Development of Nanocochleates Containing Erlotinib HCl and Dexketoprofen Trometamol and Evaluation of In Vitro Characteristic Properties

[摘要] Objectives: Erlotinib HCI is a tyrosine kinase receptor inhibitor and an anticancer agent that was first approved by the FDA in 2004 for treatment of non-small-cell lung cancer and pancreatic cancer. Dexketoprofen trometamol is a NSAID, but recent studies showed that dexketoprofen trometamol also had an effect in carcinoma due to its inhibitor effects on prostaglandins. The combination of dexketoprofen and anti-cancer agents reduces pain caused by cancer by diminishing the tumors pressure, which causes necrosis; it also lowers the poor prognosis of cancer. Combination therapy will make life easier for patients, considering drug administration and dosing. Nanocochleates are new drug delivery systems that have not been examined as much as liposomes, but they have more advantages than liposomes. Materials and Methods: In this study, erlotinib HCl and dexketoprofen trometamol were loaded into nanocochleates with various formulations and particle sizes/distributions, polydispersity indexes, and zeta potential analyses were performed. Transmission electron microscopy imaging was performed with the obtained optimal formulation and drug-release studies using Franz diffusion cells were conducted. Results: As a result, drug carrier systems with a particle size of 196.42-312.33 nm and zeta potential greater than 15 mV were produced. The highest encapsulation efficiency for the main active ingredient, erlotinib HCl, was obtained in the KOH-1B formulation with 86.22±1.45%. Conclusion: This study showed that the drugs were successfully loaded into the nanocochleates and the nanocochleates actively released the drugs.

[关键词] Nanocochleate;erlotinib HCl;Franz diffusion cell