Zoledronic acid (ZOL) is a drug whose potent anti-cancer activity is limited by their short plasma half-life and rapid uptake and accumulation within bone1. We have recently proposed new delivery systems to avoid ZOL accumulation into the bone, thus improving extra-skeletal bioavailability. In this work, we have compared the technological and anti-cancer features of either ZOL-containing self-assembly PEGylated nanoparticles (NPs)2 or ZOL-encapsulating PEGylated liposomes (LIPO-ZOL)3. ZOL-containing NPs showed superior technological characteristics in terms of mean diameter, size distribution, and ZOL encapsulation efficiency, compared to LIPO-ZOL. Moreover, the anti-cancer activity of NPs in nude mice xenografted with prostate cancer PC3 cells was higher than that one induced by LIPO-ZOL (figure1). In addition, NPs induced the complete remission of tumour xenografts and an increase of survival time higher than that one observed with LIPO-ZOL. It has also to be considered that PC3 tumour xenografts were almost completely resistant to the anti-cancer effects induced by free ZOL. Both nanotechnological products did not induced toxic effects not affecting the mice weight nor inducing deaths. Moreover, the histological examination of some vital organs such as liver, kidney and spleen did not find any changes in terms of necrotic effects or modifications in the inflammatory infiltrate. On the other hand, NPs but not LIPO-ZOL caused a statistically significant reduction of the tumour associated macrophages (TAM) in tumour xenografts. This effect was paralleled by a significant increase of both necrotic and apoptotic indexes. The effects of the two nanotechnological agents were, on the other hand, similar in terms of neo-angiogenesis inhibition. These results suggest the future preclinical development of ZOL-encapsulating NPs in the treatment of human cancer.
New self-assembly nanoparticles and stealth liposomes for the delivery of zoledronic acid: a comparative study / DE ROSA, Giuseppe; Salzano, Giuseppina; M., Marra; C., Leonetti; M., Porru; R., Franco; S., Zappavigna; G., Liguori; G., Botti; A., Abbruzzese; M. C. a. r. a. g. l. i., A.. - (2011), pp. 0-0. (Intervento presentato al convegno NANODRUG 2011 tenutosi a Roma nel 10-13 ottobre 2011).
New self-assembly nanoparticles and stealth liposomes for the delivery of zoledronic acid: a comparative study.
DE ROSA, GIUSEPPE;SALZANO, GIUSEPPINA;
2011
Abstract
Zoledronic acid (ZOL) is a drug whose potent anti-cancer activity is limited by their short plasma half-life and rapid uptake and accumulation within bone1. We have recently proposed new delivery systems to avoid ZOL accumulation into the bone, thus improving extra-skeletal bioavailability. In this work, we have compared the technological and anti-cancer features of either ZOL-containing self-assembly PEGylated nanoparticles (NPs)2 or ZOL-encapsulating PEGylated liposomes (LIPO-ZOL)3. ZOL-containing NPs showed superior technological characteristics in terms of mean diameter, size distribution, and ZOL encapsulation efficiency, compared to LIPO-ZOL. Moreover, the anti-cancer activity of NPs in nude mice xenografted with prostate cancer PC3 cells was higher than that one induced by LIPO-ZOL (figure1). In addition, NPs induced the complete remission of tumour xenografts and an increase of survival time higher than that one observed with LIPO-ZOL. It has also to be considered that PC3 tumour xenografts were almost completely resistant to the anti-cancer effects induced by free ZOL. Both nanotechnological products did not induced toxic effects not affecting the mice weight nor inducing deaths. Moreover, the histological examination of some vital organs such as liver, kidney and spleen did not find any changes in terms of necrotic effects or modifications in the inflammatory infiltrate. On the other hand, NPs but not LIPO-ZOL caused a statistically significant reduction of the tumour associated macrophages (TAM) in tumour xenografts. This effect was paralleled by a significant increase of both necrotic and apoptotic indexes. The effects of the two nanotechnological agents were, on the other hand, similar in terms of neo-angiogenesis inhibition. These results suggest the future preclinical development of ZOL-encapsulating NPs in the treatment of human cancer.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
