ALBUMIN HEPARIN MICROSPHERES AS CARRIERS FOR CYTOSTATIC AGENTS

被引：33

作者：

CREMERS, HFM

FEIJEN, J

KWON, G

BAE, YH

KIM, SW

NOTEBORN, HPJM

MCVIE, JG

机构：

[1] Department of Chemical Technology, University of Twente, P. O. Box 217

[2] Department of Pharmaceutics, University of Utah, Salt Lake City

[3] Department of Experimental Therapy, Netherlands Cancer Institute, Plesmanlaan 12 1

来源：

JOURNAL OF CONTROLLED RELEASE | 1990年 / 11卷 / 1-3期

关键词：

adriamycin; albumin-heparin conjugate; chemoembolization; ion-exchange hydrogels; microspheres;

D O I：

10.1016/0168-3659(90)90130-L

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Much work has been done on adriamycin-loaded albumin microspheres (Alb-MS) for chemoembolization [1-4], the rationale being that site-specific drug delivery may increase the therapeutic efficacy of the drug. Alb-Ms are being investigated because of their biocompatibility and because the degradation products of these microspheres are non-toxic. However, these microspheres have some disadvantages (i.e. drug loading during the microsphere preparation, low payloads, large burst effects). These disadvantages can be overcome by the incorporation of heparin (a highly negatively charged mucopolysaccharide). Albumin-heparin microspheres were prepared (i) by crosslinking of soluble albumin and heparin first using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and subsequently glutaraldehyde (Alb-Hep-MS) and (ii) by crosslinking a preformed soluble conjugate of heparin and albumin with glutaraldehyde (Alb-Hep-Conj-MS). Albumin-heparin microspheres could be loaded with adriamycin after microsphere preparation giving payloads of 15-30%. Preliminary in vitro adriamycin release experiments showed that Alb-Hep-Conj-MS exhibit sustained release properties. Furthermore ion-exchange properties could be observed both with Alb-Hep-MS and Alb-Hep-Conj-MS. In vitro and in vivo toxicity experiments with Alb-Hep-MS showed no adverse effects. © 1990.

引用

页码：167 / 179

页数：13

共 20 条

[1] Senyei, Driscoll, Widder, Biophysical drug targeting: Magnetically responsive albumin microspheres, Meth. Enzymol., 112, pp. 56-67, (1985)
[2] Longo, Goldberg, Hydrophilic albumin microspheres, Meth. Enzymol., 112, pp. 18-27, (1985)
[3] Gupta, Gallo, Hung, Perrier, Influence of stabilization temperature on the entrapment of adriamycin in albumin microspheres, Drug Dev. Ind. Pharm., 13, pp. 1471-1482, (1987)
[4] MacArdle, Lewi, Hansell, Kerr, McKillop, Willmott, Cytotoxic-loaded albumin microspheres: A novel approach to regional chemotherapy, Br. J. Surg., 75, pp. 132-134, (1988)
[5] Kramer, Albumin microspheres as vehicles for achieving specificity in drug delivery, J. Pharm. Sci., 63, pp. 1646-1647, (1974)
[6] Goosen, Leung, O'Shea, Clou, Sun, Slow release of insulin from a biodegradable matrix implanted in diabetic rats, Diabetes, 32, pp. 478-481, (1983)
[7] Burgess, Davis, Tomlinson, Potential use of albumin microspheres as a drug delivery system. I. Preparation and in vivo release of steroids, Int. J. Pharm., 39, pp. 129-136, (1987)
[8] Yapel, Albumin microspheres: Heat and chemical stabilization, Meth. Enzymol., 112, pp. 3-18, (1985)
[9] Davis, Mills, Tomlinson, Chemically cross-linked albumin microspheres for the controlled release of incorporated rose bengal after intramuscular injection into rabbits, J. Controlled Release, 4, pp. 293-302, (1987)
[10] Fujimoto, Miyazaki, Endoh, Takahashi, Shrestha, Okui, Morimoto, Terao, Effects of intra-arterially infused biodegradable microspheres containing mitomycin C, Cancer, 55, pp. 522-526, (1985)

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