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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.

Sanna V, Roggio AM, Posadino AM, Cossu A, Marceddu S, Mariani A, Alzari V, Uzzau S, Pintus G, Sechi M - Nanoscale Res Lett (2011)

Bottom Line: 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.In the present study, two novel biodegradable block-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.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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Porto Conte Ricerche, Località Tramariglio, Alghero, Sassari 07041, Italy. sannav@portocontericerche.it.

ABSTRACT
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.In the present study, two novel biodegradable block-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 in vitro release. To evaluate the potential anticancer efficacy of a nanoparticulate system, in vitro 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 (p < 0.05) encapsulation efficiency than that of other polymers. Differential scanning calorimetry suggested that Dtx was molecularly dispersed in the polymeric matrices. In vitro 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.

No MeSH data available.


Related in: MedlinePlus

In vitro release profiles of Dtx-loaded PLA, PLGA, PLA-PCL, and PLGA-PCL NPs.
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Figure 4: In vitro release profiles of Dtx-loaded PLA, PLGA, PLA-PCL, and PLGA-PCL NPs.

Mentions: The cumulative percentages of Dtx released from NPs based on different polymers as a function of time are reported in Figure 4. All formulations are characterized by similar release profiles, but the release rate is strongly affected by the properties of the polymer matrix. In particular, PLA-based NPs are characterized by the slower release (only about 60% of Dtx is released within 6 h) that can be attributed to the stronger hydrophobic interaction between hydrophobic domain of PLA and drug. Due to the presence of the hydrophilic glycolide units into the PLA polymer (50:50 molar ratio), in the case of NPs formulated with PLGA a completed dissolution of Dtx is achieved within the first 2 hof the test. In fact, the higher hydrophilicity of copolymer improved the water permeability into NPs with a more rapid drug diffusion as well as a faster degradation of the polymer [8]. As for PCL copolymers, the diffusion rate of drug from PLA-PCL NPs is higher at the first 2 h and levelled off after 3 h of the test, thus resulting almost superimposed to those of PLGA-PCL formulations. These results can be related to the similar composition of PLA-PCL and PLGA-PCL copolymers containing a lactide:caprolactone 70:30 and lactide:glycolide:caprolactone 70:10:20 molar ratio, respectively. Moreover, with respect to PLGA, a significant retard on dissolution rate of Dtx from PLGA-PCL NPs alone was obtained, whereas an opposite effect is observed in the case of PLA-PCL copolymer compared to PLA-NPs. Furthermore, with respect to PLA homopolymer, the more hydrophilic block of caprolactone of PLA-PCL copolymer-based NPs leads to a significant improvement of Dtx released (85%, during the 6 h). A complete release of Dtx is obtained for all samples after 24 h of the test.


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.

Sanna V, Roggio AM, Posadino AM, Cossu A, Marceddu S, Mariani A, Alzari V, Uzzau S, Pintus G, Sechi M - Nanoscale Res Lett (2011)

In vitro release profiles of Dtx-loaded PLA, PLGA, PLA-PCL, and PLGA-PCL NPs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3211323&req=5

Figure 4: In vitro release profiles of Dtx-loaded PLA, PLGA, PLA-PCL, and PLGA-PCL NPs.
Mentions: The cumulative percentages of Dtx released from NPs based on different polymers as a function of time are reported in Figure 4. All formulations are characterized by similar release profiles, but the release rate is strongly affected by the properties of the polymer matrix. In particular, PLA-based NPs are characterized by the slower release (only about 60% of Dtx is released within 6 h) that can be attributed to the stronger hydrophobic interaction between hydrophobic domain of PLA and drug. Due to the presence of the hydrophilic glycolide units into the PLA polymer (50:50 molar ratio), in the case of NPs formulated with PLGA a completed dissolution of Dtx is achieved within the first 2 hof the test. In fact, the higher hydrophilicity of copolymer improved the water permeability into NPs with a more rapid drug diffusion as well as a faster degradation of the polymer [8]. As for PCL copolymers, the diffusion rate of drug from PLA-PCL NPs is higher at the first 2 h and levelled off after 3 h of the test, thus resulting almost superimposed to those of PLGA-PCL formulations. These results can be related to the similar composition of PLA-PCL and PLGA-PCL copolymers containing a lactide:caprolactone 70:30 and lactide:glycolide:caprolactone 70:10:20 molar ratio, respectively. Moreover, with respect to PLGA, a significant retard on dissolution rate of Dtx from PLGA-PCL NPs alone was obtained, whereas an opposite effect is observed in the case of PLA-PCL copolymer compared to PLA-NPs. Furthermore, with respect to PLA homopolymer, the more hydrophilic block of caprolactone of PLA-PCL copolymer-based NPs leads to a significant improvement of Dtx released (85%, during the 6 h). A complete release of Dtx is obtained for all samples after 24 h of the test.

Bottom Line: 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.In the present study, two novel biodegradable block-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.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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Porto Conte Ricerche, Località Tramariglio, Alghero, Sassari 07041, Italy. sannav@portocontericerche.it.

ABSTRACT
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.In the present study, two novel biodegradable block-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 in vitro release. To evaluate the potential anticancer efficacy of a nanoparticulate system, in vitro 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 (p < 0.05) encapsulation efficiency than that of other polymers. Differential scanning calorimetry suggested that Dtx was molecularly dispersed in the polymeric matrices. In vitro 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.

No MeSH data available.


Related in: MedlinePlus