Novel docetaxel-loaded nanoparticles based on poly(lactide-co-caprolactone) and poly(lactide-co-glycolide-co-caprolactone) for prostate cancer treatment: formulation, characterization, and cytotoxicity studies

<p>Abstract</p> <p>Docetaxel (Dtx) chemotherapy is the optional treatment in patients with hormone-refractory metastatic prostate cancer, and Dtx-loaded polymeric nanoparticles (NPs) have the potential to induce durable clinical responses. However, alternative formulations are need...

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Main Authors: Sechi Mario, Posadino Anna, Cossu Annalisa, Pintus Gianfranco, Mariani Alberto, Alzari Valeria, Marceddu Salvatore, Sanna Vanna, Roggio Anna, Uzzau Sergio
Format: Article
Language:English
Published: SpringerOpen 2011-01-01
Series:Nanoscale Research Letters
Online Access:http://www.nanoscalereslett.com/content/6/1/260
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author Sechi Mario
Posadino Anna
Cossu Annalisa
Pintus Gianfranco
Mariani Alberto
Alzari Valeria
Marceddu Salvatore
Sanna Vanna
Roggio Anna
Uzzau Sergio
author_facet Sechi Mario
Posadino Anna
Cossu Annalisa
Pintus Gianfranco
Mariani Alberto
Alzari Valeria
Marceddu Salvatore
Sanna Vanna
Roggio Anna
Uzzau Sergio
author_sort Sechi Mario
collection DOAJ
description <p>Abstract</p> <p>Docetaxel (Dtx) chemotherapy is the optional treatment in patients with hormone-refractory metastatic prostate cancer, and Dtx-loaded polymeric nanoparticles (NPs) have the potential to induce durable clinical responses. However, alternative formulations are needed to overcome the serious side effects, also due to the adjuvant used, and to improve the clinical efficacy of the drug.</p> <p>In the present study, two novel biodegradable <it>block</it>-copolymers, poly(lactide-co-caprolactone) (PLA-PCL) and poly(lactide-co-caprolactone-co-glycolide) (PLGA-PCL), were explored for the formulation of Dtx-loaded NPs and compared with PLA- and PLGA-NPs. The nanosystems were prepared by an original nanoprecipitation method, using Pluronic F-127 as surfactant agent, and were characterized in terms of morphology, size distribution, encapsulation efficiency, crystalline structure, and <it>in vitro </it>release. To evaluate the potential anticancer efficacy of a nanoparticulate system, <it>in vitro </it>cytotoxicity studies on human prostate cancer cell line (PC3) were carried out. NPs were found to be of spherical shape with an average diameter in the range of 100 to 200 nm and a unimodal particle size distribution. Dtx was incorporated into the PLGA-PCL NPs with higher (<it>p </it>&lt; 0.05) encapsulation efficiency than that of other polymers. Differential scanning calorimetry suggested that Dtx was molecularly dispersed in the polymeric matrices. <it>In vitro </it>drug release study showed that release profiles of Dtx varied on the bases of characteristics of polymers used for formulation. PLA-PCL and PLGA-PCL drug loaded NPs shared an overlapping release profiles, and are able to release about 90% of drug within 6 h, when compared with PLA- and PLGA-NPs. Moreover, cytotoxicity studies demonstrated advantages of the Dtx-loaded PLGA-PCL NPs over pure Dtx in both time- and concentration-dependent manner. In particular, an increase of 20% of PC3 growth inhibition was determined by PLGA-PCL NPs with respect to free drug after 72 h incubation and at all tested Dtx concentration. In summary, PLGA-PCL copolymer may be considered as an attractive and promising polymeric material for the formulation of Dtx NPs as delivery system for prostate cancer treatment, and can also be pursued as a validated system in a more large context.</p>
