Nanoemulsion loaded with lycobetaine–oleic acid ionic complex: physicochemical characteristics, in vitro, in vivo evaluation, and antitumor activity

BACKGROUND: Intravenous injection of lycobetaine was found to show significant cytotoxic activity against (inter alia) Lewis lung carcinoma, but its therapeutic use is largely limited due to an extremely short half-life in blood. This study aimed at developing a novel lipid nanocarrier-based formulation for lycobetaine delivery. The formulation is feasible for scale-up production, exhibiting good parenteral acceptability and improved circulation characteristics. METHODS: To enhance its lipophilicity, oleic acid was selected to form ionic complexes with lycobetaine (LBT). The nanoemulsion loaded with LBT–oleic acid complex (LBT–OA–nanoemulsion) and PEGylated LBT–OA–nanoemulsion (NE) (LBT–OA–PEG–NE) were prepared by a simple high-pressure homogenization method. RESULTS: A high-encapsulation efficiency of around 97.32% ± 2.09% was obtained for LBT–OA–PEG–NE under optimized conditions. Furthermore, the in vivo pharmacokinetics and biodistribution of LBT–OA–NE, LBT–OA–PEG–NE, and free LBT were studied in rats. Free LBT and LBT–OA–PEG–NE displayed AUC(0–10h) (area under the concentration-time curve from 0 to 10 hours) of 112.99 mg/L*minute and 3452.09 mg/L*minute via intravenous administration (P < 0.005), respectively. Moreover, LBT–OA–PEG–NE showed significantly lower LBT concentration in the heart, liver, and kidney, while achieving higher concentration of LBT in the lung when compared to free LBT at the same time (P < 0.005). The LBT–OA–PEG–NE exhibited higher growth inhibitory effect and longer survival time than free LBT in both heterotopic and lung metastatic tumor models. CONCLUSION: These results demonstrated that LBT–OA–PEG–NE is an attractive parenteral formulation for cancer therapy.