Preparation, characterisation and preliminary antitumour activity evaluation of a novel nanoparticulate system based on a cisplatin-hyaluronate complex and N-trimethyl chitosan.
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.
Cafaggi
Sergio
S
Dipartimento di Chimica e Tecnologie Farmaceutiche ed Alimentari, Via Brigata Salerno 13, 16147, Genoa, Italy. cafaggi@dictfa.unige.it
Russo
Eleonora
E
Stefani
Rossana
R
Parodi
Brunella
B
Caviglioli
Gabriele
G
Sillo
Greta
G
Bisio
Angela
A
Aiello
Cinzia
C
Viale
Maurizio
M
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan / Q000494:pharmacology*; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology*; D004058:Diffusion / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D012044:Regression Analysis; D047368:Tumor Burden / Q000187:drug effects
D000970:Antineoplastic Agents; C118071:N-trimethyl chitosan chloride; D006820:Hyaluronic Acid; D048271:Chitosan; D002945:Cisplatin