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      Self-Assembled Hydrogel Nanoparticles for Drug Delivery Applications

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          Abstract

          Hydrogel nanoparticles—also referred to as polymeric nanogels or macromolecular micelles—are emerging as promising drug carriers for therapeutic applications. These nanostructures hold versatility and properties suitable for the delivery of bioactive molecules, namely of biopharmaceuticals. This article reviews the latest developments in the use of self-assembled polymeric nanogels for drug delivery applications, including small molecular weight drugs, proteins, peptides, oligosaccharides, vaccines and nucleic acids. The materials and techniques used in the development of self-assembling nanogels are also described.

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          A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs.

          Y Matsumura, H. Maeda (1986)
          We previously found that a polymer conjugated to the anticancer protein neocarzinostatin, named smancs, accumulated more in tumor tissues than did neocarzinostatin. To determine the general mechanism of this tumoritropic accumulation of smancs and other proteins, we used radioactive (51Cr-labeled) proteins of various molecular sizes (Mr 12,000 to 160,000) and other properties. In addition, we used dye-complexed serum albumin to visualize the accumulation in tumors of tumor-bearing mice. Many proteins progressively accumulated in the tumor tissues of these mice, and a ratio of the protein concentration in the tumor to that in the blood of 5 was obtained within 19 to 72 h. A large protein like immunoglobulin G required a longer time to reach this value of 5. The protein concentration ratio in the tumor to that in the blood of neither 1 nor 5 was achieved with neocarzinostatin, a representative of a small protein (Mr 12,000) in all time. We speculate that the tumoritropic accumulation of these proteins resulted because of the hypervasculature, an enhanced permeability to even macromolecules, and little recovery through either blood vessels or lymphatic vessels. This accumulation of macromolecules in the tumor was also found after i.v. injection of an albumin-dye complex (Mr 69,000), as well as after injection into normal and tumor tissues. The complex was retained only by tumor tissue for prolonged periods. There was little lymphatic recovery of macromolecules from tumor tissue. The present finding is of potential value in macromolecular tumor therapeutics and diagnosis.
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            Nanomedicine: current status and future prospects.

            S Moein Moghimi, J Clifford Murray, J. Clifford Murray (2005)
            Applications of nanotechnology for treatment, diagnosis, monitoring, and control of biological systems has recently been referred to as "nanomedicine" by the National Institutes of Health. Research into the rational delivery and targeting of pharmaceutical, therapeutic, and diagnostic agents is at the forefront of projects in nanomedicine. These involve the identification of precise targets (cells and receptors) related to specific clinical conditions and choice of the appropriate nanocarriers to achieve the required responses while minimizing the side effects. Mononuclear phagocytes, dendritic cells, endothelial cells, and cancers (tumor cells, as well as tumor neovasculature) are key targets. Today, nanotechnology and nanoscience approaches to particle design and formulation are beginning to expand the market for many drugs and are forming the basis for a highly profitable niche within the industry, but some predicted benefits are hyped. This article will highlight rational approaches in design and surface engineering of nanoscale vehicles and entities for site-specific drug delivery and medical imaging after parenteral administration. Potential pitfalls or side effects associated with nanoparticles are also discussed.
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              Long-circulating and target-specific nanoparticles: theory to practice.

              S M Moghimi, A C Hunter, J C Murray (2001)
              The rapid recognition of intravenously injected colloidal carriers, such as liposomes and polymeric nanospheres from the blood by Kupffer cells, has initiated a surge of development for "Kupffer cell-evading" or long-circulating particles. Such carriers have applications in vascular drug delivery and release, site-specific targeting (passive as well as active targeting), as well as transfusion medicine. In this article we have critically reviewed and assessed the rational approaches in the design as well as the biological performance of such constructs. For engineering and design of long-circulating carriers, we have taken a lead from nature. Here, we have explored the surface mechanisms, which affords red blood cells long-circulatory lives and the ability of specific microorganisms to evade macrophage recognition. Our analysis is then centered where such strategies have been translated and fabricated to design a wide range of particulate carriers (e.g., nanospheres, liposomes, micelles, oil-in-water emulsions) with prolonged circulation and/or target specificity. With regard to the targeting issues, attention is particularly focused on the importance of physiological barriers and disease states.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Materials (Basel)
                Journal ID (iso-abbrev): Materials (Basel)
                Journal ID (publisher-id): materials
                Title: Materials
                Publisher: Molecular Diversity Preservation International
                ISSN (Electronic): 1996-1944
                Publication date (Electronic): 24 February 2010
                Publication date Collection: February 2010
                Volume: 3
                Issue: 2
                Pages: 1420-1460
                Affiliations
                IBB-Institute for Biotechnology and Bioengineering, Centre for Biological Engineering, Minho University, Campus de Gualtar 4710-057, Braga, Portugal; E-Mails: cgoncalves@ 123456deb.uminho.pt (C.G.); paulapereira@ 123456deb.uminho.pt (P.P.)
                Author notes
                [* ] Author to whom correspondence should be addressed; E-Mail: fmgama@ 123456deb.uminho.pt ; Tel.: +351 253 604 400; Fax: +351 253 678 986.
                Article
                Publisher ID: materials-03-01420
                DOI: 10.3390/ma3021420
                PMC ID: 5513474
                SO-VID: 425c855e-b8d6-4a63-b372-ac6fbc507ab2
                Copyright © © 2010 by the authors;
                License:

                licensee Molecular Diversity Preservation International, Basel, Switzerland. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                Date received : 13 January 2010
                Date revision received : 04 February 2010
                Date accepted : 21 February 2010
                Categories
                Subject: Review

                Keywords: polymer,delivery,targeting,self-assembly,drugs
                Data availability:
                Keywords: polymer, delivery, targeting, self-assembly, drugs

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