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spelling doaj.art-d5c533adf2d34dafae3c10ef679b033f2023-09-02T12:14:22ZengSpringerOpenNanoscale Research Letters1931-75731556-276X2011-01-0161260Novel docetaxel-loaded nanoparticles based on poly(lactide-co-caprolactone) and poly(lactide-co-glycolide-co-caprolactone) for prostate cancer treatment: formulation, characterization, and cytotoxicity studiesSechi MarioPosadino AnnaCossu AnnalisaPintus GianfrancoMariani AlbertoAlzari ValeriaMarceddu SalvatoreSanna VannaRoggio AnnaUzzau Sergio<p>Abstract</p> <p>Docetaxel (Dtx) chemotherapy is the optional treatment in patients with hormone-refractory metastatic prostate cancer, and Dtx-loaded polymeric nanoparticles (NPs) have the potential to induce durable clinical responses. However, alternative formulations are needed to overcome the serious side effects, also due to the adjuvant used, and to improve the clinical efficacy of the drug.</p> <p>In the present study, two novel biodegradable <it>block</it>-copolymers, poly(lactide-co-caprolactone) (PLA-PCL) and poly(lactide-co-caprolactone-co-glycolide) (PLGA-PCL), were explored for the formulation of Dtx-loaded NPs and compared with PLA- and PLGA-NPs. The nanosystems were prepared by an original nanoprecipitation method, using Pluronic F-127 as surfactant agent, and were characterized in terms of morphology, size distribution, encapsulation efficiency, crystalline structure, and <it>in vitro </it>release. To evaluate the potential anticancer efficacy of a nanoparticulate system, <it>in vitro </it>cytotoxicity studies on human prostate cancer cell line (PC3) were carried out. NPs were found to be of spherical shape with an average diameter in the range of 100 to 200 nm and a unimodal particle size distribution. Dtx was incorporated into the PLGA-PCL NPs with higher (<it>p </it>&lt; 0.05) encapsulation efficiency than that of other polymers. Differential scanning calorimetry suggested that Dtx was molecularly dispersed in the polymeric matrices. <it>In vitro </it>drug release study showed that release profiles of Dtx varied on the bases of characteristics of polymers used for formulation. PLA-PCL and PLGA-PCL drug loaded NPs shared an overlapping release profiles, and are able to release about 90% of drug within 6 h, when compared with PLA- and PLGA-NPs. Moreover, cytotoxicity studies demonstrated advantages of the Dtx-loaded PLGA-PCL NPs over pure Dtx in both time- and concentration-dependent manner. In particular, an increase of 20% of PC3 growth inhibition was determined by PLGA-PCL NPs with respect to free drug after 72 h incubation and at all tested Dtx concentration. In summary, PLGA-PCL copolymer may be considered as an attractive and promising polymeric material for the formulation of Dtx NPs as delivery system for prostate cancer treatment, and can also be pursued as a validated system in a more large context.</p>http://www.nanoscalereslett.com/content/6/1/260
spellingShingle Sechi Mario
Posadino Anna
Cossu Annalisa
Pintus Gianfranco
Mariani Alberto
Alzari Valeria
Marceddu Salvatore
Sanna Vanna
Roggio Anna
Uzzau Sergio
Novel docetaxel-loaded nanoparticles based on poly(lactide-co-caprolactone) and poly(lactide-co-glycolide-co-caprolactone) for prostate cancer treatment: formulation, characterization, and cytotoxicity studies
Nanoscale Research Letters
title Novel docetaxel-loaded nanoparticles based on poly(lactide-co-caprolactone) and poly(lactide-co-glycolide-co-caprolactone) for prostate cancer treatment: formulation, characterization, and cytotoxicity studies
title_full Novel docetaxel-loaded nanoparticles based on poly(lactide-co-caprolactone) and poly(lactide-co-glycolide-co-caprolactone) for prostate cancer treatment: formulation, characterization, and cytotoxicity studies
title_fullStr Novel docetaxel-loaded nanoparticles based on poly(lactide-co-caprolactone) and poly(lactide-co-glycolide-co-caprolactone) for prostate cancer treatment: formulation, characterization, and cytotoxicity studies
title_full_unstemmed Novel docetaxel-loaded nanoparticles based on poly(lactide-co-caprolactone) and poly(lactide-co-glycolide-co-caprolactone) for prostate cancer treatment: formulation, characterization, and cytotoxicity studies
title_short Novel docetaxel-loaded nanoparticles based on poly(lactide-co-caprolactone) and poly(lactide-co-glycolide-co-caprolactone) for prostate cancer treatment: formulation, characterization, and cytotoxicity studies
title_sort novel docetaxel loaded nanoparticles based on poly lactide co caprolactone and poly lactide co glycolide co caprolactone for prostate cancer treatment formulation characterization and cytotoxicity studies
url http://www.nanoscalereslett.com/content/6/1/260
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