mV, respectively, and the encapsulation efficiency and drug loading content were 87.9% and 0.57%. The final concentration of LM was 63.4 μg/mL. The release results showed 58.59% drug was released in 12 h. MTT results showed that the IC50 of LM@Lip on HepG2 and A549 cells was 20.16 and 15.39 μg/mL, respectively, and its in vitro antitumor was superior to that of LM. Conclusion Liposomes can increase the stability and solubility of LM. LM@Lip showed slow-release profile and significant tumor inhibition superior to LM. Key words: limonin; liposomes; thin-film dispersion method; orthogonal experiment; in vitro release; antitumor; druggability / 中草药

ABSTRACT

Objective: In view of druggability issue of limonin (LM), the liposomal preparation was developed. The liposomal formulation and preparation process were optimized, and its in vitro antitumor activity was investigated. Methods: In this study, LM was loaded in liposomes to increase its stability and solubility. Meanwhile, in vitro cytotoxicity of LM@Lip was evaluated. LM@Lip were prepared by thin-film dispersion method, and formulation selection and process optimization were operated by single factor and orthogonal experiment. Size distribution, PDI and zeta potential were measured by Malvern sizer, and the encapsulation efficiency and drug loading content were determined by HPLC. The dialysis method was used to investigate the release profile of LM@Lip. In vitro cytotoxicity against HepG2 and A549 cells were estimated by MTT method. Results: The optimized preparation conditions of liposomes were as follows drug/lipid ratio was 1150, cholesterol/lipid ratio was 19, the ultrasonic power was 120 W for 6 min (1 s interval). The average particle size, PDI and Zeta potential of optimized LM@Lip were (119.5 ± 6.2) nm, 0.318 ± 0.124, (-17.2 ± 1.3) mV, respectively, and the encapsulation efficiency and drug loading content were 87.9% and 0.57%. The final concentration of LM was 63.4 μg/mL. The release results showed 58.59% drug was released in 12 h. MTT results showed that the IC50 of LM@Lip on HepG2 and A549 cells was 20.16 and 15.39 μg/mL, respectively, and its in vitro antitumor was superior to that of LM. Conclusion: Liposomes can increase the stability and solubility of LM. LM@Lip showed slow-release profile and significant tumor inhibition superior to LM.