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

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


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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    • "Over recent decades, the field of nanoparticle-based medicine has received particular attention as it holds the promise of revolutionizing medical treatment with more potent, less toxic, and smarter therapeutics that can target sites of disease. Therapeutic nanoparticles can confer the ability to overcome biological barriers and effectively deliver hydrophobic, poorly water-soluble drugs, and biologics (Desai, 2012). Currently, natural and synthetic polymers are typically used as drug delivery vectors. "
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    ABSTRACT: Albumin nanoparticles are one of the most important drug carriers for the delivery of therapeutic drugs, especially for the treatment of malignancies. This potential is due to their high binding capacity for both hydrophobic and hydrophilic drugs and the possibility of surface modification. Accumulation of albumin-bound drugs in the tumor interstitium occurs by the enhanced permeability and retention effect, which is also facilitated by the 60-kDa glycoprotein transcytosis pathway and binding to secreted protein, acidic and rich in cysteine located in the tumor extracellular matrix. In addition, specific ligands such as monoclonal antibodies, folic acid, transferrin, and peptides can be conjugated to the surface of albumin nanoparticles to actively target the drug to its site of action. The albumin-bound paclitaxel, Abraxane®, is one of the several therapeutic nanocarriers that have been approved for clinical use. By the development of Abraxane® that demonstrates a higher response rate and improved tolerability and therapeutic efficiency in comparison with solvent-based formulation, and with consideration of its commercial success, albumin is attracting the interest of many biotechnological and pharmaceutical companies. This chapter explores the current targeted and nontargeted albumin-based nanoparticles that are in various stages of development for the delivery of therapeutic agents in order to enhance the efficacy of cancer treatment. © 2015 Elsevier Inc. All rights reserved.
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    • "In 2015, Sinha et al. have successfully evaluated the contraceptive performance of a highly biocompatible oil/water nanoemulsion of papaya seed oil[11]. In addition, nanoemulsions are reported to be best suited for topical delivery of drugs as it enhances the pharmacokinetic (PK) properties of drugs than the oral route of drug delivery[12,13]. Therefore, considering very poor bioavailability of Nestorone upon oral ingestion, it is not advisable to be taken orally. "

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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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    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.
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