Peer Reviewed

1

Document Type

Article

Publication Date

1-3-2011

Keywords

Administration, Inhalation, Adult, Aerosols, Alginates, Cell Membrane Permeability, Cells, Cultured, Drug Delivery Systems, Elastin, Fluorescein-5-isothiocyanate, Glucuronic Acid, Hematoporphyrins, Hexuronic Acids, Humans, Leukocyte Elastase, Lung, Male, Microspheres, Models, Biological, Particle Size, Serum Albumin, Bovine, Tumor Cells, Cultured

Funder/Sponsor

The authors acknowledge Mr. Neal Leddy for assistance with the SEM. This research was supported by the Science Foundation Ireland (Grant 05/RFP/ENG0020).

Comments

This 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."

Abstract

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.

Disciplines

Pharmacy and Pharmaceutical Sciences

Citation

Sivadas N, Cryan SA. Inhalable, bioresponsive microparticles for targeted drug delivery in the lungs. Journal of Pharmacy and Pharmacology. 2011;63(3):369-75.

PubMed ID

21749384

DOI Link

10.1111/j.2042-7158.2010.01234.x

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.

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