A Critical Analysis of Polymersome Therapeutics: From Laboratory to Large-Scale Production

Abstract

Introduction Polymersomes as a synthetic evolution of liposomes Vesicular compartments are responsible for an organized separation within the cell and were crucial to the generation of life and the evolution. Vesicles produced by self-assembling of amphiphilic lipids arose as a promising technology for mimicking bio-available compartments, as well as its advantages related to chemical gradients, energy storage, stimuli responsiveness, and others. After the first description of liposomes in the mid-60s, they became present in many biotechnological applications. In 2005, the FDA approved the first liposome-based drug delivery carrier, Doxil® (doxorubicin HCl liposome injection, Janssen Products, LP). Over the years, the use of an inert polymer as an adjuvant in liposome constitution was vital, and polyethylene glycol (PEG) provided improvements in biodistribution with minimal side effects [1], both of which relevant characteristics for drug delivery [2,3]. Therefore, polymersomes, comprised of amphiphilic block copolymers (BCPs), emerged as a promising alternative to liposomes [4,5]. Both present analog lamellar membrane structure. Polymer vesicles display modifications in structural features of self-assembled vesicles, and therefore show enhanced stability compared with liposomes. Moreover, the high diversity and versatility of synthetic polymers enables the modulation of physicochemical properties related to membrane thickness, composition, permeability, stimuli-responsiveness, particle morphology and size, according to the desired application [6-12]. He high stability and robustness of these structures, however, could be addressed as a disadvantage towards becoming a functional drug delivery system. For this reason, stimuli-responsive polymersomes appear as an alternative to deliver the inside content upon demand, using, for instance pH, temperature, and osmotic differences, or ultrasound as an exogenous stimulus [13,14]. Moreover, biocompatible polymersomes were already tested in vivo as drug carriers and demonstrated its great potential for therapeutic applications [15,16]. Figure 1: TEM images of PEG-b-PLA polymersomes prepared by film hydration followed by sonication without (a) and with (b) drug content.