In vitro–in vivo correlation of inhalable budesonide-loaded large porous particles for sustained treatment regimen of asthma
| Autor: | Lan Zhang, Uwe Muenster, Yuyang Zhang, Jiaqi Li, Lu Qin, Linc Chen, Linglong Yang, Huangliang Zheng, Shirui Mao, Linlin Fan, Xiaofei Zhang, En-Yu Xu, Moritz Beck-Broichsitter |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Drug Budesonide media_common.quotation_subject 0206 medical engineering Biomedical Engineering 02 engineering and technology Pharmacology Biochemistry Rats Sprague-Dawley Biomaterials Mice chemistry.chemical_compound Drug Delivery Systems IVIVC Pharmacokinetics In vivo medicine Animals Molecular Biology media_common Chemistry General Medicine 021001 nanoscience & nanotechnology 020601 biomedical engineering Asthma Rats PLGA RAW 264.7 Cells Pharmacodynamics Drug delivery 0210 nano-technology Porosity Biotechnology medicine.drug |
| Zdroj: | Acta Biomaterialia. 96:505-516 |
| ISSN: | 1742-7061 |
| DOI: | 10.1016/j.actbio.2019.06.056 |
| Popis: | Large porous particles (LPPs) are well-known vehicles for drug delivery to the lungs. However, it remains uncertain whether or to which extent the in vitro drug release behavior of LPPs can be predictive of their in vivo performance (e.g., systemic exposure and therapeutic efficacy). With regard to this, three budesonide-loaded LPP formulations with identical composition but distinct in vitro drug release profiles were studied in vivo for their pharmacokinetic and pharmacodynamic behavior after delivery to rat lung, and finally, an in vitro/in vivo correlation (IVIVC) was established. All formulations reduced approximately 75% of the uptake by RAW264.7 macrophages compared with budesonide/lactose physical mixture and showed a drug release-dependent retention behavior in the lungs of rats. Likewise, the highest budesonide plasma concentration was measured for the formulation revealing the fastest in vitro drug release. After deconvolution of the plasma concentration/time profiles, the calculated in vivo drug release data were successfully utilized for a point-to-point IVIVC with the in vitro release profiles and the predictability of the developed IVIVC was acceptable. Finally, effective therapy was observed in an allergic asthma rat model for the sustained drug release formulations. Overall, the obtained in vitro results correlate well with the systemic drug exposure and the therapeutic performance of the investigated lung-delivered formulations, which can provide an experimental basis for IVIVC development in the pulmonary-controlled delivery system. STATEMENT OF SIGNIFICANCE: Large porous particles (LPPs) are well-known vehicles for drug delivery to the lungs. However, it remains uncertain whether or to which extent the in vitro drug release behavior of LPPs can be predicted by their in vivo performance (e.g., systemic exposure and therapeutic efficacy). With regard to this, three budesonide-loaded PLGA-based LPP formulations with identical composition but distinct in vitro drug release profiles were studied in vivo for their pharmacokinetic and pharmacodynamic behavior, and finally, an in vitro/in vivo correlation (IVIVC) was established. It was demonstrated that the influence of the in vitro drug release profile was obvious during lung retention, systemic exposure, and therapeutic efficacy measurements. An IVIVC (Level A) was successfully established for the budesonide-loaded LPPs delivered to the airspace of rats for the first time. Taken together, the present work will clearly support research and development activities in the field of controlled drug delivery to the lungs. |
| Databáze: | OpenAIRE |
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