Challenges in Development of Nanoparticle-Based Therapeutics

By N. Desai. AAPS Journal, 2012

981 citations recorded by the source corpus.

In recent years, nanotechnology has been increasingly applied to the area of drug development. Nanoparticle-based therapeutics can confer the ability to overcome biological barriers, effectively deliver hydrophobic drugs and biologics, and preferentially target sites of disease. However, despite these potential advantages, only a relatively small number of nanoparticle-based medicines have been approved for clinical use, with numerous challenges and hurdles at different stages of development. The complexity of nanoparticles as multi-component three dimensional constructs requires careful design and engineering, detailed orthogonal analysis methods, and reproducible scale-up and manufacturing process to achieve a consistent product with the intended physicochemical characteristics, biological behaviors, and pharmacological profiles. The safety and efficacy of nanomedicines can be influenced by minor variations in multiple parameters and need to be carefully examined in preclinical and clinical studies, particularly in context of the biodistribution, targeting to intended sites, and potential immune toxicities. Overall, nanomedicines may present additional development and regulatory considerations compared with conventional medicines, and while there is generally a lack of regulatory standards in the examination of nanoparticle-based medicines as a unique category of therapeutic agents, efforts are being made in this direction. This review summarizes challenges likely to be encountered during the development and approval of nanoparticle-based therapeutics, and discusses potential strategies for drug developers and regulatory agencies to accelerate the growth of this important field.

Subfields: Biomaterials, Computational Theory and Mathematics, Materials Chemistry

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Citations in the corpus

Nanoparticle-liver interactions: Cellular uptake and hepatobiliary elimination. (2016, background): “Nanoparticles undergo intracellular degradation inside MPS cells when phagocytosed, and if they are not decomposed by these intracellular processes, they will remain within the cell and be sequestered in the spleen and liver for more than six months [87,104,120,121].”
Nanoparticle-based drug delivery systems: a commercial and regulatory outlook as the field matures (2017, background): “The literature on nano-manufacturing processes and industrial characterization methodologies is limited [14,22,47,49].”
Nanoemulsion: Concepts, development and applications in drug delivery (2017, background): “Nanoemulsions are subject to opsonisation and phagocytosis by circulatory macrophages and may be trafficked to perforated reservoirs such as spleen or liver, where immune cells usually reside [62,100].”
Polymeric nanoparticles: Promising platform for drug delivery. (2017, background): “For FDA pre-clinical and clinical validation review, the appropriate identification of such nanoparticle, including structure, synthesis methodology, quality and purity and many other basic categorization and characterization information must be included for submission as part of Investigational New”
Bovine milk-derived exosomes for drug delivery (2015, background): “The development of ideal nanoparticles with attributes such as long circulation time, evasion of the host immune system, and ability to target specific cells, minimum off site toxicity, and ability to carry versatile therapeutics remains elusive [7, 8].”
Nanoparticles in the clinic (2016, background): “, study design and approval challenges).(11,12) This review focuses on the clinical translation of intravenously administered nanoparticles, with additional emphasis on the challenges faced by nanoparticles from a clinical and translational point of view.”