Purification processes of polymeric nanoparticles: How to improve their clinical translation?

Polymeric nanoparticles, as revolutionary nanomedicines, have offered a new class of diagnostic and therapeutic solutions for a multitude of diseases. With its immense potential, the world witnesses the new age of nanotechnology after the COVID-19 vaccines were developed based on nanotechnology. Even though there are countless benchtop research studies in the nanotechnology world, their integration into commercially available technologies is still restricted. The post-pandemic world demands a surge of research in the domain, which leaves us with the fundamental question: why is the clinical translation of therapeutic nanoparticles so restricted? Complications in nanomedicine purification, among other things, are to blame for the lack of transference. Polymeric nanoparticles, owing to their ease of manufacture, biocompatibility, and enhanced efficiency, are one of the more explored domains in organic-based nanomedicines. Purification of nanoparticles can be challenging and necessitates tailoring the available methods in accordance with the polymeric nanoparticle and impurities involved. Though a number of techniques have been described, there are no available guidelines that help in selecting the method to better suit our requirements. We encountered this difficulty while compiling articles for this review and looking for methods to purify polymeric nanoparticles. The currently accessible bibliography for purification techniques only provides approaches for a specific type of nanomaterial or sometimes even procedures for bulk materials, that are not fully relevant to nanoparticles. In our research, we tried to summarize the available purification techniques using the approach of A.F. Armington. We divided the purification systems into two major classes, namely: phase separation-based techniques (based on the physical differences between the phases) and matter exchange-based techniques (centered on physicochemical induced transfer of materials and compounds). The phase separation methods are based on either using nanoparticle size differences to retain them on a physical barrier (filtration techniques) or using their densities to segregate them (centrifugation techniques). The matter exchange separation methods rely on either transferring the molecules or impurities across a barrier using simple physicochemical phenomena, like the concentration gradients (dialysis method) or partition coefficients (extraction technique). After describing the methods in detail, we highlight their advantages and limitations, mainly focusing on preformed polymer-based nanoparticles. Tailoring a purification strategy takes into account the nanoparticle structure and its integrity, the method selected should be suited for preserving the integrity of the particles, in addition to conforming to the economical, material and productivity considerations. In the meantime, we advocate the use of a harmonized international regulatory framework to define the adequate physicochemical and biological characterization of nanomedicines. An appropriate purification strategy serves as the backbone to achieving desired characteristics, in addition to reducing variability. As a result, the present review aspires to serve as a comprehensive guide for researchers, who are new to the domain, as well as a synopsis of purification strategies and analytical characterization methods used in preclinical studies.