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      New Advances in General Biomedical Applications of PAMAM Dendrimers

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          Abstract

          Dendrimers are nanoscopic compounds, which are monodispersed, and they are generally considered as homogeneous. PAMAM (polyamidoamine) was introduced in 1985, by Donald A. Tomalia, as a new class of polymers, named ‘starburst polymers’. This important contribution of Professor Tomalia opened a new research field involving nanotechnological approaches. From then on, many groups have been using PAMAM for diverse applications in many areas, including biomedical applications. The possibility of either linking drugs and bioactive compounds, or entrapping them into the dendrimer frame can improve many relevant biological properties, such as bioavailability, solubility, and selectivity. Directing groups to reach selective delivery in a specific organ is one of the advanced applications of PAMAM. In this review, structural and safety aspects of PAMAM and its derivatives are discussed, and some relevant applications are briefly presented. Emphasis has been given to gene delivery and targeting drugs, as advanced delivery systems using PAMAM and an incentive for its use on neglected diseases are briefly mentioned.

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          Most cited references137

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          In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis.

          A comparative in vitro cytotoxicity study with different water-soluble, cationic macromolecules which have been described as gene delivery systems was performed. Cytotoxicity in L929 mouse fibroblasts was monitored using the MTT assay and the release of the cytosolic enzyme lactate dehydrogenase (LDH). Microscopic observations were carried out as indicators for cell viability. Furthermore, hemolysis of erythrocytes was quantified spectrophotometrically. To determine the nature of cell death induced by the polycations, the nuclear morphology after DAPI staining and the inhibition of the toxic effects by the caspase inhibitor zVAD.fmk were investigated. All assays yielded comparable results and allowed the following ranking of the polymers with regard to cytotoxicity: Poly(ethylenimine)=poly(L-lysine)>poly(diallyl-dimethyl-ammonium chloride)>diethylaminoethyl-dextran>poly(vinyl pyridinium bromide)>Starburst dendrimer>cationized albumin>native albumin. The magnitude of the cytotoxic effects of all polymers were found to be time- and concentration dependent. The molecular weight as well as the cationic charge density of the polycations were confirmed as key parameters for the interaction with the cell membranes and consequently, the cell damage. Evaluating the nature of cell death induced by poly(ethylenimine), we did not detect any indication for apoptosis suggesting that the polymer induced a necrotic cell reaction. Cell nuclei retained their size, chromatin was homogenously distributed and cell membranes lost their integrity very rapidly at an early stage. Furthermore, the broad spectrum caspase inhibitor zVAD.fmk did not inhibit poly(ethylenimine)-induced cell damage. Insights into the structure-toxicity relationship are necessary to optimize the cytotoxicity and biocompatibility of non-viral gene delivery systems.
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            Starburst Dendrimers: Molecular-Level Control of Size, Shape, Surface Chemistry, Topology, and Flexibility from Atoms to Macroscopic Matter

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              Preparation of polymers with controlled molecular architecture. A new convergent approach to dendritic macromolecules

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                Author and article information

                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                02 November 2018
                November 2018
                : 23
                : 11
                : 2849
                Affiliations
                Laboratory of Design and Synthesis of Chemotherapeutics Potentially Active in Neglected Diseases (LAPEN), Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of São Paulo—USP, 580–Building 13, São Paulo SP 05508-900, Brazil; renan.arajo@ 123456usp.br (R.V.d.A.); soraya.ssantos@ 123456yahoo.com.br (S.d.S.S.); elizabeth.igne@ 123456gmail.com (E.I.F.)
                Author notes
                [* ]Correspondence: jeanineg@ 123456usp.br ; Tel.: +55-11-3091-3793
                Article
                molecules-23-02849
                10.3390/molecules23112849
                6278347
                30400134
                71872b81-ef11-4313-8b85-1135d912bc29
                © 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
                : 04 July 2018
                : 07 September 2018
                Categories
                Review

                pamam,dendrimers,drug delivery,gene delivery,nanotechnology
                pamam, dendrimers, drug delivery, gene delivery, nanotechnology

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