Inhalable PLGA microspheres: Tunable lung retention and systemic exposure via polyethylene glycol modification
| Autor: | Michael Moehwald, En-Yu Xu, Shirui Mao, Linc Chen, Jiaqi Li, Huangliang Zheng, Xin Zhang |
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| Rok vydání: | 2020 |
| Předmět: |
Molar
0206 medical engineering Biomedical Engineering macromolecular substances 02 engineering and technology Polyethylene glycol Pharmacology Biochemistry Polyethylene Glycols Biomaterials chemistry.chemical_compound In vivo PEG ratio medicine Animals Molecular Biology Lung Chemistry technology industry and agriculture General Medicine 021001 nanoscience & nanotechnology 020601 biomedical engineering Mucus Microspheres Rats PLGA Drug Liberation medicine.anatomical_structure Alveolar macrophage Nanoparticles 0210 nano-technology Biotechnology |
| Zdroj: | Acta biomaterialia. 123 |
| ISSN: | 1878-7568 |
| Popis: | Polyethylene glycol (PEG) modification is one of the promising approaches to overcome both mucus and alveolar macrophage uptake barriers in the deep lung for sustained therapy of pulmonary diseases such as asthma. To investigate the feasibility of using PEG-modified microspheres to bypass both barriers, we prepared a collection of polyethylene glycol-distearoyl glycero-phosphoethanolamine (PEG-DSPE)-modified poly (lactide-co-glycolide) (PLGA) microspheres bearing specific PEG molecular weights (0.75, 2, 5, and 10 kDa) and PEG-DSPE/PLGA molar ratios (0.25:1 and 1:1). Drug release, mucus penetration, and macrophage uptake were evaluated in vitro, and the corresponding in vivo activities of microspheres in rats were investigated. It was found that the PEG2000-DSPE/PLGA 1:1 group showed enhanced mucus permeability and reduced macrophage uptake in vitro compared to the PEG2000-DSPE/PLGA 0.25:1 group. At high PEG molar ratios, only the PEG 2000-based group showed significantly prolonged lung retention in vivo compared to the control group. The systemic exposure of the PEG2000-DSPE/PLGA 1:1 group was significantly lower than that of the PEG2000-DSPE/PLGA 0.25:1 group (39% of AUC reduction). Additionally, when using the same molar ratio of 1:1, the PEG 2000 group significantly lowered the systemic drug exposure compared to that of the PEG 5000 and 10000 groups (48% and 33% of AUC reduction, respectively), thus making it a promising sustained lung delivery candidate for pulmonary disease treatment. |
| Databáze: | OpenAIRE |
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