Influence of polybutylcyanoacrylate nanoparticles and liposomes on the efficacy and toxicity of the anticancer drug mitoxantrone in murine tumour models

Abstract

Polybutylcyanoacrylate (PBCA) nanoparticles were prepared and loaded with mitoxantrone, a highly effective anticancer drug. The proportion of mitoxantrone bound to the particles was analysed to be about 15 per cent of the initial drug concentration with the incorporation method and about 8 per cent with the adsorption method. Selected nanoparticle formulations were tested in leukaemia- or melanoma-bearing mice after intravenous injection. Efficacy and toxicity of mitoxantrone nanoparticles were compared with a drug solution and with a mitoxantrone-liposome formulation (small unilamellar vesicles with a negative surface charge). Furthermore, influence of an additional coating surfactant, poloxamine 1508, which has been shown to change body distribution of other polymeric nanoparticles, was investigated. It was shown that PBCA nanoparticles and liposomes influenced the efficacy of mitoxantrone in cancer therapy differently: liposomes prolonged survival time in P388 leukaemia, whereas nanoparticles led to a significant tumour volume reduction at the B16 melanoma. Neither nanoparticles nor liposomes were able to reduce the toxic side-effects caused by mitoxantrone, namely leucocytopenia. A slight additional influence of the coating surfactant was observed with only one preparation.

Polymeric Nanoparticles Containing Combination Antiretroviral Drugs for HIV Type 1 Treatment

“…[18][19][20] Nanoparticles have been reported to concentrate in tumor masses, inflammatory sites, and infection sites. 21 Nanotechnology has been considered for the delivery of antimicrobial agents, including antiretroviral agents, for more than a decade.…”

Biocompatible Nanoparticulate Systems for Tumor Diagnosis and Therapy

“…Some studies on nanoparticle-bound antitumor agents have indicated that nanoparticles can prolong the retention of the drug by tumors, reduce tumor growth and prolong the survival of tumor-bearing animals [30,[35][36][37].…”

Drug targeting with nanoparticles

“…The reason for this could be the high leakyness of tumor blood vessels and a possible higher endocytotic activity of tumor-associated cells in the blood vessels or in their vincinity. Nanoparticles of a number of antitumor drugs (17)(18)(19)(20). Although in some cases (17, (9) the enhanced effiacy also were able to considerably enhance the efficacy was accompanied with an increase in toxicity, in other cases even a decrease in tocixity was observed (21,22).…”

“…Recent results with mitoxantrone showed that the efficacy against different types of tumors may be dependent on the delivery system (20). Mitoxantrone nanoparticles made of poly(butyl cyanoacrylate) were more effective against a solid B 16 melanoma tumor, whereas mitoxantrone liposomes were more effective against P 388 leucemia.…”