Improved Targeting and Tumor Retention of a Newly Synthesized Antineoplaston A10 Derivative by Intratumoral Administration: Molecular Docking, Technetium 99m Radiolabeling, and In Vivo Biodistribution Studies.

BACKGROUND: Recently, the direct intratumoral (i.t.) injection of anticancer agents has been investigated. A newly synthesized Antineoplaston A10 analog 3-(4-methoxybenzoylamino)-2,6-piperidinedione (MPD) showed an antitumor activity in human breast cancer cell line. Unfortunately, MPD suffered from poor water solubility.

MATERIALS AND METHODS: Pseudoternary phase diagram of oil (isopropyl myristate), surfactant (Tween 80), cosurfactant (ethanol), and water was plotted. MPD microemulsion (MPDME) was developed and characterized for particle size (PS), polydispersity index (PDI), zeta potential (ZP), and morphology (transmission electron microscopy). MPDME and MPD solution (MPDS) were radiolabeled with technetium 99m (99m Tc) using stannous chloride dihydrate (SnCl2 .2H2 O). Molecular docking of MPD and 99m Tc-MPD was performed to study the interaction with DNA.

RESULTS: The impacts of intravenous (i.v.) and i.t. injections of 99m Tc-MPDME and 99m Tc-MPDS on biodistribution were studied. The developed MPDME showed spherical droplets with mean PS (74.00 ± 5.69 nm), PDI (0.25 ± 0.03), and ZP (33.90 ± 0.90 mV). Labeling yield of 99m Tc-MPDME and 99m Tc-MPDS was 97.00% ± 0.60% and 92.02% ± 0.45%, respectively. MPD and 99m Tc-MPD showed almost same binding affinity with DNA binding site. Biodistribution results showed that i.t. injection of 99m Tc-MPDME significantly enhanced tumor retention compared to i.v. route.

CONCLUSIONS: Herein, the authors concluded that microemulsion could be used as i.t. injectable delivery vehicle to improve targeting and tumor retention of MPD.