Safety evaluation of nanodiamond-doxorubicin complexes in a Naive Beagle canine model using hematologic, histological, and urine analysis

While doxorubicin (DOX) is one of the most common chemotherapeutic drugs for treating cancer, use of DOX must be managed carefully due to dose-related toxicity. Nanodiamond (ND) drug delivery system conjugated with DOX (NDX) has been reported to enhance treatment efficacy and attenuate toxicity in murine cancer models. In addition, extensive biocompatibility studies indicate that NDs seem to be well tolerated in non-human primates. Before the clinical translation of NDX, it is necessary to verify the safety of ND in large mammals. Studies of nanomedicine drug safety for large animal are not commonly reported, and this work represents a key milestone in bridging earlier advances towards clinical assessment. Herein, NDs' safety as a drug-delivery platform was evaluated in Naive Beagle dogs. The study is performed with DOX, ND, and NDX in a dual-gender animal model using intravenous (IV) injection and hepatic portal vein (HPV) injection methods. The dogs are monitored for their health phenotype changes in continuous 5 days. Blood and urine obtained are for clinical pathology research. The results indicate that ND drug delivery platform significantly relieves DOX toxicity for Naive Beagle dog model. This study provides guidance for the pre-clinical safety assessment of NDX therapy at large animal level.

Automated summary

This study evaluated the safety of nanodiamonds (ND) as a drug-delivery platform in Naive Beagle dogs, showing that the ND drug delivery platform significantly reduces doxorubicin (DOX) toxicity in the Naive Beagle dog model.