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      Adsorption and Desorption of Bioactive Proteins on Hydroxyapatite for Protein Delivery Systems

      research-article
      1 , * , 2
      Journal of Drug Delivery
      Hindawi Publishing Corporation

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          Abstract

          Hydroxyapatite (HA) is a precursor of bone and has been studied as a biomaterial. We attempted HA to apply to protein delivery systems. In this study, the association and dissociation properties of two types of bioactive proteins, cytochrom c and insulin, to HA were investigated. Cytochrom c was less associated with HA than insulin, which was easily released from it. However, the release of insulin from HA was slow. Insulin was released from HA at pH 7.4 more rapidly than at pH 3. The association and dissociation properties might be influenced by the size, solubility and net charge of protein. HA is a potential protein carrier with controlled release.

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          Most cited references15

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          Polymer therapeutics: concepts and applications.

          Polymer therapeutics encompass polymer-protein conjugates, drug-polymer conjugates, and supramolecular drug-delivery systems. Numerous polymer-protein conjugates with improved stability and pharmacokinetic properties have been developed, for example, by anchoring enzymes or biologically relevant proteins to polyethylene glycol components (PEGylation). Several polymer-protein conjugates have received market approval, for example the PEGylated form of adenosine deaminase. Coupling low-molecular-weight anticancer drugs to high-molecular-weight polymers through a cleavable linker is an effective method for improving the therapeutic index of clinically established agents, and the first candidates have been evaluated in clinical trials, including, N-(2-hydroxypropyl)methacrylamide conjugates of doxorubicin, camptothecin, paclitaxel, and platinum(II) complexes. Another class of polymer therapeutics are drug-delivery systems based on well-defined multivalent and dendritic polymers. These include polyanionic polymers for the inhibition of virus attachment, polycationic complexes with DNA or RNA (polyplexes), and dendritic core-shell architectures for the encapsulation of drugs. In this Review an overview of polymer therapeutics is presented with a focus on concepts and examples that characterize the salient features of the drug-delivery systems.
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            Responsive polymeric delivery systems.

            This paper discusses the state of the art in a relatively new approach in the field of controlled drug delivery-responsive polymeric drug delivery systems. Such systems are capable of adjusting drug release rates in response to a physiological need. The fundamental principles of externally and self-regulated delivery systems are examined. Special attention is paid to specific clinical settings such as diabetes, presenting the advantages and disadvantages of different approaches.
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              Hydroxyapatite particles as a controlled release carrier of protein.

              This study examines the possibility of using hydroxyapatite (HAp) particles as a controlled release carrier of protein. In order to achieve effective protein release from HAp particles, it is necessary to regulate the conjugated amount of protein on HAp and the resorption of HAp. HAp particles were synthesized at different temperatures (40 degrees C, 60 degrees C, 80 degrees C) in wet condition and the physico-chemical properties of synthesized HAp particles were examined. HAp particles synthesized at low temperatures showed low crystallinity, high solubility and large specific surface area. The useful growth factors for bone regeneration, such as BMP, bFGF and TGF-beta, are basic proteins, so cytochrome c (pI=10.2) was used as a model protein and the adsorptive property of protein on HAp particles was investigated. The protein adsorption on HAp particles changed depending on its specific surface area and the chart of protein adsorption on HAp particles showed a typical Langmuir curve. These findings suggest that the adsorbed amount of protein on HAp particles could be regulated by HAp synthesizing temperature and the concentrations of protein solution. The release kinetics of protein from the HAp particles that adsorbed the protein (HAp-pro) was also evaluated in different pH solutions (pH 4.0 and 7.0). The released protein gradually increased time dependently when HAp-pro were immersed in pH 4.0 solution, but the released protein was significantly smaller when HAp-pro were immersed in pH 7.0 solution. Moreover, the release rate of protein from HAp-pro differed in each HAp that was synthesized at different temperatures, suggesting that the release of protein from HAp-pro depended on HAp resorption. These results suggest that HAp particles synthesized at different temperature are useful as a controlled release carrier of protein.
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                Author and article information

                Journal
                J Drug Deliv
                J Drug Deliv
                JDD
                Journal of Drug Delivery
                Hindawi Publishing Corporation
                2090-3014
                2090-3022
                2012
                5 March 2012
                : 2012
                : 932461
                Affiliations
                1Nanoscience and Nanotechnology Research Center, Research Organization for the 21st Century, Osaka Prefecture University, 1-2 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8570, Japan
                2Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan
                Author notes

                Academic Editor: Jia You Fang

                Article
                10.1155/2012/932461
                3312276
                22506125
                6b59685e-9839-49ed-a982-6eac954679e1
                Copyright © 2012 C. Kojima and K. Watanabe.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 14 November 2011
                : 16 December 2011
                Categories
                Research Article

                Pharmaceutical chemistry
                Pharmaceutical chemistry

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