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      Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems

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          Abstract

          Lipid-based drug delivery systems, or lipidic carriers, are being extensively employed to enhance the bioavailability of poorly-soluble drugs. They have the ability to incorporate both lipophilic and hydrophilic molecules and protecting them against degradation in vitro and in vivo. There is a number of physical attributes of lipid-based nanocarriers that determine their safety, stability, efficacy, as well as their in vitro and in vivo behaviour. These include average particle size/diameter and the polydispersity index (PDI), which is an indication of their quality with respect to the size distribution. The suitability of nanocarrier formulations for a particular route of drug administration depends on their average diameter, PDI and size stability, among other parameters. Controlling and validating these parameters are of key importance for the effective clinical applications of nanocarrier formulations. This review highlights the significance of size and PDI in the successful design, formulation and development of nanosystems for pharmaceutical, nutraceutical and other applications. Liposomes, nanoliposomes, vesicular phospholipid gels, solid lipid nanoparticles, transfersomes and tocosomes are presented as frequently-used lipidic drug carriers. The advantages and limitations of a range of available analytical techniques used to characterize lipidic nanocarrier formulations are also covered.

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          Most cited references92

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          Transdermal drug delivery.

          Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, noncavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin's barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase its impact on medicine.
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            Critical Evaluation of Nanoparticle Tracking Analysis (NTA) by NanoSight for the Measurement of Nanoparticles and Protein Aggregates

            Purpose To evaluate the nanoparticle tracking analysis (NTA) technique, compare it with dynamic light scattering (DLS) and test its performance in characterizing drug delivery nanoparticles and protein aggregates. Methods Standard polystyrene beads of sizes ranging from 60 to 1,000 nm and physical mixtures thereof were analyzed with NTA and DLS. The influence of different ratios of particle populations was tested. Drug delivery nanoparticles and protein aggregates were analyzed by NTA and DLS. Live monitoring of heat-induced protein aggregation was performed with NTA. Results NTA was shown to accurately analyze the size distribution of monodisperse and polydisperse samples. Sample visualization and individual particle tracking are features that enable a thorough size distribution analysis. The presence of small amounts of large (1,000 nm) particles generally does not compromise the accuracy of NTA measurements, and a broad range of population ratios can easily be detected and accurately sized. NTA proved to be suitable to characterize drug delivery nanoparticles and protein aggregates, complementing DLS. Live monitoring of heat-induced protein aggregation provides information about aggregation kinetics and size of submicron aggregates. Conclusion NTA is a powerful characterization technique that complements DLS and is particularly valuable for analyzing polydisperse nanosized particles and protein aggregates.
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              Cellular uptake, intracellular trafficking, and cytotoxicity of nanomaterials.

              The interactions of nanoparticles with the soft surfaces of biological systems like cells play key roles in executing their biomedical functions and in toxicity. The discovery or design of new biomedical functions, or the prediction of the toxicological consequences of nanoparticles in vivo, first require knowledge of the interplay processes of the nanoparticles with the target cells. This article focusses on the cellular uptake, location and translocation, and any biological consequences, such as cytotoxicity, of the most widely studied and used nanoparticles, such as carbon-based nanoparticles, metallic nanoparticles, and quantum dots. The relevance of the size and shape, composition, charge, and surface chemistry of the nanoparticles in cells is considered. The intracellular uptake pathways of the nanoparticles and the cellular responses, with potential signaling pathways activated by nanoparticle interactions, are also discussed. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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                Author and article information

                Journal
                Pharmaceutics
                Pharmaceutics
                pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                18 May 2018
                June 2018
                : 10
                : 2
                : 57
                Affiliations
                Australasian Nanoscience and Nanotechnology Initiative, 8054 Monash University LPO, Clayton, Victoria 3168, Australia; danagenepk@ 123456gmail.com (M.Da.); m_dehghan.kh@ 123456yahoo.com (M.De.); s.ataei@ 123456umsha.ac.ir (S.A.); Hasanzadeh.fatemeh1662@ 123456gmail.com (F.H.D.); r.javanmard@ 123456gmail.com (R.J.); info@ 123456anni.com.au (A.D.); dr.sepideh.khorasani@ 123456gmail.com (S.K.)
                Author notes
                [* ]Correspondence: dr.m.r.mozafari@ 123456gmail.com ; Tel.: +61-42433-9961
                Author information
                https://orcid.org/0000-0002-4118-1544
                Article
                pharmaceutics-10-00057
                10.3390/pharmaceutics10020057
                6027495
                29783687
                050a1a44-f6c1-4483-90b6-e2f1a129342a
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 14 April 2018
                : 17 May 2018
                Categories
                Review

                drug delivery,encapsulation,lipidic nanovesicles,nanocarriers,particle size,toxicity

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