Desai, N. Challenges in development of nanoparticle-based therapeutics. AAPS J 14: 282-295

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The AAPS Journal (Impact Factor: 3.8). 03/2012; 14(2):282-95. DOI: 10.1208/s12248-012-9339-4
Source: PubMed


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.

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    • "Due to their large surface area, nanodrugs can further enhance the solubility of poorly soluble drugs and also increase their half-lives by controlling the speed of degradation in vivo, thus augmenting drugs' efficacy and lowering their side effects [184] [185] [186] [187]. After entering the body, drug and NPs get separated under a constant speed thus creating a time lapse before they reach their targets [188]. Nano-drugs have been reported to reach into specific body parts mainly by infiltration, leaching and proliferation (dissolution) [189]. "
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    • "While, with passive targeting, the accumulation of the nanoprobes within the diseased area (i.e., inflammatory or tumor sites) is accomplished by the enhanced permeability and retention (EPR) effect (Maeda et al. 2000) generally not specific to a unique target site, active targeting requires the conjugation of the nanocarrier system to a tissue or cell-specific ligand (e.g., antibody). However , significant challenges—related to the selection of appropriate target, methods to incorporate correct targeting moieties, and strategies to avoid the rapid clearance of the delivery vehicles from the body—still exist for effective active targeting (Desai 2012; Moghimi et al. 2005). With their unique superparamagnetic effect, SPION-based nanocarriers have the potential to be attracted by a magnet, and therefore, their specific targeting can be improved by actively directing the particles to the site of action by placing an external magnet (Barakat 2009). "
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    • "Particle size and its distribution are the most widely accepted defining characteristics of nanoparticle-based medicines since particle size can significantly influence the pharmacokinetics, biodistribution, and safety of nanoparticulate drugs (Desai, 2012). "
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