Delivery and Effectiveness of Carboplatin via Targeted Delivery Compared to Passive Accumulation of Intravenously Injected Particles Releasing Carboplatin upon Irradiation.

ABSTRACT

In this study, nanoparticles that release anticancer drugs upon irradiation were developed. Here, MM46 and MM48 tumors in C3He/N mice were irradiated. Furthermore, the intravenously (i.v.) injected nanoparticles were tested for their ability to deliver the anticancer drug, increase the antitumor effect via a synergistic effect of combining targeted anticancer drugs with radiation and decrease adverse effects by localizing the anticancer drug. The nanoparticles were prepared by spraying a mixture of hyaluronic acid and alginate, supplemented with carboplatin, into a solution of CaCl2 and FeCl2 through a 0.8-lm-pore stainless mesh filter. Nanoparticles (1 × 1010) were i.v. injected and irradiated (100-KeV soft X rays, 10-40 Gy) when the accumulation of particles peaked. The nanoparticles were 547 ± 43 nm in diameter. The i.v.-injected nanoparticles accumulated around tumors. Maximum accumulations were observed 9 h post-injection. Subsequently, 10-40 Gy of radiation was administered. The accumulated nanoparticles released the carboplatin and gelatinized their outer shells, which prolonged the intra-tumor concentration of carboplatin and increased the radiation-induced synergistic antitumor effect. The localization of carboplatin by nanoparticles significantly reduced the adverse effects of the anticancer drug.