Formulation and characterization of 5-Fluorouracil enteric coated nanoparticles for sustained and localized release in treating colorectal cancer.
Formulation and characterization of 5-Fluorouracil enteric coated nanoparticles for sustained and localized release in treating colorectal cancer.
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DOI：
10.1016/j.jsps.2014.11.010
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发表时间：
2015-07
影响因子：
4.1
通讯作者：
Prakash, Ashwati
中科院分区：
文献类型：
--
作者：
Tummala, Shashank;Kumar, M. N. Satish;Prakash, Ashwati
5-氟尿嘧啶沿着奥沙利铂作为一线治疗药物用于结直肠癌的治疗，但其缺乏部位特异性，疗效不佳。此外，对健康细胞的毒性作用和结肠区域大部分药物的不可用性仍然是限制。通过制备肠溶壳聚糖聚合物纳米粒，可直接递送至大肠，从而实现预防毒性作用和药物在结肠区域的定位。肠溶包衣有助于防止药物在胃内pH下降解。因此，本研究采用溶剂蒸发乳化法制备不同比例（1：1，1：2，1：3，1：4）的壳聚糖聚合物纳米粒。采用差示扫描量热法（DSC）、X射线衍射法（XRD）、包封率和粒径对优化的聚合物比例进行表征，并进一步进行肠溶包衣。体外药物释放研究使用透析袋技术进行，使用不同pH值（1.2、4.5、7.5、7.0）的模拟流体模拟GIT道。药物与聚合物比例为1：2和1：3的5-FU纳米粒具有较好的粒径（分别为149 ± 1.28 nm和138 ± 1.01 nm）、包封率（分别为48.12 ± 0.08%和69.18 ± 1.89）。5-FU E1在4小时后显示出更好的药物释放，并且以与非肠溶包衣片剂相当的持续方式显示出82%的药物释放，直到24小时，非肠溶包衣片剂在进入结肠区域之前释放超过50%的药物。因此，我们可以得出结论，通过这种方法使用相同的聚合物以优化的比例制备的纳米颗粒可以代表潜在的药物递送方法，用于有效地将活性药物成分递送至结直肠肿瘤。
5-Fluorouracil is used in the treatment of colorectal cancer along with oxaliplatin as first line treatment, but it is having lack of site specificity and poor therapeutic effect. Also toxic effects to healthy cells and unavailability of major proportion of drug at the colon region remain as limitations. Toxic effects prevention and drug localization at colon area was achieved by preparing enteric-coated chitosan polymeric nanoparticles as it can be delivered directly to large bowel. Enteric coating helps in preventing the drug degradation at gastric pH. So the main objective was to prepare chitosan polymeric nanoparticles by solvent evaporation emulsification method by using different ratios of polymer (1:1, 1:2, 1:3, 1:4). Optimized polymer ratio was characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), entrapment efficiency and particle size and further subjected to enteric coating. In vitro drug release studies were done using dialysis bag technique using simulated fluids at various pH (1.2, 4.5, 7.5, 7.0) to mimic the GIT tract. 5-FU nanoparticles with drug: polymer ratio of 1:2 and 1:3 has shown better particle size (149 ± 1.28 nm and 138 ± 1.01 nm respectively), entrapment efficiency (48.12 ± 0.08% and 69.18 ± 1.89 respectively). 5-FU E1 has shown better drug release after 4 h and has shown 82% drug release till 24 h in a sustained manner comparable to the non-enteric coated tablets, which released more than 50% of the drug before entering the colon region. So we can conclude that nanoparticles prepared by this method using the same polymer with the optimized ratio can represent as potential drug delivery approach for effective delivery of the active pharmaceutical ingredient to the colorectal tumors.
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DOI：
10.3390/molecules13081551
发表时间：
2008-08-05
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Zhang N;Yin Y;Xu SJ;Chen WS
通讯作者：
Chen WS
影响因子：
45.3
作者：
Ramanathan, RK;Clark, JW;Kardinal, CG
通讯作者：
Kardinal, CG
DOI：
10.1016/j.nano.2009.03.002
发表时间：
2010-02-01
影响因子：
5.4
作者：
Jain, Anekant;Jain, Sanjay K.;Beg, Aadil M.
通讯作者：
Beg, Aadil M.
影响因子：
5.8
作者：
Arias, Jose L.;Adolfina Ruiz, M.;Delgado, Angel V.
通讯作者：
Delgado, Angel V.
影响因子：
4.6
作者：
Cirstoiu-Hapca, A.;Buchegger, F.;Delie, F.
通讯作者：
Delie, F.