Nanosized Intranasal Delivery of Novel Self-Assembled Cubic Liquid Crystals: Formulation and Evaluation

IF 2.7 4区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of Pharmaceutical Innovation Pub Date : 2022-11-12 DOI:10.1007/s12247-022-09695-1

Gurudatta N. Desai, Panchaxari M. Dandagi, Taufik M. Kazi

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引用次数: 1

Abstract

Purpose

The focus of this research was to develop Almotriptan malate (ALM)-loaded cubosomal in situ gel to improve its permeation through the blood–brain barrier (BBB) with an efficient and quick action when administered through the intranasal route.

Method

Cubosomes were developed by emulsifying and homogenizing various proportions and concentrations of pluronics F127 (PF127) and glyceryl monooleate (GMO) along with polyvinyl alcohol (PVA) as suggested by the Box–Behnken design (BBD). The desirability function was used to select the optimum cubosomal formula. The developed cubosomes morphology was validated by high resolution transmission electron microscopy (HR-TEM) analysis. Differential scanning calorimetry (DSC) peaks served as proof that the drug was enclosed within the nanocarrier system. A range of concentrations of PF127 (15–21% w/v) were used to formulate and optimize the in situ gel. Ex vivo permeation experiments followed by histopathology studies were also conducted.

Results

It was observed that particle size (PS) of 177.15 ± 7.85 nm, polydispersity index (PDI) of 0.36 ± 2.55, zeta potential (ZP) of − 21.26 ± 0.19 mV, and entrapment efficiency percentage (EE%) of 72.58 ± 8.82% was obtained with a percent deviation of less than 5. G4 batch consisting of 18% w/v of PF127 demonstrated satisfactory results. Furthermore, the results were in accordance with the phase transition and the formulation displayed a pseudoplastic rheological behavior confirmed by the rheogram. The optimized formulation’s in vitro drug permeation measurements demonstrated 90.69% release after 5 h. The ex vivo permeation also revealed a 2.52 enhancement ratio when compared to plain in situ gel. Histopathology analyses showed a non-toxic effect of the optimized composition on the cellular structure of sheep’s nasal mucosa. A short-term stability analysis revealed that the formulation was stable at room temperature for 3 months.

Conclusion

ALM-loaded intranasal cubosomal in situ gel is likely to promote patient compliance by delivering immediate relief from migraine pain due to its rapid onset of action and safe dosage form.

Graphical Abstract

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新型自组装立方液晶的鼻内纳米递送:配方和评价

目的本研究的重点是开发含有苹果酸阿莫曲坦（ALM）的立方体原位凝胶，以改善其通过血脑屏障（BBB）的渗透性，并在通过鼻内途径给药时高效、快速地发挥作用。方法按照方框-贝肯设计（BBD）的建议，将不同比例和浓度的pluronics F127（PF127）和甘油单油酸酯（GMO）以及聚乙烯醇（PVA）进行乳化和均质，制成立方体。利用可取函数选择最佳立方体配方。高分辨率透射电子显微镜（HR-TEM）分析验证了所开发的立方体形态。差示扫描量热法（DSC）的峰值证明纳米载体系统中含有药物。在配制和优化原位凝胶时，使用了不同浓度的 PF127（15-21% w/v）。结果表明，粒度（PS）为 177.15 ± 7.85 nm，多分散指数（PDI）为 0.36 ± 2.55，Zeta 电位（ZP）为 - 21.26 ± 0.19 mV，夹带效率百分比（EE%）为 72.58 ± 8.82%，百分比偏差小于 5。含有 18% w/v PF127 的 G4 批次结果令人满意。此外，结果与相变相符，流变图证实制剂呈现假塑性流变行为。优化配方的体外药物渗透测量结果表明，5 小时后药物释放率为 90.69%。组织病理学分析表明，优化组合物对绵羊鼻黏膜的细胞结构无毒性影响。结论ALM负载的鼻内立方体原位凝胶由于起效迅速、剂型安全，可以立即缓解偏头痛，从而提高患者的依从性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Pharmaceutical Innovation PHARMACOLOGY & PHARMACY-

CiteScore

3.70

自引率

3.80%

发文量

审稿时长

>12 weeks

期刊介绍： The Journal of Pharmaceutical Innovation (JPI), is an international, multidisciplinary peer-reviewed scientific journal dedicated to publishing high quality papers emphasizing innovative research and applied technologies within the pharmaceutical and biotechnology industries. JPI''s goal is to be the premier communication vehicle for the critical body of knowledge that is needed for scientific evolution and technical innovation, from R&D to market. Topics will fall under the following categories: Materials science, Product design, Process design, optimization, automation and control, Facilities; Information management, Regulatory policy and strategy, Supply chain developments , Education and professional development, Journal of Pharmaceutical Innovation publishes four issues a year.