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Development of highly porous large PLGA microparticles for pulmonary drug delivery

Paper ID Volume ID Publish Year Pages File Format Full-Text
10603 693 1953 7 PDF Available
Title
Development of highly porous large PLGA microparticles for pulmonary drug delivery
Abstract

We report a new process of making highly-porous large polymeric microparticles for local drug delivery to the lungs by inhalation. Poly(lactic-co-glycolic acid) (PLGA) microparticles (average diameter, 10–20 μm) were made by the double-emulsion method. To impart favorable aerodynamic properties, an effervescent salt ammonium bicarbonate (ABC) was included in the internal aqueous phase. ABC produced highly-porous structures in the PLGA particles as it escaped as ammonia and carbon dioxide. The fine-particle fraction (FPF) of the microparticles increased as a function of the ratio of ABC to PLGA. Microparticles prepared with 7.5%w/w (ABC/PLGA) had a mass median aerodynamic diameter (MMAD) of 4.0 ± 1.2 μm and FPF of 32.0 ± 9.1% when tested with Anderson Cascade Impactor (ACI) and Rotahaler. The highly-porous large particles deposited at the ACI stages corresponding to the trachea and below. The highly-porous large particles avoided phagocytosis by macrophages, while non-porous small particles were quickly taken up by the macrophages. Unlike other encapsulation methods which employ osmogens or extractable porogens, this method could encapsulate lysozyme and doxorubicin·HCl, with high encapsulation efficiency (∼100% for both lysozyme and doxorubicin), in the PLGA microparticles characterized by desirable MMAD (4.5 ± 0.6 μm lysozyme; 4.6 ± 0.4 μm doxorubicin) and FPF (29.1 ± 12.2% lysozyme; 33.8 ± 3.6% doxorubicin). Fifty-two percent of encapsulated doxorubicin was released over 4 days from the highly-porous microparticles. This method is an efficient way of making polymeric microparticles for sustained local drug delivery by inhalation.

Keywords
Highly porous large microparticles; Ammonium bicarbonate; Inhalable dry powder; Inhalational therapy; Sustained drug delivery
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Development of highly porous large PLGA microparticles for pulmonary drug delivery
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 30, Issue 10, April 2009, Pages 1947–1953
Authors
, , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us