Inhalable, bioresponsive microparticles for targeted drug delivery in the lungs.
OBJECTIVE: There is a growing interest in developing bioresponsive drug delivery systems to achieve greater control over drug release than can be achieved with the conventional diffusion controlled polymeric delivery systems. While a number of such systems have been studied for oral or parenteral delivery, little or no work has been done on bioresponsive delivery systems for inhalation. Using the raised elastase levels present at sites of lung inflammation as a proof-of-concept model, we endeavoured to develop a prototype of inhalable elastase sensitive microparticles (ESMs).
METHODS: Microparticles degradable by the enzyme elastase were formed by crosslinking the polymer alginate in the presence of an elastase substrate, elastin, using Ca(+2) ions and subsequent spray drying.
KEY FINDINGS: The bioresponsive release of a protein cargo in the presence of elastase demonstrated the enzyme-specific degradability of the particles. The microparticles showed favorable properties such as high drug encapsulation and good powder dispersibility. Potential polymer toxicity in the lungs was assessed by impinging the microparticles on Calu-3 cell monolayers and assessing changes in transepithelial permeability and induction of cytokine release. The microparticles displayed no toxic or immunogenic effects.
CONCLUSIONS: With a manufacturing method that is amenable to scale-up, the ability to be aerosolised efficiently from a first-generation inhaler device, enzyme-specific degradability and lack of toxicity, the ESMs show significant promise as pulmonary drug carriers.
The authors acknowledge Mr. Neal Leddy for assistance with the SEM. This research was supported by the Science Foundation Ireland (Grant 05/RFP/ENG0020).
CommentsThis is the pre-peer reviewed version of the following article: Journal of Pharmacy and Pharmacology. 2011;63(3):369-75, which has been published in final form at doi: 10.1111/j.2042-7158.2010.01234.x. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."
Published CitationSivadas N, Cryan SA. Inhalable, bioresponsive microparticles for targeted drug delivery in the lungs. Journal of Pharmacy and Pharmacology. 2011;63(3):369-75.
- School of Pharmacy and Biomolecular Sciences