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质量源于设计驱动的载地塞米松壳聚糖微球的靶向肺部给药:生物分布和药代动力学研究。

QbD driven targeted pulmonary delivery of dexamethasone-loaded chitosan microspheres: Biodistribution and pharmacokinetic study.

作者信息

Asha B R, Goudanavar Prakash, Koteswara Rao G S N, Gandla Kumaraswamy, Raghavendra Naveen N, Majeed Shahnaz, Muthukumarasamy Ravindran

机构信息

Department of Pharmaceutics, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, B.G. Nagar, Karnataka 571448, India.

Department of Pharmaceutics, Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's NMIMS, Vile Parle (W), Mumbai 400056, Maharashtra, India.

出版信息

Saudi Pharm J. 2023 Sep;31(9):101711. doi: 10.1016/j.jsps.2023.101711. Epub 2023 Jul 26.

DOI:10.1016/j.jsps.2023.101711
PMID:37564747
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10410579/
Abstract

Inhaling drugs, on the other hand, is limited mainly by the natural mechanisms of the respiratory system, which push drug particles out of the lungs or make them inefficient once they are there. Because of this, many ways have been found to work around the problems with drug transport through the lungs. Researchers have made polymeric microparticles (MP) and nanoparticles as a possible way to get drugs into the lungs. They showed that the drug could be trapped in large amounts and retained in the lungs for a long time, with as little contact as possible with the bloodstream. MP were formulated in this study to get dexamethasone (DMC) into the pulmonary area. The Box-Behnken design optimized microspheres preparation to meet the pulmonary delivery prerequisites. Optimized formulation was figured out based on the desirability approach. The mass median aerodynamic diameter (MMAD) of the optimized formula (O-DMC-MP) was 8.46 ± 1.45 µm, and the fine particle fraction (FPF) was 77.69 ± 1.26%. This showed that it made suitable drug delivery system, which could make it possible for MP to settle deeply in the lung space after being breathed in. With the first burst of drug release, it was seen that drug release could last up to 16 h. Also, there was no clear sign that the optimized formulation was toxic to the alveoli basal epithelial cells in the lungs, as supported by cytotoxic studies in HUVEC, A549, and H1299 cell lines. Most importantly, loading DMC inside MP cuts the amount of drug into the bloodstream compared to plain DMC, as evident from biodistribution studies. Stability tests have shown that the product can stay the same over time at both the storage conditions. Using chitosan DMC-MP can be a better therapeutic formulation to treat acute respiratory distress syndrome (ARDS).

摘要

另一方面,吸入药物主要受到呼吸系统自然机制的限制,这些机制会将药物颗粒排出肺部,或者使药物颗粒一旦进入肺部就变得低效。因此,人们已经找到了许多方法来解决药物通过肺部运输的问题。研究人员制备了聚合物微粒(MP)和纳米颗粒,作为将药物输送到肺部的一种可能途径。他们表明,药物可以大量捕获并长时间保留在肺部,与血液的接触尽可能少。本研究中制备MP是为了将地塞米松(DMC)输送到肺部区域。采用Box-Behnken设计优化微球制备,以满足肺部给药的前提条件。基于期望函数法确定了优化配方。优化配方(O-DMC-MP)的质量中值空气动力学直径(MMAD)为8.46±1.45μm,细颗粒分数(FPF)为77.69±1.26%。这表明它制成了合适的药物递送系统,使得MP在吸入后能够深入沉积在肺间隙中。随着药物的首次突释,可见药物释放可持续长达16小时。此外,在人脐静脉内皮细胞(HUVEC)、A549和H1299细胞系中的细胞毒性研究表明,没有明显迹象表明优化配方对肺部肺泡基底上皮细胞有毒性。最重要的是,与普通DMC相比,将DMC负载在MP中可减少进入血液的药量,生物分布研究表明了这一点。稳定性测试表明,该产品在两种储存条件下都能随时间保持不变。使用壳聚糖DMC-MP可能是治疗急性呼吸窘迫综合征(ARDS)的更好治疗制剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9ea/10410579/bbb3bdbf8f10/gr9.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9ea/10410579/82b424ed9636/gr4.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9ea/10410579/ec0925347ade/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9ea/10410579/3bcbe4ba4ea5/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9ea/10410579/875700763202/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9ea/10410579/bbb3bdbf8f10/gr9.jpg

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