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KMID : 0361020010440070748
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Korean Journal of Otolaryngology - Head and Neck Surgery
2001 Volume.44 No. 7 p.748 ~ p.753
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Regulation of Cell Differentiation and Growth in Head and Neck Squamous Cell Carcinoma by Biodegradable Microsphere Including Retinoic Acid
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안중호/Joong Ho Ahn
변영로/최용두/남순열/유승주/김상윤/Youngro Byun/Yongdoo Choi/Soon Yhl Nam/Seung Joo Yoo/Sang Yoon Kim
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Abstract
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Background and Objectives : It has been known that retinoids including all-trans-retinoic acid (atRA) play an essential role in the regulation of cell differentiation and growth. But its clinical application is limited due toe the induced
metabolism by
specific P450's in the liver. We prepared atRA containing biodegradable microspheres to reduce the metabolism and to maintain the therapeutic blood concentration with low toxicity. Materials and Methods : Microsphere containing atRA(PLE8/atRA4
MS)
was
prepared. One million AMC-HN-4 cells (head and neck squamous carcinoma cell line ; HNSCC) were injected subcutaneously on the backs of nude mice. On the same day, 100 mg atRA/kg of microspheres were injected subcutaneously into athymic nude mice.
Tumor
size was measured weekly. Results : Cumulative released amount of atRA according to the amount of atRA load was calculated. Two percent and four percent atRA loaded microspheres showed lst degree and 0-degree releasing curves,
respectively.
Eight-percent atRA loaded microsphere showed an irregular release pattern. One time injection of PLE8/atRA4 (100 mg atRA/kg) MS decreased the tumor size up to 80% during 5 weeks. Conclusions : Our results suggest that microspheres containing atRa
may be
a good drug delivery system for the clinical application of atRa. However, this study was performed only in nude mice, so, a further study using immunogenic animals will be needed for the clinical application of these microspheres.
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KEYWORD
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