Nanomedicine applied to cancer therapy has provide a wide range of new delivery systems able to target tumor cells. However, there is a recognized need to improve the design and development of nanocarriers that should be able to improve the therapeutic benefits of oncologicals [1]. Among the biomaterials used in the development of nanomedicines, polysaccharides as hyaluronic acid (HA), and polyaminoacids as poly(L-arginine) (PArg) have raised great expectancy because of their biodegradability and acceptable regulatory profile [2]. The aim of the work presented here has been to formulate a new type of polymeric nanostructures made of HA and PArg for the encapsulation of pentamidine. Recent works showed that pentamidine has a strong antiproliferative effect both in in-vitro and in-vivo models of solid tumors [3-5]. Despite its already proven efficacy, the systemic administration of pentamidine is compromised by its serious toxicities, particularly renal [6]. Thus, to overcome this problem and to enhance the uptake by cancer cells, a new drug delivery system has been developed. Moreover, HA based carrier could also increase the cellular uptake of the drug thanks to the presence of a specific HA receptor namely CD44, overexpressed on human cancer cells. Using ionic gelation technique we obtained biocompatible nanoparticles with an average size between 150 nm and 200 nm and a negative zeta potential, around -30 mV. We optimized the system in order to load pentamidine which was associated in a high amount (79 %). Morphological analysis carried out using transmission electron microscopy (TEM) shown a monodispersed population with a round regular shape. Moreover, these particles were lyophilized in order to improve their stability. After resuspension the nanoparticles recovered their initial physicochemical properties in terms of size and association efficiency. In vitro viability studies performed on A549 lung and MDA-MB-231 human breast cancer cell lines evidenced that PTM-loaded nanoparticles have a similar effect on the reduction of cell viability while blank nanoparticles were not toxic.
Nanotechnological strategies for pentamidine delivery in cancer treatment
F. Carton;
2018-01-01
Abstract
Nanomedicine applied to cancer therapy has provide a wide range of new delivery systems able to target tumor cells. However, there is a recognized need to improve the design and development of nanocarriers that should be able to improve the therapeutic benefits of oncologicals [1]. Among the biomaterials used in the development of nanomedicines, polysaccharides as hyaluronic acid (HA), and polyaminoacids as poly(L-arginine) (PArg) have raised great expectancy because of their biodegradability and acceptable regulatory profile [2]. The aim of the work presented here has been to formulate a new type of polymeric nanostructures made of HA and PArg for the encapsulation of pentamidine. Recent works showed that pentamidine has a strong antiproliferative effect both in in-vitro and in-vivo models of solid tumors [3-5]. Despite its already proven efficacy, the systemic administration of pentamidine is compromised by its serious toxicities, particularly renal [6]. Thus, to overcome this problem and to enhance the uptake by cancer cells, a new drug delivery system has been developed. Moreover, HA based carrier could also increase the cellular uptake of the drug thanks to the presence of a specific HA receptor namely CD44, overexpressed on human cancer cells. Using ionic gelation technique we obtained biocompatible nanoparticles with an average size between 150 nm and 200 nm and a negative zeta potential, around -30 mV. We optimized the system in order to load pentamidine which was associated in a high amount (79 %). Morphological analysis carried out using transmission electron microscopy (TEM) shown a monodispersed population with a round regular shape. Moreover, these particles were lyophilized in order to improve their stability. After resuspension the nanoparticles recovered their initial physicochemical properties in terms of size and association efficiency. In vitro viability studies performed on A549 lung and MDA-MB-231 human breast cancer cell lines evidenced that PTM-loaded nanoparticles have a similar effect on the reduction of cell viability while blank nanoparticles were not toxic.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
