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      Polymeric Nanoparticles for Drug Delivery: Recent Developments and Future Prospects

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          Abstract

          The complexity of some diseases—as well as the inherent toxicity of certain drugs—has led to an increasing interest in the development and optimization of drug-delivery systems. Polymeric nanoparticles stand out as a key tool to improve drug bioavailability or specific delivery at the site of action. The versatility of polymers makes them potentially ideal for fulfilling the requirements of each particular drug-delivery system. In this review, a summary of the state-of-the-art panorama of polymeric nanoparticles as drug-delivery systems has been conducted, focusing mainly on those applications in which the corresponding disease involves an important morbidity, a considerable reduction in the life quality of patients—or even a high mortality. A revision of the use of polymeric nanoparticles for ocular drug delivery, for cancer diagnosis and treatment, as well as nutraceutical delivery, was carried out, and a short discussion about future prospects of these systems is included.

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          Most cited references191

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          Controlled drug delivery vehicles for cancer treatment and their performance

          Although conventional chemotherapy has been successful to some extent, the main drawbacks of chemotherapy are its poor bioavailability, high-dose requirements, adverse side effects, low therapeutic indices, development of multiple drug resistance, and non-specific targeting. The main aim in the development of drug delivery vehicles is to successfully address these delivery-related problems and carry drugs to the desired sites of therapeutic action while reducing adverse side effects. In this review, we will discuss the different types of materials used as delivery vehicles for chemotherapeutic agents and their structural characteristics that improve the therapeutic efficacy of their drugs and will describe recent scientific advances in the area of chemotherapy, emphasizing challenges in cancer treatments.
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            Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles.

            Albumin is playing an increasing role as a drug carrier in the clinical setting. Principally, three drug delivery technologies can be distinguished: coupling of low-molecular weight drugs to exogenous or endogenous albumin, conjugation with bioactive proteins and encapsulation of drugs into albumin nanoparticles. The accumulation of albumin in solid tumors forms the rationale for developing albumin-based drug delivery systems for tumor targeting. Clinically, a methotrexate-albumin conjugate, an albumin-binding prodrug of doxorubicin, i.e. the (6-maleimido)caproylhydrazone derivative of doxorubicin (DOXO-EMCH), and an albumin paclitaxel nanoparticle (Abraxane) have been evaluated clinically. Abraxane has been approved for treating metastatic breast cancer. An alternative strategy is to bind a therapeutic peptide or protein covalently or physically to albumin to enhance its stability and half-life. This approach has been applied to peptides with antinociceptive, antidiabetes, antitumor or antiviral activity: Levemir, a myristic acid derivative of insulin that binds to the fatty acid binding sites of circulating albumin, has been approved for the treatment of diabetes. Furthermore, Albuferon, a fusion protein of albumin and interferon, is currently being assessed in phase III clinical trials for the treatment of hepatitis C and could become an alternative to pegylated interferon. This review gives an account of the different drug delivery systems which make use of albumin as a drug carrier with a focus on those systems that have reached an advanced stage of preclinical evaluation or that have entered clinical trials.
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              Polymeric drugs for efficient tumor-targeted drug delivery based on EPR-effect.

              For over half a century extensive research has been undertaken for the control of cancer. However, success has been limited to certain malignancies, and surgical intervention is potentially curative for early stage patients. For the majority of patients with advanced stage of cancer, the treatment is limited to chemotherapy or radiation. Chemotherapy in particular has limitations due to the lack of selectivity with severe toxicity. Under these circumstances tumor-targeted delivery of anticancer drugs is perhaps one of the most important steps for cancer chemotherapy. We reported such a drug for the first time, styrene-maleic acid copolymer-conjugated neocarzinostatin (SMANCS) in 1979, and it eventually led to formulate the concept of the enhanced permeability and retention (EPR) effect of solid tumors in 1986. Monoclonal antibody conjugates are another direction, of which interest is increasing recently though with limited success. The EPR-effect appears as a universal phenomenon in solid tumors which warrants the development of other polymeric drugs or nanomedicine. EPR-effect is applicable for any biocompatible macromolecular compounds above 40 kDa, even larger than 800 kDa, or of the size of bacteria; thus complexed molecules like micelles and liposomes containing anticancer drugs are hallmark examples. The drug concentration in tumor compared to that of the blood (T/B ratio) can be usually as high as 10-30 times. In case of SMANCS/Lipiodol given via tumor feeding artery, the T/B ratio can be as high as 2000, a real pin-point targeting. EPR-effect is not just passive targeting for momentary tumor delivery, but it means prolonged drug retention for more than several weeks or longer. This review describes the pathophysiological mechanisms of the EPR-effect, architectural difference of tumor blood vessel, various factors involved and artificial augmentation of EPR-effect with respect to tumor-selective delivery, and then advantages and problems of macromolecular drugs.
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                Author and article information

                Journal
                Nanomaterials (Basel)
                Nanomaterials (Basel)
                nanomaterials
                Nanomaterials
                MDPI
                2079-4991
                19 July 2020
                July 2020
                : 10
                : 7
                : 1403
                Affiliations
                [1 ]Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain; mariapar89@ 123456gmail.com (M.P.-A.); mtnezmun@ 123456gmail.com (G.M.); lolo191995@ 123456gmail.com (M.M.)
                [2 ]Department of Normal and Pathological Cytology and Histology, Faculty of Medicine, University of Seville, 41009 Seville, Spain; tamara.ortiz.cerda@ 123456gmail.com
                [3 ]Department of Microbiology and Parasitology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain
                [4 ]Department of Medicine, Faculty of Medicine, University of Seville, 41009 Seville, Spain; farguelles1@ 123456us.es
                [5 ]Department of Gastroenterology, University Hospital Virgen Macarena, University of Seville, 41009 Seville, Spain
                Author notes
                [* ]Correspondence: bbegines@ 123456us.es (B.B.); aalcudia@ 123456us.es (A.A.)
                Author information
                https://orcid.org/0000-0002-1513-7443
                https://orcid.org/0000-0002-4681-9383
                Article
                nanomaterials-10-01403
                10.3390/nano10071403
                7408012
                32707641
                98bdd471-524f-4665-8279-55fa7fa93716
                © 2020 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
                : 22 June 2020
                : 16 July 2020
                Categories
                Review

                nanoparticles,nanocarriers,polymeric materials,drug-delivery systems,ocular delivery,cancer diagnosis,cancer drug-delivery systems,nutraceuticals

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