WE-AB-BRA-01: Biodistribution of Paclitaxel-Loaded Nanodroplets for Prostate Cancer Management Using Ultrasound-Mediated Drug Delivery Under MRGuidance.

PURPOSE: To study the biodistribution of paclitaxel-loaded nanodroplets in vivo in order to evaluate the efficacy of focused ultrasound (FUS)-mediated drug delivery under MR-guidance to prostate tumor.

METHODS: Poly {ethylene oxide}-co-poly {D, L-lactide} (PDLA) nanodroplets loaded with fluorescently labeled-paclitaxel (F-PTX) were synthesized using solid dispersion technique. Human prostate cancer, LNCaP cells were implanted orthotopically in prostates of male nude mice. Tumor-bearing mice (n=3) were injected with 0.1% F-PTX, 2% PDLA nanodroplets using tail vein. At chosen time points (30min; 2h; 4h; 6h; 12h; 24h) animals were anesthetized, blood was collected by eye bleed, animals were sacrificed, tumor and vital organs (liver, spleen, lung and heart) were excised, cut and weighted. Then the organ was homogenized, incubated in lysis buffer and centrifuged. The lysates were read using fluorescence spectrophotometer (Excitation- 496nm, Emission- 524nm). Fluorescence readings were compared with values from the standard calibration curve. Tumor-bearing mice (n=3) were also injected with 0.1% F-PTX solution (fluorescent drug in free form).

RESULTS: Quantitative analysis showed 20% of the injected drug-loaded nanodroplets in the tumor, 30 min after systemic injection; which increased to 30% after 2h; 35% after 4h; then decreased to 27% after 6h; 11% after 12h and 5% after 24h. When drug in free form was injected, drug accumulation in the tumor was 7% within 30mnt; 8% within 2h; 10% within 4h; 9% within 6h, 3% within 12h and 2% within 24h. Liver showed major drug accumulation for drug-loaded nanodroplets while heart and lung showed less. For drug in free form, liver and spleen showed maximum drug concentrations while heart showed concentrations similar to that in tumor.

CONCLUSION: Present work indicates that the optimum time for applying focused ultrasound is after 4h of systemically injecting drug-loaded nanodroplets. This would increase treatment efficacy and provide preclinical data for FUS-mediated drug delivery under MR-guidance.