TY - JOUR
T1 - Antitumor activity of PEGylated biodegradable nanoparticles for sustained release of docetaxel in triple-negative breast cancer
AU - Palma, Giuseppe
AU - Conte, Claudia
AU - Barbieri, Antonio
AU - Bimonte, Sabrina
AU - Luciano, Antonio
AU - Rea, Domenica
AU - Ungaro, Francesca
AU - Tirino, Pasquale
AU - Quaglia, Fabiana
AU - Arra, Claudio
PY - 2014/10/1
Y1 - 2014/10/1
N2 - With the aim to find novel therapeutical approaches for triple-negative breast cancer (TNBC) treatment, we have developed a powder for i.v. injection based on cyclodextrins and docetaxel (DTX)-loaded polyethyleneglycol- poly(epsilon-caprolactone) nanoparticles (DTX-NPs). Nanoparticles are designed to concentrate at tumor level by enhanced permeability and retention effect and release drug cargo at a sustained rate in the blood and in tumor interstitium. DTX-NPs of around 70 nm, shielding proteins and allowing a sustained DTX release for about 30 days, were produced by melting sonication technique. DTX-NPs were associated to hydroxypropyl-β-cyclodextrin to give a powder for injection with excellent dispersibility and suitable for i.v. administration. DTX-NPs were as efficient as free DTX in inhibiting cell growth of MDA-MB231 cells, even at low concentrations, and displayed a comparable in vivo antitumor efficacy and better survival in a TNBC animal model as compared with DTX commercial formulation (Taxotere®). In conclusion, PEGylated biodegradable DTX-NPs highlighted their potential in the treatment of aggressive TNBC providing a foundation for future clinical studies.
AB - With the aim to find novel therapeutical approaches for triple-negative breast cancer (TNBC) treatment, we have developed a powder for i.v. injection based on cyclodextrins and docetaxel (DTX)-loaded polyethyleneglycol- poly(epsilon-caprolactone) nanoparticles (DTX-NPs). Nanoparticles are designed to concentrate at tumor level by enhanced permeability and retention effect and release drug cargo at a sustained rate in the blood and in tumor interstitium. DTX-NPs of around 70 nm, shielding proteins and allowing a sustained DTX release for about 30 days, were produced by melting sonication technique. DTX-NPs were associated to hydroxypropyl-β-cyclodextrin to give a powder for injection with excellent dispersibility and suitable for i.v. administration. DTX-NPs were as efficient as free DTX in inhibiting cell growth of MDA-MB231 cells, even at low concentrations, and displayed a comparable in vivo antitumor efficacy and better survival in a TNBC animal model as compared with DTX commercial formulation (Taxotere®). In conclusion, PEGylated biodegradable DTX-NPs highlighted their potential in the treatment of aggressive TNBC providing a foundation for future clinical studies.
KW - Docetaxel
KW - PEGylated nanoparticles
KW - Powder for injection
KW - Sustained release
KW - Triple-negative breast cancer
UR - http://www.scopus.com/inward/record.url?scp=84903831072&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84903831072&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2014.06.058
DO - 10.1016/j.ijpharm.2014.06.058
M3 - Article
C2 - 24992317
AN - SCOPUS:84903831072
VL - 473
SP - 55
EP - 63
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
IS - 1-2
ER -