A novel nanogel loaded with chitosan decorated bilosomes for transdermal delivery of terbutaline sulfate: artificial neural network optimization, in vitro characterization and in vivo evaluation
A novel nanogel loaded with chitosan decorated bilosomes for transdermal delivery of terbutaline sulfate: artificial neural network optimization, in vitro characterization and in vivo evaluation
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DOI：
10.1007/s13346-019-00688-1
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发表时间：
2019-11-01
影响因子：
5.4
通讯作者：
Abdeltwab, Amany M.
中科院分区：
文献类型：
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作者：
El Menshawe, Shahira F.;Aboud, Heba M.;Abdeltwab, Amany M.
本工作的目的是制备、优化和评价硫酸特布他林(TBN)透皮透皮双糖体(BLS)，并与传统的特布他林口服溶液和游离TBN透皮凝胶进行比较，以避免肝脏首过代谢。采用以面为中心的中心组合设计，考察不同配方变量对TBN-BLS的影响，并利用人工神经网络(ANN)模型对TBN-BLS进行优化。以大豆磷脂酰胆碱和胆固醇为脂相，脱氧胆酸钠(SDC)为表面活性剂，分别在壳聚糖(CTS)包覆和壳聚糖(CTS)包覆的条件下，采用薄膜水合法制备了TBN-BLS。在进行了理化鉴定后，将其用于大鼠模型的组织病理学研究和药代动力学研究。优化后的壳聚糖包衣双体为球形囊泡(245.13+/-10.23 nm)，具有较好的包封率(65.25+/-5.51%)和良好的渗透特性(340.11+/-22.34mgcm2)。TBN-CTS-BLS凝胶制剂耐受性良好，在组织病理学评估中没有表现出炎症迹象。药代动力学研究表明，与口服制剂相比，优化处方的生物利用度提高约2.33倍，t(1/2)增加至约6.21+/-0.24 h。这些结果支持了BLS作为TBN活性和安全的透皮载体在哮喘治疗中的应用前景。
The objective of the present work was to formulate, optimize, and evaluate transdermal terbutaline sulfate (TBN)-loaded bilosomes (BLS) in gel, compared to conventional oral TBN solution and transdermal gel loaded with free TBN, aiming at evading the hepatic first-pass metabolism. A face-centered central composite design was adopted to observe the effects of different formulation variables on TBN-BLS, and artificial neural network (ANN) modeling was employed to optimize TBN-BLS. TBN-BLS were prepared by a thin film hydration method integrating soybean phosphatidylcholine and cholesterol as a lipid phase and sodium deoxycholate (SDC) as a surfactant with or without the coating of chitosan (CTS). After being subjected to physicochemical characterization, TBN-BLS were enrolled in a histopathological study and pharmacokinetic investigation in a rat model. The optimized TBN chitosan-coated bilosomes (TBN-CTS-BLS) were spherical vesicles (245.13 +/- 10.23 nm) with adequate entrapment efficiency (65.25 +/- 5.51%) and good permeation characteristics (340.11 +/- 22.34 mu g/cm(2)). The TBN-CTS-BLS gel formulation was well-tolerated with no inflammatory signs manifested upon histopathological evaluation. The pharmacokinetic study revealed that the optimized TBN-CTS-BLS formulation successively enhanced the bioavailability of TBN by about 2.33-fold and increased t(1/2) to about 6.21 +/- 0.24 h as compared to the oral solution. These findings support the prospect use of BLS as active and safe transdermal carrier for TBN in the treatment of asthma.