Preparation of pH-responsive solanesol-based poly (glutamic acid) micellar carrier for doxorubicin delivery

This study focuses on the development of a new preparation method of solanesol derivatives for their effective use as drug carriers. The current preparation methods for solanesol derivatives generally suffer from poor accessibility and low yields of the target products, which affect the further development of their products. To address this issue, a solanesol-based poly (glutamic acid) (Sol-PEG-PGA) was first designed on the basis of the click reaction between alkynyl-functionalized solanesol and amino-polyethylene glycol (PEG)-azide, followed by a coupling reaction with poly (glutamic acid). The introduced polyethylene glycol and poly (glutamic acid) conferred amphipathic properties on solanesol. Sol-PEG-PGA possessed a suitable lipid-water partition coefficient of 1.01 and water contact angle of 55° and could self-assemble into spherical micelles with an average diameter of 74.0 ± 3.5 nm to load doxorubicin (DOX) via hydrophobic interaction, with a loading capacity of 27.7 ± 1.2%. Besides, Sol-PEG-PGA micelle exhibited excellent stability before and after loading DOX under the dilution of 1000 times and could be stored stably at room temperature for 15 days. The DOX loaded into Sol-PEG-PGA could be released by acid induction, with a cumulative release of 84.8 ± 2.5% at pH 5.0. Furthermore, in vitro cytotoxicity assay, the normal cells NIH/3T3 treated with Sol-PEG-PGA maintained relatively high viability of 95.0% compared to that of free DOX at 320 µg/mL, verifying its good biocompatibility. The DOX loaded into Sol-PEG-PGA possessed a high-efficiency anticancer activity compared to free DOX, with an inhibition rate of 99.2 ± 1.6% against tumor cells 4T1, suggesting the potentials of Sol-PEG-PGA for drug delivery applications. This new preparation method is expected to provide a new strategy for constructing various functional carriers from solanesol derivatives. • A novel pH-responsive solanesol-based poly (glutamic acid) micellar carrier was synthesized based on click reaction and coupling reaction. • Solanesol-based poly (glutamic acid) (Sol-PEG-PGA) micellar carrier achieved enhanced DOX-loading capacity of 27.7 ±1.2%. • DOX loaded into Sol-PEG-PGA micelle can exert more effective inhibition on tumor 4T1 cells. • A new strategy is provided for the construction of various functional solanesol derivatives.