG-PDLA) with a molecular weight of either block of 2000 Da, were co-dissolved in 1ml of tetrahydrofuran (THF). The THF was then evaporated under gentle nitrogen stream at 60°C or pumped out at room temperature. The residual gel matrix obtained was dissolved in 1ml of phosphate buffered saline (pH 7.4) to form polymeric micelles. Subsequently, 20 microlitre of Perfluorocarbon (PFCE) was introduced into this micellar solution and the mixture was emulsified on ice using the ultrasonic processor (Fig.1) (VCX500, Sonics and Materials Inc., CT, USA) to obtain docetaxel-loaded droplets of the composition- 2% PEG-PDLA- 0.1% DTX- 2% PFCE (Fig.2). Size distribution of nanodroplets was measured by dynamic light scattering using DynaPro Plate Reader (Fig.3) (Wyatt technology, Santa Barbara, CA).

Results:Our results showed that the mean diameter of the drug-loaded nanodroplets was 220 ± 30nm. Based on published data, the size of the drug-loaded nanodroplet allows effective accumulation in most tumor types via Enhanced Permeability and Retention (EPR) effect. The core of the nanodroplets containing PFCE is expected to be converted into micro bubbles by pulsed focused ultrasound resulting in localized drug release.

Conclusion:We have successfully developed techniques for formulation of docetaxel-encapsulated nanodroplets which responds to ultrasound. Studies were carried out to characterize the effect of docetaxel-loaded nanodroplets on the treatment of prostate cancer (LNCaP cell line) in vitro. The treatment effects on tumor growth control were also evaluated using an orthotopic animal prostate tumor model. The results of these studies are reported elsewhere in this meeting.

Contact Email: