Sodium alginate를 이용하여 제조한 alginate bead에 음이온성 약물인 sodium salicylate와 양이온성 약물인 lidocaine·HCl을 함유(loading)시키고, 약물이 함유된 bead의 방출특성을 개선하기 위하여, 자외선과 glutaraldehyde로 각각 bead의 표면을 가교시켰으며, chitosan으로 표면을 coating시켜 약물방출실험을 행하였다. 약물방출실험결과 음이온성 약물의 경우 표면처리 방법에 대해 glutaraldehyde crosslinking, chitosan coating, U.V. crosslinking bead의 순서로, 그리고 alginate 농도에 대해서는 2%, 3%, 4%의 순서로 약물의 방출량이 증가하였으며, 양이온성 약물의 방출경향은 bead 표면처리에 대해서는 음이온성 약물과 같은 경향을 보였으나, alginate 농도변화에 대해서는 음이온성 약물으 경우와 반대로, 4%, 3%, 2%의 순서로 방출량이 증가하는 결과를 보였다. 또한 양이온성 약물의 경우 최종 방출량이 전체적으로 음이온성 약물에 비해 50% 정도에 그쳤는 바, 이러한 차이는 bead와 약물간의 정전기적 상호작용 때문이었다. Glutaraldehyde crosslinking bead의 경우에는 약물의 전하와 상관없이 zero order의 좋은 방출특성을 보여 본 실험에서의 alginate bead에 대한 표면처리방법 중 가장 우수한 것으로 나타났다.

For the controlled release of drug, beads were prepared using sodium alginate which is bioerodible natural polymer. Drugs which have different ionic charge, sodium salicylate and lidocaine·HCl, were loaded into beads via swelling loading method. The surface of beads was modified by ultra-violet crosslinking, chitosan coating and glutaraldehyde crosslinking, respectively. To examine the effects of ionic charge of drugs and surface modification on release characteristics, release experiments of sodium salicylate and lidocaine·HCl from unmodified and three modified beads were carried out. Released amount of anionic drug, sodium salicylate was increased with the increase in the amount of alginate in bead, due to ionic repulsive force between anionic charges of alginate and sodium salicylate. For the case of cationic drug, lidocaine·HCl, released amount is decreased with the increase in alginate concentration for electrostatic attractive force between alginate and lidocaine·HCl. Among the three surface modified beads, surface crosslinking with glutaraldehyde beads showed zero-order release kinetics for both anionic and cationic drugs.

Alginate Glutaraldehyde Crosslinking Ionic Drug

Lunt OR, J. Agric. Food Chem., 19, 797 (1971)
Folkman J, Long DM, J. Surg. Res., 4, 139 (1964) 
Desal SJ, Simonelil AP, Higuchi WI, J. Pharm. Sci., 54 (1965)
Langer R, Folkman J, Nature, 263, 797 (1976) 
Rosen HB, Kohn J, Leong K, Langer R, "Controlled Release Systems," Fabrication Technology," Hsieh, D. Ed., CRC Press Boca Raton, 2 (1988)
Illum L, Davis SS, "Polymers in Controlled Drug Delivery," Wright, Bristol (1987)
Langer R, Peppas N, J. Macromol. Sci., 23, 61 (1983)
Haug A, Smidsrod O, Acta Chem. Scand., 19, 341 (1967)
Salib NN, El-Menshawy MA, Ismail AA, Pharm. Ind., 40, 1230 (1978)
Rak J, Chalaabata M, Heinrich J, Antoninova K, Farm. Ohz., 53, 309 (1984)
Badwan AA, Abumalooh A, Sallam E, Abuhalaf A, Jawan A, Drug Dev. Ind. Pharm., 11, 239 (1985)
Chowdary PK, Suresh KV, J. Pharm. Sci., 50, 173 (1988) 
Xi N, Tu Z, Pei Y, Uui D, Ma L, Yao Hsueh Hsueh Pao., 16, 277 (1981)
Simon LD, Ruizcardona L, Topp EM, Stella VJ, Drug Dev. Ind. Pharm., 20(15), 2341 (1994)
Polk A, Amsden B, Deyao K, Peng T, Goosen MFA, J. Pharm. Sci., 83, 178 (1994) 
Iannuccelli V, Coppi G, Vandelli MA, Leo E, Bernabei MT, Drug Dev. Ind. Pharm., 21(20), 2307 (1995)
Kim JH, Shim JK, Lee YM, Son TI, Membr. J., 3(2), 70 (1993)
Ko C, Dixit V, Shaw W, Gitnick G, Artificial Cells Blood Sunstitutes and Immobilization Biotechnology, 23(2), 143 (1995)
Miyazaki S, Nakayama A, Oda M, Tanaka M, Attwood D, Biological Pharm. Bull., 17(5), 745 (1994)