Toxicity of Drugs Associated with Poly Alkyl Cyanoacrylate Nanoparticles

The study of the acute toxicity of doxorubicin associated with polysorbate 80-coated nanoparticles in healthy rats and rats with intracranially implanted 101/8 glioblastoma was reported by Gelperina et al.111 Single intravenous administration of empty PBCA nanoparticles in the dose range of 100400 mg/kg did not cause mortality within the period of observation and also did not affect body weight or the weight of the internal organs. Association of doxorubicin with PBCA nanoparticles did not produce significant changes of quantitative parameters of acute toxicity of the antitumor agent. Efficacy and toxicity of mitoxantrone-loaded PACA nanoparticles were compared with a drug solution and with a mitoxantrone-liposome formulation.89 Furthermore, the influence of an additional coating surfactant, poloxamine 1508, which has been shown to change the body distribution of other polymeric nanoparticles, was investigated. PACA nanoparticles led to a significant reduction in tumor volume of B-16 melanoma in mice compared to liposomes. However, neither nanoparticles nor liposomes had overcome the mitoxantrone-associated leucocytopenia.

In a study by Gibaud et al.122 involving the determination of the myelosuppressive effects of free and PACA-bound doxorubicin in mice in vivo, the alkyl cyanoacrylate nanoparticle-bound doxorubicin showed the highest myelosuppressive effect. The total and differential counts of blood, bone marrow, and spleen cells, as well as the number of granulocyte progenitors (CFU-GM), was determined by culture after the intravenous injection of 11 mg/kg body weight of doxorubicin, either free or bound to PIBCA or PIHCA nanoparticles. Doxorubcin bound to PIHCA nanoparticles showed the highest and longest myelosuppressive effects, which correlated well with a high concentration of the drug in the bone marrow and spleen. Furthermore, the PIHCA nanoparticles induced the release of colony-stimulating factors, which might account for the observed increase in the toxic effects of doxorubicin on bone marrow progenitors.

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