Preparation, characterisation and preliminary antitumour activity evaluation of a novel nanoparticulate system based on a cisplatin-hyaluronate complex and N-trimethyl chitosan

Abstract

In this work, nanoparticles with a positive surface charge were prepared through the electrostatic interaction of a new cisplatin-hyaluronate complex with N-trimethyl chitosan (substitution degree of 85%). Mean particle diameter was approximately 195 nm. Drug loading of nanoparticles, which had a zeta potential of about 27 mV, was equal to 6% w/w. After 24 h, while the cisplatin-hyaluronate complex released approximately 60% w/w drug in phosphate buffered saline at pH 7.4, approximately 40% w/w of total cisplatin was released from nanoparticles. The same cumulative amounts of released drug were found after 48 h. These nanoparticles, as well as the starting cisplatin-hyaluronate complex, were active on all cell lines tested (P388, A2780, A549), with an antiproliferative activity similar to that of cisplatin. Apoptosis was markedly induced in A2780 cells by nanoparticles. In a preliminary in vivo experiment, the antitumour activity against a murine tumour (P388 cells) subcutaneously implanted in mice, resulted similar to that of cisplatin for nanoparticles whereas the starting complex showed a non-significant activity at the cisplatin dose tested. Body weight change of treated mice suggested a significantly better tolerance of the nanoparticles compared to cisplatin, after an initial brief period of acute toxicity higher than the parent drug. These results indicate that such a particulate system could be useful as a carrier for cisplatin delivery.

Carbohydrate-based nanocarriers and their application to target macrophages and deliver antimicrobial agents

“…[56,135] Cafaggi et al obtained GNPs by PEC of a cisplatinhyaluronate complex with a modified chitosan and found a mean particle size of approximately 195 nm. [141] More recently, Ramasamy and co-workers developed layer-bylayer (LBL) method to produce GNPs through a sequential deposition of chitosan and HA on negatively charged hybrid solid lipid nanoparticles (SLNs) for drug delivery to tumour cells (Figure 7). [142] The reported GNPs (ca.…”

Novel nanoparticle materials for drug/food delivery-polysaccharides

“…Hyaluronic acid (HA) (also called hyaluronan, hyaluronate) is an anionic polysaccharide composed of repeating disaccharide units of D-glucuronic acid and N -acetyl D-glucosamine linked via altering β-1,3 andβ-1,4 glycosidic bonds as shown in Figure 10 [135]. HA has been reported to associate with several cellular processes, including angiogenesis and the regulation of inflammation [136].…”

Nanoparticles Based on Chitosan Derivatives

“…To this purpose N-carboxymethyl chitosan, poly(γ-glutamic acid), poly(aspartic acid) and hyaluronic acid were used as polyanions, while TMC and glycidyl trimethyl ammonium chitosan were the polycations [24][25][26][27]. In a case both the polyanion (hyaluronic acid) and the polycation (TMC) were thiolated and the nanoparticles were stabilized by the formation of interchain disulfide bonds [28].…”