Novel Nanoaggregates from Phoenix dactylifera (date palm) for Inhalational Management of Cystic Fibrosis Using Dry Powder Inhalers

IF 2.7 4区医学 Q2 PHARMACOLOGY & PHARMACY Journal of Pharmaceutical Innovation Pub Date : 2023-07-14 DOI:10.1007/s12247-023-09752-3

Hadeel Aburass, Nisreen Dahshan, Hamad Alyami, Affiong Iyire, Eman Zmaily Dahmash

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Abstract

Purpose

Phoenix dactylifera extracts have shown efficacy as antioxidants and antibacterials for the treatment of lung diseases; however, the choice of route of administration remains a problem. The use of natural antibacterial remedies for the management of cystic fibrosis (CF) is promising due to recurring bacterial resistance to current antibiotics. Dry powder inhalers (DPIs) have also been identified as a patient-friendly, noninvasive method for local delivery of drugs to the lungs. Therefore, this work, which is the first of its kind, aimed to formulate nanoparticles of date palm extracts as DPIs and evaluate their aerodynamic and antibacterial biofilm characteristics for the potential treatment of CF.

Method

Chitosan-based nanoparticles (CDN) comprising aqueous date fruit extract with increasing concentrations of chitosan (0.05, 0.1, and 0.2% w/v) were prepared. The in vitro aerosolization of the formulations was studied using a next-generation impactor (NGI), and good aerosolization profiles were achieved. The produced nanoparticles were characterized using FTIR and XRD to confirm physical properties and TEM and zeta sizer to confirm shape and size. The antimicrobial activity of CDN was evaluated using a Pseudomonas aeruginosa biofilm model cultured in an artificial sputum medium (ASM) mimicking cystic fibrosis conditions in the lungs.

Results

Nanoparticles containing 0.05% w/v chitosan demonstrated the highest encapsulation efficiency (55.91%) and delivered the highest emitted dose (98.92%) and fine particle fraction (42.62%). CDN demonstrated the first-time-ever reported significant 3.3 log-cycle inhibition of P. aeruginosa biofilm cultured in ASM. TEM images revealed the formation of spherical particles with an average size of 42.98 ± 19.19 nm. FTIR and XRD studies demonstrated the compatibility of the components with the presence of the characteristic features of chitosan and date powder.

Conclusions

This novel work showcases CDN as a prophylactic adjuvant for the management of cystic fibrosis using DPI.

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用干粉吸入器吸入治疗囊性纤维化的新型指掌纳米聚集体

目的凤仙花提取物作为抗氧化剂和抗菌剂具有治疗肺部疾病的功效，但给药途径的选择仍是一个问题。由于细菌对现有抗生素的耐药性反复出现，使用天然抗菌药治疗囊性纤维化（CF）前景广阔。干粉吸入器（DPI）也被认为是一种方便患者、无创的肺部局部给药方法。因此，本研究首次将枣树提取物配制成纳米颗粒作为干粉吸入器，并评估其空气动力学特性和抗菌生物膜特性，以用于潜在的 CF 治疗。方法制备了壳聚糖基纳米颗粒（CDN），其中包括水性枣果提取物和浓度不断增加的壳聚糖（0.05%、0.1% 和 0.2% w/v）。使用新一代冲击器（NGI）对制剂的体外气溶胶化进行了研究，结果显示气溶胶化效果良好。利用傅立叶变换红外光谱（FTIR）和 X 射线衍射仪（XRD）对制备的纳米粒子进行了物理性质表征，并利用 TEM 和 zeta 分析仪对其形状和尺寸进行了表征。结果含有 0.05% w/v 壳聚糖的纳米颗粒显示出最高的封装效率（55.91%），并提供了最高的发射剂量（98.92%）和细颗粒分数（42.62%）。CDN 对在 ASM 中培养的铜绿假单胞菌生物膜有 3.3 个对数周期的显著抑制作用，这在历史上尚属首次。TEM 图像显示形成了平均尺寸为 42.98 ± 19.19 nm 的球形颗粒。傅立叶变换红外光谱（FTIR）和X射线衍射（XRD）研究表明，这些成分具有相容性，壳聚糖和红枣粉具有特征性特性。

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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.