Journal
ARCHIVES OF PHARMACAL RESEARCH
Volume 41, Issue 8, Pages 848-860Publisher
PHARMACEUTICAL SOC KOREA
DOI: 10.1007/s12272-018-1062-y
Keywords
Oral delivery; Microparticles; Macropore; Digestive tract; pH
Categories
Funding
- Bill AMP
- Melinda Gates Foundation [OPP1061366]
- Alberta Innovates Technology Futures [AIF200900279]
- University of Alberta
- Bill and Melinda Gates Foundation [OPP1061366] Funding Source: Bill and Melinda Gates Foundation
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Microparticles (MPs) have been extensively researched as a potential drug delivery vehicle. Here, we investigated the fabrication of MPs with pH-responsive macropores and evaluated their potential applicability in developing solid oral drug formulations. Our previous study showed that macropored MPs, made of Eudragit(A (R)) L100-55, could encapsulate 100 nm, 1 A mu m, and 4 A mu m sized fluorescent beads-model drugs that are mimicking vaccines, bacteria, and cells. In the present study, closed-pored MPs after freeze-drying were coated with a gastric soluble Eudragit(A (R)) EPO layer to protect MPs in the simulated pregastric environment. Subsequently, drug encapsulated MPs maintained their intact closed-pored structure in the simulated gastric environment and exhibited a rapid release in the simulated intestine environment. Our MP system was found to provide a significantly higher level of protection to the encapsulated lactase enzyme compared to the control sample (i.e. without using MPs). Real-time fluorescence microscopy analysis showed that macropored MPs released encapsulated drugs in a burst-release pattern and in a size-independent manner. This work shows that our proposed EPO-coated MPs with pH-responsive macropores can meet the challenges posed by the multiple physiological environments of the digestive tract and be used in developing highly effective solid oral drug/vaccine formulations.
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