Encapsulation and release of antitumor drugs from polymeric micelles obtained by aqueous two-phase micellar systems and ionic liquids in the absence of organic solvents

Abstract

Cancer is one of the leading causes of death, surpassed only by cardiovascular diseases, and has an incidence of 11 million new cases each year worldwide. Therefore, nanotechnology-based drug delivery systems have received much attention for cancer treatment. The significant challenge of the most recent studies in this field is to create new types of smart nanocarriers capable of selectively responding to the specific cancer condition and rapidly releasing drug into target cells. In this sense, polymeric micelles (MPs) have attracted special attention as new nano-sized drug delivery systems to optimize the treatment and diagnosis of this disease. These nanocarriers exhibit advantages in vitro and in vivo, as well as excellent stability and solubility to hydrophobic drugs. One polymer category prominent for micelle self-assembly is the Pluronics, a unique class of synthetic triblock copolymers containing hydrophobic polypropylene oxide (PPO) and hydrophilic polyethylene oxide (PEO) arranged in a PEO-PPO-PEO due to its excellent biocompatibility and amphiphilic properties. A promising methodology to produce these micelles is the aqueous two-phase micellar system (ATPMS); the advantages are diverse, such as simple composition and relatively cheap process (water + amphiphilic copolymers/surfactant), low need for complex equipment, provide a weak environment for (bio)molecules and are ecologically sustainable (e.g., without the addition of solvents). On the other hand, ATPMS can offer challenges for phase separation (rich and poor in PMs), due, for example, to high temperatures for obtaining a biphasic system. These challenges can be overcome by using ionic liquids (ILs) as adjuvants in the process. Some of these compounds are able to decrease the phase separation temperature, improve the properties of PMs (less polydispersed systems), and influence the encapsulation rates of target (bio)molecules. In this context, this project proposes the development of an intelligent platform for the encapsulation of hydrophobic drugs (curcumin - CCM and paclitaxel - PTX), composed specifically of amphiphilic copolymers, PEO100-PPO65-PEO100 (i.e., Pluronic® F127) and PEG2000-PCL6000-PGA1000 (other diblock or triblock copolymers based on PMAA, PAA, PDMA, and/or PNIPAM will also be tested), based on ATPMS and ILs from the choline family (choline chloride - [Ch]Cl) and (choline hexanoate - [Ch][Hex]). The choice of these bioactives is due to their antitumor properties and the challenges in the encapsulation process, especially the low solubility of these molecules in an aqueous environment. (AU)