Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 525, Issue 1, Pages 264-274Publisher
ELSEVIER
DOI: 10.1016/j.ijpharm.2017.04.052
Keywords
Acetalated dextran; Nanocomposite microparticles; Microparticles; Pulmonary delivery; Spray drying; Controlled release
Categories
Funding
- Institutional Development Award (IDeA) from National Institute of General Medical Sciences of the National Institutes of Health [P20GM103430]
- National Science Foundation EPSCoR [EPS-1004057]
- National Science Foundation [1508868]
- Div Of Chem, Bioeng, Env, & Transp Sys
- Directorate For Engineering [1508868] Funding Source: National Science Foundation
- Office of Integrative Activities
- Office Of The Director [1004057] Funding Source: National Science Foundation
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Biocompatible, biodegradable polymers are commonly used as excipients to improve the drug delivery properties of aerosol formulations, in which acetalated dextran (Ac-Dex) exhibits promising potential as a polymer in various therapeutic applications. Despite this promise, there is no comprehensive study on the use of Ac-Dex as an excipient for dry powder aerosol formulations. In this study, we developed and characterized pulmonary drug delivery aerosol microparticle systems based on spray-dried Ac-Dex with capabilities of (1) delivering therapeutics to the deep lung, (2) targeting the particles to a desired location within the lungs, and (3) releasing the therapeutics in a controlled fashion. Two types of Ac-Dex, with either rapid or slow degradation rates, were synthesized. Nanocomposite microparticle (nCmP) and microparticle (MP) systems were successfully formulated using both kinds of Ac-Dex as excipients and curcumin as a model drug. The resulting MP were collapsed spheres approximately 1 mm in diameter, while the nCmP were similar in size with wrinkled surfaces, and these systems dissociated into 200 nm nanoparticles upon reconstitution in water. The drug release rates of the Ac-Dex particles were tuned by modifying the particle size and ratio of fast to slow degrading Ac-Dex. The pH of the environment was also a significant factor that influenced the drug release rate. All nCmP and MP systems exhibited desirable aerodynamic diameters that are suitable for deep lung delivery (e.g. below 5 mu m). Overall, the engineered Ac-Dex aerosol particle systems have the potential to provide targeted and effective delivery of therapeutics into the deep lung. (C) 2017 Elsevier B.V. All rights reserved.
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