Antitumor Efficacy of a Complex Liposomal Formulation for Co-Delivery of Paclitaxel Palmitate and Adriamycin

Abstract

The combination of paclitaxel (PTX) and adriamycin (DOX) is an important option for the treatment of breast cancer in the clinic, but the traditional combination suffers from the defects of poor therapeutic efficacy with obvious toxic side effects. In our previous study, we synthesized paclitaxel palmitate (PTX-PA), which significantly improved the short half-life defect of PTX and is a good alternative to PTX. Therefore, this study utilized an ethanol injection method to coencapsulate PTX-PA and DOX, resulting in the preparation of a composite liposome (PTX-PA-DOX-L). A series of in vitro and in vivo experiments were conducted to evaluate its stability, safety, and therapeutic efficacy in the 4T1 breast cancer model. The results showed that the particle size of PTX-PA-DOX-L was stable at 108.2 ± 0.9 nm ( x ′ s ± s, n = 3), the polydispersity index (PDI) was 0.10 ± 0.01 ( x ′ s ± s, n = 3), the zeta potential was −23 ± 1 mV ( x ′ s ± s, n = 3), and the encapsulation efficiency (EE) of PTX-PA and DOX were 98.57 ± 0.81% and 98.44 ± 0.61%, respectively. It exhibits a favorable sustained release profile. In addition, the liposomes were made into lyophilized powder injections by combining freeze-drying technology, which could maintain the stability for up to 6 months even when stored at room temperature, and it was confirmed that PTX-PA-DOX-L complied with the requirements for injection, significantly prolonged the half-life of the drug, and last, because of its good tumor targeting ability, which not only enhanced the antitumor efficacy, but also effectively reduced the systemic toxicity. In conclusion, this study developed a compound liposome formulation with good safety and significant antitumor effect for the defects of PTX and DOX combination, which provides a strategy of coadministration for the clinical treatment of breast cancer.

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