Abstract Title

Development of Docetaxel-Loaded Lipid Nanoparticles for Prostate Cancer Treatment

Presenter Name

Asama Tanaudommongkon

Abstract

Purpose: Using docetaxel-based therapy (DTX) for treatment for men with castration-resistant prostate cancer (CRPC) showed efficacy on improving overall survival. Despite this promising outcome, toxicities and adverse events of DTX limit the dose and dosage frequency. Moreover, patients develop DTX resistance eventually. Nanoparticle (NP) drug delivery systems offer alternative therapeutic options for the treatment of prostate cancer. The goal of this study is to develop novel DTX NPs to treat CRPC.

Method: Lipid and surfactant were selected using the solubility test. DTX NPs were prepared by an emulsion method. The NPs were characterized in terms of particle size, polydispersity index, short-term stability, drug loading, drug entrapment efficiency, in vitro release study, and cytotoxicity studies in DU145 and PC3 prostate cancer cell lines.

Results: DTX NPs were prepared using a proportionally amount of Migloyl 812 as the oil phase and TPGS as the surfactant phase. All tested NPs had particle size less than 150 nm with polydispersity index of less than 0.35. DTX NPs were physically stable at 4°C over five months and in PBS at 37°C over 96 hours as measured by particle size. DTX NPs had the drug entrapment efficiency over 90% with drug loading over 5%. The cytotoxicity studies demonstrated that there was no significant difference in IC50 values for the sensitive PC3 and DU145 cells between DTX NPs and free DTX. For the resistant PC3 and DU145 cells, DTX NPs significantly reduced IC50 values compared to free DTX.

Conclusions: DTX NPs were successfully prepared and characterized. DTX NPs showed comparable cytotoxicity in sensitive prostate cancer cells, and superior cytotoxicity in resistant prostate cancer cells compared to free DTX. Therefore, DTX NPs have the potential to treat CRPC and overcome drug resistance.

This document is currently not available here.

Share

COinS
 

Development of Docetaxel-Loaded Lipid Nanoparticles for Prostate Cancer Treatment

Purpose: Using docetaxel-based therapy (DTX) for treatment for men with castration-resistant prostate cancer (CRPC) showed efficacy on improving overall survival. Despite this promising outcome, toxicities and adverse events of DTX limit the dose and dosage frequency. Moreover, patients develop DTX resistance eventually. Nanoparticle (NP) drug delivery systems offer alternative therapeutic options for the treatment of prostate cancer. The goal of this study is to develop novel DTX NPs to treat CRPC.

Method: Lipid and surfactant were selected using the solubility test. DTX NPs were prepared by an emulsion method. The NPs were characterized in terms of particle size, polydispersity index, short-term stability, drug loading, drug entrapment efficiency, in vitro release study, and cytotoxicity studies in DU145 and PC3 prostate cancer cell lines.

Results: DTX NPs were prepared using a proportionally amount of Migloyl 812 as the oil phase and TPGS as the surfactant phase. All tested NPs had particle size less than 150 nm with polydispersity index of less than 0.35. DTX NPs were physically stable at 4°C over five months and in PBS at 37°C over 96 hours as measured by particle size. DTX NPs had the drug entrapment efficiency over 90% with drug loading over 5%. The cytotoxicity studies demonstrated that there was no significant difference in IC50 values for the sensitive PC3 and DU145 cells between DTX NPs and free DTX. For the resistant PC3 and DU145 cells, DTX NPs significantly reduced IC50 values compared to free DTX.

Conclusions: DTX NPs were successfully prepared and characterized. DTX NPs showed comparable cytotoxicity in sensitive prostate cancer cells, and superior cytotoxicity in resistant prostate cancer cells compared to free DTX. Therefore, DTX NPs have the potential to treat CRPC and overcome drug resistance.