Preparation and evaluation of nanoparticles made of chitosan or N-trimethyl chitosan and a cisplatin-alginate complex.
In this work, nanoparticles with a negative or positive surface charge were prepared through electrostatic interaction of an anionic cisplatin-alginate complex with a cationic polyelectrolyte, namely chitosan or N-trimethyl chitosan (substitution degree of 85%). Statistical experimental design allowed the study of the influence of component amounts on the characteristics of nanoparticles. Mean particle diameter ranged from 180 nm to 350 nm. After 24 h, while the cisplatin-alginate complex released almost all the drug in saline-buffered solution at pH 7.4, approximately 40% w/w of total cisplatin was released from negative nanoparticles and roughly 50% w/w from positive ones. The same cumulative amounts of released drug were found after 48 h, with a progressive reduction to lower values up to 6 days. Drug loading of nanoparticles with a positive zeta potential (43 mV-60 mV) ranged from 13% w/w to 21% w/w and particle yield, referred to total polymers, was about 15% w/w (50% w/w if referred to cisplatin-alginate complex). Nanoparticles with a negative zeta potential (-34 mV) were obtained with a yield of 40% w/w and a drug loading of 18% w/w. These nanoparticles were the least active on all cell lines tested, while the cytotoxic activity of the positive nanoparticles was similar to or lower than that of cisplatin, probably depending on the combination of sizes and zeta potential values, on P388 murine and A2780 human cells. On A549 human cells, the nanoparticles with the smallest size and the lowest positive zeta potential were more active than cisplatin and showed a similar capability in inducing apoptosis in A2780 human cells. These results indicate that cisplatin complexes with polycarboxylate polymers can be transformed into cisplatin particulate carriers of high potential interest.
Cafaggi
S
S
Dipartimento di Chimica e Tecnologie Farmaceutiche ed Alimentari, via Brigata Salerno 13, 16147 Genova, Italy. cafaggi@dictfa.unige.it <cafaggi@dictfa.unige.it>
Russo
E
E
Stefani
R
R
Leardi
R
R
Caviglioli
G
G
Parodi
B
B
Bignardi
G
G
De Totero
D
D
Aiello
C
C
Viale
M
M
D000464:Alginates / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000032:analysis / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002021:Buffers; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D002945:Cisplatin / Q000032:analysis / Q000737:chemistry* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D020723:Glucuronic Acid / Q000737:chemistry / Q000494:pharmacology; D006603:Hexuronic Acids / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007938:Leukemia / Q000473:pathology; D008175:Lung Neoplasms / Q000473:pathology; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010051:Ovarian Neoplasms / Q000473:pathology; D010316:Particle Size; D055672:Static Electricity
D000464:Alginates; D000970:Antineoplastic Agents; D002021:Buffers; D006603:Hexuronic Acids; D020723:Glucuronic Acid; D048271:Chitosan; D002945:Cisplatin