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一种由包裹硫酸庆大霉素的聚乳酸-羟基乙酸共聚物（PLGA）大孔颗粒组成的干粉吸入器的制备与表征

Preparation and Characterization of a Dry Powder Inhaler Composed of PLGA Large Porous Particles Encapsulating Gentamicin Sulfate.

作者信息

Shiehzadeh Farideh, Tafaghodi Mohsen, Dehghani Majid-Laal, Mashhoori Faezeh, Fazly Bazzaz Bibi Sedigheh, Imenshahidi Mohsen

机构信息

School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Adv Pharm Bull. 2019 Jun;9(2):255-261. doi: 10.15171/apb.2019.029. Epub 2019 Jun 1.

DOI:10.15171/apb.2019.029
PMID:31380251
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6664120/
Abstract

Direct delivery of aminoglycosides to the lungs was under extensive evaluations during the last decades. Because of large particle size, low density and porous structure, large porous particles (LPPs) are versatile carriers for this purpose. In this study, poly (lactic-co-glycolic acid) (PLGA) LPPs encapsulating gentamicin sulfate were prepared and characteristics of their freeze-dried powder as a dry powder inhaler (DPI) were evaluated. To prepare PLGA LPPs, a double emulsification-solvent evaporation method was optimized and gentamicin sulfate was post-loaded in the LPPs. characteristics including morphological features, thermal behavior, aerodynamic profile and cumulative drug release were evaluated by the scanning electron microscope (SEM), differential scanning calorimetry (DSC), next-generation cascade impactor (NGI) and Franz diffusion cell respectively. The obtained results revealed that the preparation method was capable to produce spherical large homogenous highly porous particles. 94% of gentamicin sulfate released from LPPs up to 30 minutes. Mass median aerodynamic diameter (MMAD) and fine particle fraction (FPF) were 4.9 µm and 39% respectively. In this study, dry powder formulation composed of PLGA LPPs encapsulating gentamicin sulfate showed a promising behavior as a pulmonary delivery carrier. Improvements on the aerodynamic behavior and evaluations recommended for further developments.

摘要

在过去几十年中，氨基糖苷类药物向肺部的直接递送受到了广泛评估。由于粒径大、密度低和多孔结构，大孔颗粒（LPPs）是用于此目的的通用载体。在本研究中，制备了包裹硫酸庆大霉素的聚（乳酸-乙醇酸）（PLGA）LPPs，并评估了其作为干粉吸入器（DPI）的冻干粉末的特性。为了制备PLGA LPPs，优化了双乳化-溶剂蒸发法，并将硫酸庆大霉素后载入LPPs中。分别通过扫描电子显微镜（SEM）、差示扫描量热法（DSC）、下一代撞击器（NGI）和Franz扩散池评估了包括形态特征、热行为、空气动力学分布和药物累积释放等特性。所得结果表明，该制备方法能够制备出球形、均匀、高度多孔的大颗粒。硫酸庆大霉素从LPPs中在30分钟内释放了94%。质量中值空气动力学直径（MMAD）和细颗粒分数（FPF）分别为4.9 µm和39%。在本研究中，由包裹硫酸庆大霉素的PLGA LPPs组成的干粉制剂作为肺部递送载体表现出了良好的性能。建议对空气动力学行为进行改进并进行进一步的评估以推动其发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa80/6664120/17688e32b1f5/apb-9-255-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa80/6664120/29bfa4338abb/apb-9-255-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa80/6664120/9fc67bacb258/apb-9-255-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa80/6664120/e4f3444b942f/apb-9-255-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa80/6664120/75a46de4fba3/apb-9-255-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa80/6664120/17688e32b1f5/apb-9-255-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa80/6664120/29bfa4338abb/apb-9-255-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa80/6664120/9fc67bacb258/apb-9-255-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa80/6664120/e4f3444b942f/apb-9-255-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa80/6664120/75a46de4fba3/apb-9-255-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa80/6664120/17688e32b1f5/apb-9-255-g005.jpg

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本文引用的文献

[1]
Ethambutol-Loaded Solid Lipid Nanoparticles as Dry Powder Inhalable Formulation for Tuberculosis Therapy.

AAPS PharmSciTech. 2019-2-22

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Pharm Res. 2018-8-23

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Expert Opin Drug Deliv. 2018-7-26

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Drug Dev Ind Pharm. 2017-8

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Int J Pharm. 2012-1-23

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Biomaterials. 2010-12-3

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