Release properties of bovine serum albumin (BSA) and egg white lysozyme (LSZ) on hydroxyapatite containing carbonate ion (CHAp) of various contents were examined with our new flow experimental system. The desorption ratio: the r de , defined as the ratio of desorbed amount to initially-adsorbed one, was employed as an index of binding strength of these proteins to the surface. Dependency of the content of the carbonate ion on the r de showed reverse tendency for BSA and LSZ; the r de of BSA increased as an increase of content of the carbonate ion, while that of LSZ decreased as the increase of the content. This result clarified a difference of primary adsorption sites between BSA and LSZ. As incorporation of the carbonate ion into apatite retarded the growth of the crystal along the c axis, the exposed area of the c face, i.e. the primary adsorption site of LSZ, the p site increased and that of the a (b) face, i.e. the primary site of BSA, the c site decreased.
A new flow experimental system was employed in order to obtain relevant information about the capability of hydroxyapatite as a drug-delivery carrier in vitro rather than in batch systems. Using our system, we were able to estimate and monitor continuously both the adsorbed and desorbed amounts of protein and the dynamic adsorption and desorption behavior, indicating that this system is a promising technique for evaluating the drug-release properties of ceramic materials.©2010 The Ceramic Society of Japan. All rights reserved.Key-words : Carbonate ion-containing apatite, Drug-delivery carrier, Adsorption and desorption behavior of protein, Flow system, Bovine serum albumin [Received January 8, 2010; Accepted March 23, 2010] Drug delivery systems (DDSs) have been a key medical technology used for improving the quality of life in patients by prolonging the effective period and decreasing side effects of a drug. There are three main approaches to DDS: (1) target the affected part with a pro-drug, which is a chemically-modified drug precursor (2) improve drug absorption with a adsorption promoter, an inhibitor of digestive enzyme and (3) control drug release by chemical modification or by loading onto a carrier. 1)Research into the use of ceramic materials as drug carriers was initiated in the 1980s, 2) and recently, hydroxyapatite (HAp) has been investigated as a controlled-release carrier for various drugs such as proteins, 3),4) hormones, 5),6) bisphosphonates 7) (for use in osteoporosis), antimicrobial metal ions, 8) and antitumor drugs. 9)In most studies, in vitro drug-release behavior was examined in batch systems. We followed the adsorption and desorption behavior of proteins on HAp with different carbonate-ion contents (CHAp) 10) in a batch system, and observed that readsorption occurred several hours after desorption from CHAp. This static situation, however, differs greatly from the real-life biological environment, for example, in which a drug is exposed to fluid in the vascular system. Therefore, we attempted to apply an in vitro flow system, in which protein-loaded CHAp powder was exposed to fluid, to allow us to follow the desorption behavior of proteins in order to investigate the drug-release capability of CHAp. We also compared the results from the flow system with those from the batch system.The different carbonate-ion content CHAps were prepared by adding 0.06 M (NH 4 ) 2 HPO 4 and 0.06 M NH 4 HCO 3 aqueous solution to 0.1 M Ca(NO 3 ) 2 ·4H 2 O aqueous solution under controlled pH levels of 6.0, 7.0, 8.5, or 10.5. The detailed procedure has been described in a previous paper.11) The carbonate-ion content was less than 10 mass % in each case, which is comparable to the content in biologically occurring HAp.12) The CHAps containing the lowest and highest carbonateion content were chosen in order to compare the effect of modifying the carbonate ion on the adsorption and desorption properties of the protein. Two physical and chemical differences were observed between the two CHAp types: the CHAp wi...
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