Zhou, Min, et al. Drug delivery 24.1 (2017): 1230-1242.
Challenge: Methods of cancer treatment that use single drugs have not been successful for the treatment of aggressive cancers such as metastatic melanoma. In addition to improving efficacy, another challenge is how to minimize systemic toxicity.
Solution: Formulation of a synergistic dual-drug delivery vehicle with AP and PTX co-loaded into solid lipid nanoparticles (AP/PTX-SLNs). This formulation used the biological activity and lipid solubility of AP to improve PTX delivery.
Preparation: AP/PTX-SLNs were prepared by modified ultrasonic method. Formulation ingredients were GMS, didodecyldimethylammonium bromide (DDAB), Pluronic F-68 and AP/PTX with a mass ratio of 2/1. Lipid/drug mixture were melted at 85°C and added into aqueous phase to form an emulsion. Then the emulsion was subject to sonication (50% amplitude, 25 min) and rapidly cooled. The nanoparticles were spherical and around 223 nm in diameter.
Key Findings:
· In vitro cell cytotoxicity experiments showed the best synergistic anticancer effect of the AP/PTX-SLNs formulation when the mass ratio was 2/1.
· In vivo tumor inhibition experiments proved that AP/PTX-SLNs significantly inhibited B16F10 tumor growth in mice, and eliminated tumor cells in the lungs, better than using either AP-SLNs or PTX-SLNs separately, through a synergistic effect reducing the Bcl-2/Bax ratio.
· Additionally, treatment with AP/PTX-SLNs did not result in significant side effects, suggesting that this co-delivery system with ascorbyl palmitate has strong clinical potential for cancer therapy.