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Toxicological Profile of Therapeutic Nanodelivery Systems

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Several of the newly developed drug molecules show potent biological activity, but exhibit poor pharmacokinetic properties that may hinder their effective delivery to the intended site of action. In order to improve their pharmacological effect, these molecules can be associated with drug carriers in order to overcome these inherent difficulties. An ideal drug delivery agent requires therefore biocompatibility, improved solubility of a loaded drug or peptide, releasing of the payload at the absorption site and, at the same time, leaving undisturbed cell structure and function, and maintaining the physiological milieu. By taking advantage of the valuable properties of nanoscale delivery systems, such as increased surface area, improved solubility of hydrophobic drugs, possibility to encapsulate and protect drugs from degradation and reduced immunogenic potential and toxicological effect, new therapeutic options can be brought forth and improve the clinical arsenal for numerous diseases. The use of nanodelivery systems can even promote the re-investigation of pharmacokinetically less favourable, but biologically more active compounds. Although very promising, these systems may also encompass inherent toxicological issues, mainly due to their size and shape, physical interaction with cellular membranes and organelles, immunological reactions, long- or short-term tissue accumulation, and degradation products. Pharmaceutical nanodelivery systems, such as liposomes, polymeric nanoparticles, dendrimers and mesoporous silica and silicon based nanoparticles have shown great potential in preclinical applications and several of these nanosystems are even undergoing clinical trials. They have been found to combine drug delivery properties with an acceptable toxicological profile, which has made them prime candidates for several drug delivery approaches. This review aims to provide and correlate the toxicological studies with the drug delivery properties of the abovementioned nanodelivery systems in particular concerning uptake and accumulation as well as the critical aspects in each system regarding their optimal performance, while pointing out to the most relevant references.
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Keywords: Accumulation; Nanodelivery Systems; Potent; RNOS; ROS; SEM; cytotoxicity; dendrimers; immunoassays; liposomes; mesoporous; morphology; nanoparticles; oxidative stress; silica; silicon; toxicity

Document Type: Research Article

Publication date: October 1, 2012

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  • Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism and disposition. The journal serves as an international forum for the publication of timely reviews in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments. The journal covers the following areas:

    In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites and adducts.
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