Injectable in situ cross-linking hydrogels for local antifungal therapy.
Injectable in situ cross-linking hydrogels for local antifungal therapy.
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DOI：
10.1016/j.biomaterials.2009.11.016
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发表时间：
2010-02
期刊：
影响因子：
14
通讯作者：
Kohane, Daniel S.
中科院分区：
文献类型：
--
作者：
Hudson, Sarah P.;Langer, Robert;Fink, Gerald R.;Kohane, Daniel S.
侵袭性真菌感染可能是毁灭性的，特别是在免疫功能低下的患者中，并且难以用全身药物治疗。此外，全身服用这些药物可能会产生严重的副作用。我们开发了一种可注射的局部抗真菌治疗方法，可直接给药到现有或潜在的真菌感染部位。两性霉素B （AmB）是一种疏水、强效、广谱的抗真菌剂，通过与右旋糖酐醛聚合物的偶联使其具有水溶性。葡聚糖-醛- amb偶联物对白色念珠菌保持抗真菌作用。将羧甲基纤维素-肼与葡聚糖-醛混合形成凝胶，通过形成腙键在原位交联。凝胶体外释放抗真菌活性11天，与凝胶接触杀死念珠菌3周。小鼠腹膜无明显组织毒性，凝胶无粘连。将AmB悬浮液包埋在cmc -葡聚糖中而不将药物与聚合物偶联而产生的凝胶不会释放出杀真菌活性，但在接触时确实会杀死。这些类型的可注射系统，含有可溶性或不溶性药物制剂，可用于治疗局部抗真菌感染，或不同时进行全身治疗。
Invasive fungal infections can be devastating, particularly in immunocompromised patients, and difficult to treat with systemic drugs. Furthermore, systemic administration of those medications can have severe side effects. We have developed an injectable local antifungal treatment for direct administration into existing or potential sites of fungal infection. Amphotericin B (AmB), a hydrophobic, potent, and broad-spectrum antifungal agent, was rendered water-soluble by conjugation to a dextran-aldehyde polymer. The dextran-aldehyde-AmB conjugate retained antifungal efficacy against C. albicans. Mixing carboxymethylcellulose-hydrazide with dextran-aldehyde formed a gel that cross-linked in situ by formation of hydrazone bonds. The gel provided in vitro release of antifungal activity for 11 days, and contact with the gel killed Candida for three weeks. There was no apparent tissue toxicity in the murine peritoneum and the gel caused no adhesions. Gels produced by entrapment of a suspension of AmB in CMC-dextran without conjugation of drug to polymers did not release fungicidal activity, but did kill on contact. Injectable systems of these types, containing soluble or insoluble drug formulations, could be useful for treatment of local antifungal infections, with or without concurrent systemic therapy.
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DOI：
10.1002/jbm.1261
发表时间：
2002-03-05
期刊：
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH
影响因子：
--
作者：
Kohane, DS;Lipp, M;Langer, R
通讯作者：
Langer, R
影响因子：
3.7
作者：
Nishi, K. K.;Antony, M.;Jayakrishnan, A.
通讯作者：
Jayakrishnan, A.
影响因子：
4.9
作者：
BARWICZ, J;CHRISTIAN, S;GRUDA, I
通讯作者：
GRUDA, I
影响因子：
4.6
作者：
BRUNEEL, D;SCHACHT, E
通讯作者：
SCHACHT, E
DOI：
10.1067/s0002-9378(03)00726-9
发表时间：
2003-11-01
影响因子：
9.8
作者：
Sobel, JD;Chaim, W;Leaman, D
通讯作者：
Leaman, D