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.

Stimuli-Responsive Polymeric Nanocarriers for Drug Delivery, Imaging, and Theragnosis.

In the past few decades, polymeric nanocarriers have been recognized as promising tools and have gained attention from researchers for their potential to efficiently deliver bioactive compounds, including drugs, proteins, genes, nucleic acids, etc., in pharmaceutical and biomedical applications. Remarkably, these polymeric nanocarriers could be further modified as stimuli-responsive systems based on the mechanism of triggered release, i.e., response to a specific stimulus, either endogenous (pH, enzymes, temperature, redox values, hypoxia, glucose levels) or exogenous (light, magnetism, ultrasound, electrical pulses) for the effective biodistribution and controlled release of drugs or genes at specific sites. Various nanoparticles (NPs) have been functionalized and used as templates for imaging systems in the form of metallic NPs, dendrimers, polymeric NPs, quantum dots, and liposomes. The use of polymeric nanocarriers for imaging and to deliver active compounds has attracted considerable interest in various cancer therapy fields. So-called smart nanopolymer systems are built to respond to certain stimuli such as temperature, pH, light intensity and wavelength, and electrical, magnetic and ultrasonic fields. Many imaging techniques have been explored including optical imaging, magnetic resonance imaging (MRI), nuclear imaging, ultrasound, photoacoustic imaging (PAI), single photon emission computed tomography (SPECT), and positron emission tomography (PET). This review reports on the most recent developments in imaging methods by analyzing examples of smart nanopolymers that can be imaged using one or more imaging techniques. Unique features, including nontoxicity, water solubility, biocompatibility, and the presence of multiple functional groups, designate polymeric nanocues as attractive nanomedicine candidates. In this context, we summarize various classes of multifunctional, polymeric, nano-sized formulations such as liposomes, micelles, nanogels, and dendrimers.

Molecular insights and novel approaches for targeting tumor metastasis.

In recent years, due to the effective drug delivery and preciseness of tumor sites or microenvironment, the targeted drug delivery approaches have gained ample attention for tumor metastasis therapy. The conventional treatment approaches for metastasis therapy have reported with immense adverse effects because they exhibited maximum probability of killing the carcinogenic cells along with healthy cells. The tumor vasculature, comprising of vasculogenic impressions and angiogenesis, greatly depends upon the growth and metastasis in the tumors. Therefore, various nanocarriers-based delivery approaches for targeting to tumor vasculature have been attempted as efficient and potential approaches for the treatment of tumor metastasis and the associated lesions. Furthermore, the targeted drug delivery approaches have found to be most apt way to overcome from all the limitations and adverse effects associated with the conventional therapies. In this review, various approaches for efficient targeting of pharmacologically active chemotherapeutics against tumor metastasis with the cohesive objectives of prognosis, tracking and therapy are summarized.