Challenges in development of nanoparticle-based therapeutics. AAPS J

Strategic Platforms, Abraxis BioScience, 11755 Wilshire Blvd., Suite 2300, Los Angeles, California 90025, USA.
The AAPS Journal (Impact Factor: 3.8). 03/2012; 14(2):282-95. DOI: 10.1208/s12248-012-9339-4
Source: PubMed

ABSTRACT 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.

12 Reads
  • Source
    • "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]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Neurodegeneration is the progressive loss of structure or function of neurons leading to neuronal death, usually associated with ageing. Some of the common neurodegenerative disorders include Alzheimer's disease, Parkinson's disease, Creutzfeldt-Jakob disease, and Huntington's disease. Due to recent advancements in high-throughput technologies in various disciplines such as genomics, epigenomics, metabolomics and proteomics, there has been a great demand for detection of specific macromolecules such as hormones, drug residues, miRNA, DNA, antibodies, peptides, proteins, pathogens and xenobiotics at nano-level concentrations for in-depth understanding of disease mechanisms as well as for the development of new therapeutic strategies. The present review focuses on the management of age-related neurodegenerative disorders using proteomics and nanotechnological approaches. In addition, this review also highlights the metabolism and disposition of nano-drugs and nano-enabled drug delivery in neurodegenerative disorders.
    Current Drug Metabolism 12/2014; · 2.98 Impact Factor
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: This study aimed to improve the targeting of superparamagnetic iron oxide nanoparticles (SPI-ONs) to the lung after intravenous administration. In order to achieve a higher pulmonary delivery, high-energy flexible magnets were optimized and externally applied to a specific region of mouse lung. SPIONs and magnets were first characterized, and a free-breathing magnetic resonance imaging (MRI) protocol was then optimized to allow noninvasive monitoring and for their sensitive detection to the target site in the lung, using an ultrashort time of echo radial MR pulse sequence. In addition, histological analysis using Perls' staining and iron quantification using inductive couple plasma-mass spectroscopy (ICP-MS) were performed to confirm MRI readouts. A flexible magnet with inverse multiple polarities was found to enhance the magnetic targeting of SPIONs to the lung. MRI readouts enabled successful detection of enhanced SPION migration to the lower right lobe, where the magnet was positioned. Attracted by the magnet, SPIONs were found to accumulate in the lung tissue within 2 h post-injection as seen in histological images and through ICP-MS, where a notable increase in iron concentrations were observed in the magnet group compared to control mice. In conclusion, the external application of an optimized high-energy magnet with multiple polarities over specific regions of the lung enhanced the magnetic targeting of SPIONs to the site of interest within the lung after intravenous injection.
    Journal of Nanoparticle Research 10/2014; 16(10-10):1-11. DOI:10.1007/s11051-014-2667-9 · 2.18 Impact Factor
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study is to characterize the in-vitro physicochemical and in-vivo pharmacokinetic properties of the scutellarin-loaded bovine serum albumin nanoparticles (STA-BSA-NPs). STA existed as amorphous form in the nanoparticles. Reconstituted STA-BSA-NPs had an average particle size of 283.4nm and a zeta potential of +17.95mV. The in-vitro sustained release profile was well fitted with Weibull distribution model. In comparison to STA solution, STA-BSA-NPs exhibited a significantly higher plasma concentration from 20min to 6h after intravenous administration to rats. In addition, significantly higher AUC0-inf (2.8-fold), prolonged elimination half-life (4.2-fold) and lower clearance (2.7-fold) were achieved.
    International Journal of Pharmaceutics 09/2014; 476(1-2). DOI:10.1016/j.ijpharm.2014.09.038 · 3.65 Impact Factor
Show more

Preview (3 Sources)

12 Reads
Available from