DEVELOPMENT OF MIXED POLYMERSOMES FOR NANOENCAPSULATION OF PROTEINS

Nanostructure have proven effective for drug delivery, with polymeric nanostructures standing out in this regard. Polymersomes, for example, offer superior physicochemical stability and mechanical resilience compared to liposomes. Our group has been studying poloxamer 401 (PEO₅-PPO₆₂-PEO₅) polymersomes for the nanoencapsulation of proteins and a crucial step is the formulation drying. While lyophilization is the standard technique for drying nanostructures dispersed in aqueous media, it is not suitable for poloxamer-based polymersomes due to the critical temperature of these copolymers, which would result in disintegration of the polymeric vesicles. An alternative to address this problem is to create mixed-composition vesicles, thereby adjusting the thermal stability of the formed vesicles. Systems were prepared with different proportions of poloxamer 401 combined with PEO₄₅-PCL₄₄ and PEO₄₅-PLA₆₉, using the polymer film hydration method. The size and polydispersity index of the nanostructures were then determined by dynamic light scattering (DLS), and the detection and analysis of changes in the systems' heat capacity were performed using differential scanning calorimetry (DSC) and, additionally, through the cloud point test for determining the critical micellization temperature (CMT). Nanostructures with average sizes of 240 nm and an average polydispersity index of 0.2 were obtained. These characteristics were preserved within 4 weeks, even considering certain variation in the room temperature, thus demonstrating promising structural stability and thermal resistance. The thermal events observed by DSC were consistent with the known characteristics of the copolymers employed, and the CMT analyses showed a reduction in the upper critical temperature in formulations with both studied copolymers, particularly in formulations containing PEO₄₅-PCL₄₄, demonstrating that the combination of different copolymers may be effective in increasing the thermal stability poloxamer 401 nanostructures. These findings could improve our understanding of copolymer associations and contribute to developing more stable and effective formulations, which is crucial in pharmaceutical research and industry.