Preparation and Optimization Lipid Nanocapsules to Enhance the Antitumor Efficacy of Cisplatin in Hepatocellular Carcinoma HepG2 Cells
This work aimed to develop and optimize several lipid nanocapsule formulations (LNCs) to encapsulate cisplatin (CDDP) for treatment of hepatocellular carcinoma. By comparing the effect of oil/surfactant ratio, lecithin content, and oil/surfactant type on LNC characteristics, two LNCs were selected as optimal formulations: HS15-LNC (Solutol HS 15/MCT/lecithin, 54.5:42.5:3%, w/w) and EL-LNC (Cremophor EL/MCT/lecithin, 54.5:42.5:3%, w/w). Both LNCs could effectively encapsulate CDDP with the encapsulation efficiency of 73.48 and 78.84%. In vitro release study showed that both LNCs could sustain the release CDDP. Moreover, cellular uptake study showed that C6-labeled LNCs could be effectively internalized by HepG2 cells. Cellular cytotoxicity study revealed that both LNCs showed negligible cellular toxicity when their concentrations were below 313 μg/mL. Importantly, CDDP-loaded LNCs exhibited much stronger cell killing potency than free CDDP, with the IC50 values decreased from 17.93 to 3.53 and 5.16 μM after 72-h incubation. In addition, flow cytometric analysis showed that the percentage of apoptotic cells was significantly increased after treatment with LNCs. Therefore, the prepared LNC formulations exhibited promising anti-hepatocarcinoma effect, which could be beneficial to hepatocellular carcinoma therapy.
KEY WORDSlipid nanocapsule hepatocellular carcinoma cisplatin solutol HS 15 cremophor EL
This work was supported by the National Natural Science Foundation of China (Grant No. 81603186) and Educational Committee Foundation of Liaoning Province (Grant No. L2016026).
- 5.Shah M, Ullah N, Choi MH, Kim MO, Yoon SC. Amorphous amphiphilic P (3HV-co-4HB)-b-mPEG block copolymer synthesized from bacterial copolyester via melt transesterification: nanoparticle preparation, cisplatin-loading for cancer therapy and in vitro evaluation. Eur J Pharm Biopharm. 2012;80(3):518–27.CrossRefPubMedGoogle Scholar
- 8.Salimi F, Dilmaghani KA, Alizadeh E, Akbarzadeh A, Davaran S. Enhancing cisplatin delivery to hepatocellular carcinoma HepG2 cells using dual sensitive smart nanocomposite. Artif Cells Nanomed Biotechnol. 2017:1–10.Google Scholar
- 11.Zhang C, Nance EA, Mastorakos P, Chisholm J, Berry S, Eberhart C, et al. Convection enhanced delivery of cisplatin-loaded brain penetrating nanoparticles cures malignant glioma in rats. J Control Release. 2017;263:112–9. https://doi.org/10.1016/j.jconrel.2017.03.007.CrossRefPubMedPubMedCentralGoogle Scholar
- 30.Matsaridou I, Barmpalexis P, Salis A, Nikolakakis I. The influence of surfactant HLB and oil/surfactant ratio on the formation and properties of self-emulsifying pellets and microemulsion reconstitution. AAPS PharmSciTech. 2012;13(4):1319–30. https://doi.org/10.1208/s12249-012-9855-7.CrossRefPubMedPubMedCentralGoogle Scholar
- 32.Roy U, Ding H, Pilakka-Kanthikeel S, Raymond AD, Atluri V, Yndart A, et al. Preparation and characterization of anti-HIV nanodrug targeted to microfold cell of gut-associated lymphoid tissue. Int J Nanomedicine. 2015;10:5819–35. https://doi.org/10.2147/IJN.S68348.CrossRefPubMedPubMedCentralGoogle Scholar
- 34.Hatahet T, Morille M, Shamseddin A, Aubert-Pouëssel A, Devoisselle JM, Bégu S. Dermal quercetin lipid nanocapsules: influence of the formulation on antioxidant activity and cellular protection against hydrogen peroxide. Int J Pharm. 2017;518(1):167–76. https://doi.org/10.1016/j.ijpharm.2016.12.043.CrossRefPubMedGoogle Scholar
- 35.Torge A, Wagner S, Chaves PS, Oliveira EG, Guterres SS, Pohlmann AR, et al. Ciprofloxacin-loaded lipid-core nanocapsules as mucus penetrating drug delivery system intended for the treatment of bacterial infections in cystic fibrosis. Int J Pharm. 2017;527(1):92–102. https://doi.org/10.1016/j.ijpharm.2017.05.013.CrossRefPubMedGoogle Scholar
- 36.de Andrade DF, Zuglianello C, Pohlmann AR, Guterres SS, Beck RC. Assessing the in vitro drug release from lipid-core nanocapsules: a new strategy combining dialysis sac and a continuous-flow system. AAPS PharmSciTech. 2015;16(6):1409–17. https://doi.org/10.1208/s12249-015-0330-0.CrossRefPubMedPubMedCentralGoogle Scholar
- 38.Lv X, Liu T, Ma H, Tian Y, Li L, Li Z, et al. Preparation of essential oil-based microemulsions for improving the solubility, pH stability, photostability, and skin permeation of quercetin. AAPS PharmSciTech. 2017:1–8.Google Scholar
- 42.Lollo G, Vincent M, Ullio-Gamboa G, Lemaire L, Franconi F, Couez D, et al. Development of multifunctional lipid nanocapsules for the co-delivery of paclitaxel and CpG-ODN in the treatment of glioblastoma. Int J Pharm. 2015;495(2):972–80. https://doi.org/10.1016/j.ijpharm.2015.09.062.CrossRefPubMedGoogle Scholar