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

Liao Shen,Zhen Zhang,Tao Wang,Xi Yang,Ri Huang,Dongqin Quan

doi:10.1080/10717544.2017.1330373

Abstract

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.

Highlights

IntroductionThe most common strategy for this kind of drug is systematic administration, such as intravenous injection (Carter & Soper, 1974; A'Hern et al, 1993)
Hydrophilic anticancer drugs are widely used in the treatment of malignant tumors
Current results indicate that reversed lipid-based nanoparticles (RLBN) 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

Summary

Introduction

The most common strategy for this kind of drug is systematic administration, such as intravenous injection (Carter & Soper, 1974; A'Hern et al, 1993). This route of dosing for chemotherapeutic agents may lead to severe adverse effects such as neutropenia, cardiac toxicity, nausea and vomiting resulting from nonselective damage to both normal and tumor cells (Chari, 2008). Rapid clearance of chemotherapeutics from the blood reduces their anticancer effects (Chun et al, 2009; Al-Abd et al, 2010) For this reason, sustained therapeutic drug concentrations in tumor areas demand repeated chemotherapy in a short time, which strongly increases the associated risks. Preparation of in situ gels usually involves materials that are not commercially available (Jeong et al, 2002; Cao et al, 2007; Moreno et al, 2014; Yu et al, 2017), and the safety of these polymers is still unclear

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Discussion

Conclusion