Polymersomes development aiming at the co-encapsulation of drugs for application in cancer therapy

Nanostructures for encapsulation of antitumoral drugs have been widely studied in recent years due to their important advantages, e.g., controlled and sustained release, fewer adverse effects, increased drug solubility, and lower chances of generating resistance to their administration (MDR effect), among others. In this context, this work intends to describe the main nanostructures used as drug delivery systems (DDS) for the encapsulation of antitumoral drugs (doxorubicin - DOX and curcumin - CUR). Furthermore, we investigated the essential parameters in the production of poly(ethylene glycol)-b-poly(?-caprolactone) (PEG-PCL) based polymersomes (Ps) for the co-encapsulation of DOX and vemurafenib (VEM). Three PEG-PCL copolymers were studied: PEG45PCL44, PEG114PCL98, and PEG114PCL114. We evaluated the effects of the parameters: agitation speed and time, hydration volume, and ultrasound time through two factorial designs (23), in the response variables: average particle size (DH) and polydispersity index (PDI), aiming to reach a better (lower) DH and PDI results. The DH and PDI values ranged from 210 to 245 nm and 0.117 to 0.148, respectively. Additionally, the co-encapsulation of DOX and VEM resulted in drug loading of 12 to 18% and 16 to 26% and encapsulation efficiency of 35 to 39% and 43 to 55%, respectively. The nanoformulation remained stable at 4, 25, and 37°C, and drug release was faster in those Ps composed of the smallest PEG-PCL blocks (i.e., PEG45PCL44 > PEG114PCL98 > PEG114PCL114), as well as in more acidic environments (i.e., pH 5.0 at 37°C, found in tumor environment). According to the results obtained, the best condition for obtaining Ps based on PEG-PCL was to use 1050 rpm stirring speed for 42 h, hydration volume of 15 mL (0.05% m/v), and ultrasound for 35 min at 25°C. Therefore, we believe that the developed nanoformulations can be a promising approach with potential synergistic effect, lower dosage, and lower risk of MDR in cancer therapy (AU)