Interactions of cisplatin with calcium phosphate nanoparticles: In vitro controlled adsorption and release

Abstract

A new system for the local delivery of chemotherapy to malignant solid tumors has been developed based on calcium phosphate (Cap) nanoparticles. The adsorption of the anti-neoplastic drug cis-diamminedichloroplatinum (cisplatin) was characterized on three types of apatitic CaP (poorly and well crystallized hydroxyapatite, and carbonated apatite). Adsorption isotherms obtained in chloride-free phosphate solutions at pH = 7.4 (24 and 37 "C) indicate that cisplatin adsorption increases with temperature and increases with decreasing crystallinity. Release studies in phosphate buffer saline (containing the chloride ion essential for release)showed that while the cumulative amount of released drug was the same for all apatites at 20 days (-70'%1 of the total bound), the least crystalline material released the drug more slowly. The drug release rate increased slightly with temperature. Cytotoxicity testing was conducted in a K8 clonal murine osteosarcoma cell line to verify that drug activity was retained after adsorption onto the apatite crystals. K8 cells were plated onto dried films of the apatitekisplatin conjugates and after 24 h, viability was measured with tritiated uridine. The apatitekisplatin formulations exhibited cytotoxic effects with a dose dependent diminishment of cell viability.

The Biomimetic Approach to Design Apatites for Nanobiotechnological Applications

“…They can only be displaced by mineral ions and/or soluble proteins with a stronger affinity for apatite surfaces but in a predicable manner, or by cell activity (Errassif et al, 2010). This characteristic has been observed for various growth factors like bone morphogenetic protein (BMP-2) or vascular endothelial growth factor (VEGF) (Midy et al, 2001;Boix et al, 2005), antiosteoporisis agents (Yoshinari et al, 2001;McLeod et al, 2006) and anticancer drugs as methotraxate and cisplatin (Barroug et al, 2004;Lebugle et al, 2002). It has been reported that slow release of MTX from calcium phosphate is not only due to the porosity like in most of the cases, but mainly due to the adsorption of MTX (Lebugle et al, 2002).…”

Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration

“…BPs and DXR are not the only drugs used to treat bone metastasis; other chemotherapeutic drugs, such as cisplatin, can also be used. NP deliveries of these drugs have been demonstrated to increase treatment efficacy in vitro; 42,43 however, in vivo model testing is still necessary to validate these delivery systems.…”

“…45 Besides, magnetic arsenic trioxide NPs were shown to have targeted effects on osteosarcoma cells by applying a magnetic field, 46 while calcium phosphate NPs were shown to be able to deliver the anticancer drug, cisplatin, and exhibit cytotoxic effects to a murine osteosarcoma cell line (K8) in a dose-dependent manner. 43 For the general treatment of osteosarcoma, Susa et al 42 reported biocompatible, lipid-modified, dextran-based polymeric NPs and showed that the NPs loaded with DXR had a curative effect on multidrug resistant osteosarcoma cells by increasing the amount of drug accumulation in the nucleus, and increased apoptosis in osteosarcoma cells as compared with DXR alone. Similarly, Sun et al 47 showed a combined strategy of chemotherapy and gene therapy in a single dextran-polyethylenimine (PEI)-NP.…”

Multifunctional Nanocomposites Based on Mesoporous Silica: Potential Applications in Biomedicine

“…Besides the polymeric matrix, other controlled release systems based on different materials have been intensively studied in recent years, such as bioceramic and composites. Some examples are antibiotics like gentamicin, released from the matrix composed of calcium phosphates and poly(DL-lactide) (PLA) (Baro et al, 2002) and from the composite of hydroxyapatite/collagen (Martins & Goissis, 2000), and antineoplastic agents like cisplatin, released from calcium phosphate (CaP) nanoparticles (Barroug et al, 2004). The porosity of conventional matrices is highly heterogeneous due to complex chemical composition, which presents as a great disadvantage the difficulty of ensuring homogeneous drug distribution through the matrix, affecting the release rate.…”