A novel nasal almotriptan loaded solid lipid nanoparticles in mucoadhesive in situ gel formulation for brain targeting: Preparation, characterization and in vivo evaluation
A novel nasal almotriptan loaded solid lipid nanoparticles in mucoadhesive in situ gel formulation for brain targeting: Preparation, characterization and in vivo evaluation
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DOI：
10.1016/j.ijpharm.2018.07.014
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发表时间：
2018-09-01
影响因子：
5.8
通讯作者：
Boraie, Nabila Ahmed
中科院分区：
文献类型：
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作者：
Abou Youssef, Nancy Abdel Hamid;Kassem, Abeer Ahmed;Boraie, Nabila Ahmed
本工作旨在设计水溶性抗偏头痛药物苹果酸阿莫曲坦（ALM）鼻内（IN）脑靶向的高效安全给药系统。采用w/o/w复乳-溶剂挥发法制备固体脂质纳米粒。基于评价粒径（PS）、多分散指数（PDI）和包封率（%EE）选择最佳SLN处方。优化的配方表现出可接受的范围; PS为207.9 nm，PDI为0.41，%EE为50.81%。评价不同浓度（16%、18%、20%w/v）的泊洛沙姆407（Plx）与不同粘膜粘附聚合物（Carbopol-974 P、海藻酸钠、Na-CMC）的胶凝时间和温度、pH和粘膜粘附。选择的粘膜粘附原位凝胶配方;基于18%Plx 407的-0.75%w/v Na-CMC，显示出可接受的结果，使得优化的SLN配方进一步分散在其中，并评价体外释放、稳定性、体内和药代动力学研究。同时进行生物标志物评价和组织病理学检查。结果显示优化配方的快速ALM脑递送; NF（基于SLN的IN原位凝胶）、ND（游离ALM IN原位凝胶）和ALM静脉内（ALM IV溶液）在10分钟时的脑/血液比分别为0.89、0.19和0.31。毒理学结果证实了NF经鼻给药的安全性。所取得的成果对于在未来的研究中开发的系统在人类中的进一步临床试验是令人鼓舞的。
This work aimed at designing efficient safe delivery system for intranasal (IN) brain targeting of the water soluble anti-migraine drug Almotriptan malate (ALM). Solid lipid nanoparticles (SLNs) were prepared by w/o/w double emulsion-solvent evaporation method. Selection of the optimized SLNs formula was based on evaluating particle size (PS), poly dispersity index (PDI) and entrapment efficiency (%EE). Optimized formula exhibited acceptable ranges; PS of 207.9 nm, PDI of 0.41 and %EE of 50.81%. Poloxamer 407 (Plx) at different concentrations (16%, 18%, 20% w/v), with different mucoadhesive polymers (Carbopol-974P, Na alginate, Na-CMC) were evaluated for gelling time and temperature, pH and mucoadhesion. The chosen mucoadhesive in-situ gel formula; 18% Plx 407 based-0.75%w/v Na-CMC, showed acceptable results, so that the optimized SLNs formula was further dispersed in it and evaluated for in vitro release, stability, in vivo and pharmacokinetics studies. Biomarkers' evaluation and histopathological examination were also investigated. Results revealed rapid ALM brain delivery of the optimized formula; Brain/blood ratios at 10 min. for NF (SLNs based IN in-situ gel), ND (Free ALM IN in situ gel) and ALM i.v. (ALM IV solution) were 0.89, 0.19 and 0.31, respectively. Toxicological results confirmed the safety of NF for nasal administration. The achieved out comings are encouraging for further clinical trials of the developed system in humans in future research.