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ISSN: 2157-7609
Journal of Drug Metabolism & Toxicology
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Nanostructures for Drug Delivery

Vinit Kumar, Flavio Rizzolio and Giuseppe Toffoli*
Clinical Pharmacology, Department of Molecular Biology and Translational Research, National Cancer Institute, CRO Aviano, Italy
Corresponding Author : Giuseppe Toffoli
Clinical Pharmacology
Department of Molecular Biology
and Translational Research
National Cancer Institute CRO Aviano, Italy
E-mail: [email protected]
Received February 24, 2015, Accepted February 26, 2015, Published March 3, 2015
Citation: Kumar V, Rizzolio F, Toffoli G (2015) Nanostructures for Drug Delivery. J Drug Metab Toxicol 6:e125. doi:10.4172/2157-7609-1000e125
Copyright: © 2015, Kumar V et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Description
Nanotechnology deals mainly with the construction and manipulation of structures in the range of 1 to 100 nm and provides excellent means for the development of novel, clinically relevant diagnostic and therapeutic multifunctional systems. In the past decades, various examples of innovative nanostructures have been suggested as promising tools in drug delivery for cancer management, thus providing the opportunities for novel approaches to the clinical practice [1,2]. Advancement, in the development of nanostructures based Drug Delivery Systems (DDSs), made it possible to obtain modified release kinetics of drug through different routes and improving the efficacy of old drugs and delivering novel chemotherapeutic agents [2]. Thus, DDSs could improve the pharmaceutical efficacy of a particular drug and other related parameters like stability, release of the drugs from formulations, dissolution rate, absorption, distribution and metabolism [2,3]. With nanostructures based drug delivery, it is possible to achieve: (i) improved solubility of poorly water-soluble drugs; (ii) highly specific and targeted delivery of drugs; (iii) increased in vivo stability of drug; (iv) delivery of drug across the cellular membrane; and (v) delivery of a combination of chemotherapeutic agents to the proximity of the tumor [3].
In general, drug delivery is done by oral administration, intravenous and intraperitoneal injections [4]. However, in conventional therapy, relatively higher amount of drug is needed as the drug, after administration, tend to distribute non-specifically in the body producing in some cases severe side effects. Applications of nanostructures may increase the circulation time and maintain the required reactivity of the drug along with high selectivity which can ultimately decrease the amount of drug and thus their side effects.
Several DDS nanostructures have been constructed in the past. These include inorganic (nanoparticles mainly gold, magnetic and silica nanoparticles) and organic (carbon, polymers, vesicles and DNA) nanostructures. Nanostructures based formulations of drug viz, Doxil, Resovist, Ferides and Abraxane have already been achieved and are currently being used for clinical applications [2,3,5,6].
Almost five decades ago, liposomes (lipid vesicles) were reported and soon identified as a potential drug delivery carrier [2,3]. Some liposomes based anticancer drugs are already in the market while several others are under advance stages of clinical trials. Liposomes have been used to deliver doxorubicin, cisplatin, siRNA and other chemotherapeutic drugs [2,3,5]. In addition to passive targeting, liposomes can also be functionalized with ligands for active targeting and delivery. Liposomes based formulations have led to several clinical trials for delivery of various anti-cancer, anti-inflammatory, antibiotic and anti-fungal drugs [6].
Among metal based DDSs, gold nanoparticles (AuNPs) have been explored to a large extent owing to their simple synthesis with excellent control over their size, easy conjugation with drug molecules through strong Au-S bond [7]. AuNPs have been utilized for delivery of various drugs, proteins, DNA and RNA to the diseased cells [8]. The photothermal effect generated by AuNPs adds another advantage for killing cancerous cells. Although some groups reported that AuNPs have low toxicity, however it is still controversial [8,9].
Iron oxide nanoparticles are another class of metal nanostructures, which has been used extensively in biomedical research for drug delivery purposes [1,10]. The intrinsic magnetism of these particles can be used in targeted drug-delivery field, where the intravenously injected drug loaded NPs are guided magnetically to the targeted site and the release of drug molecules from their surface is achieved under an external magnetic field [10]. Several drug molecules, nucleic acids, and peptides have been delivered to cancerous part using iron oxide based DDSs.
Mesoporous silica nanostructures could be effectively utilized for the drug delivery applications [11]. Porous surface of these nanomaterials can entrap and contain drug as well as fluorophores, together with their higher colloidal stability, prove additional advantages for simultaneous tracking and thus can be effectively used for cancer theranostics.
Carbon based nanostructures viz., Carbon Nanotubes (CNT), graphene and carbon nanoparticles have been utilized for drug delivery applications [12-14]. However, in some cases CNT shows aggregation outside the cells making the drug delivery inefficient. Recently, discovered class of carbon based nanomaterials termed as Carbon Nanoparticles (CNPs) generated enormous interest for the construction of highly biocompatibility nanostructures for drug delivery [14,15]. We have also observed that CNP are non-toxic upto very high concentration (2 mg/mL) in vitro experiments (unpublished data). In fact, in an in vivo study, CNPs were administered to mouse intravenously and it has been demonstrated that these particles are largely nontoxic [16].
DNA nanotechnology is another complementary approach of significant potentials for drug delivery and could find a way to clinical applications in the near future. DNA being a genetic material should possess minimum toxicity while the robust complementary interactions of its base pairs make it an idea material for the construction of ‘smart’ functional biocompatible nanomaterials [17]. Various type of DNA nanostructure such as rectangular sheet, tetrahedron, icosahedrons, tube, and triangles have been successfully used in in vitro and in vivo applications [17,18]. However lower in vivo stability of DNA nanostructures is a limitation, which needs to be circumvented.
Overall, it could be concluded that by engineering the nanoparticle surface, passive or active targeting at pathological sites could preserve healthy tissues. However, active targeting is still in the initial stages of development and a thorough understanding of this phenomenon is required before their real clinical applications. Coating of nanostructures surface with PEG may further add biocompatibility by preventing the unspecific interaction of NPs with biological system through NPs surface. The size of the NPs is another important parameter influencing the pharmacokinetic and biodistribution of the injected NPs, which needed to be carefully analyzed. By applying nanotechnological approaches, it is possible to tune the drug release properties and thus the efficacy of any therapy. We believe that DDSs have immense potentials for minimizing toxicity and improved pharmacokinetic of drugs and will find their way in clinics in the near future for the treatment of various diseases. Nanomedicines, with great potential for minimizing toxicity, increasing bioavailability and/or improving pharmaco kinetic features of drugs, have seen enormous development on cancer therapy in the last dacades.
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