Reversed lipid-based nanoparticles dispersed in oil for malignant tumor treatment via intratumoral injection.

Intratumoral injection of anticancer drugs directly delivers chemotherapeutics to the tumor region, offering an alternative strategy for cancer treatment. However, most hydrophilic drugs spread quickly from the injection site into systemic circulation, leading to inferior antitumor activity and adverse effects in patients. Therefore, we developed novel reversed lipid-based nanoparticles (RLBN) as a nanoscale drug carrier. RLBNs differ from traditional nanoscale drug carriers in that they possess a reversed structure consisting of a polar core and lipophilic periphery, leading to excellent solubility and stability in hydrophobic liquids; therefore, hydrophilic drugs can be entrapped in RLBNs and dispersed in oil. In vivo studies in tumor-bearing Balb/c nude mice indicated remarkable antitumor activity of RLBN-DOX after a single injection, with effective tumor growth inhibition for at least 17 days; the inhibition rate was ∼80%. These results can be attributed to the long-term retention and sustained drug release of RLBN-DOX in the tumor region. In contrast, intratumoral injection of free DOX showed weaker antitumor activity than RLBN-DOX did, with the tumor size doubling by day 11 and tripling by day 17. Further, the initial burst of drug released from free DOX could produce detrimental systemic effects, such as weight loss. Histological analyses by TUNEL staining showed apoptosis after treatment with RLBN-DOX, whereas tumor cell viability was high in the free DOX group. Current results indicate that RLBNs show sustained delivery of hydrophilic agents to local areas resulting in therapeutic efficacy, and they may be a promising drug delivery system suitable for intratumoral chemotherapy.