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Enzyme-functionalized PLGA nanoparticles with enhanced mucus permeation rate

Enzyme-functionalized PLGA nanoparticles with enhanced mucus permeation rate

Samaridou, Eleni, Karidi, Konstantina, de Sousa, Irene Pereira, Cattoz, Beatrice, Griffiths, Peter, Kammona, Olga, Bernkop-Schnürch, Andreas and Kiparissides, Costas (2014) Enzyme-functionalized PLGA nanoparticles with enhanced mucus permeation rate. Nano LIFE, 4 (4):144101. pp. 1-11. ISSN 1793-9844 (Print), 1793-9852 (Online) (doi:10.1142/S179398441441013X)

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Abstract

The surface functionalization of poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) with various proteolytic enzymes (i.e., trypsin, papain, bromelain) via a two-step carbodiimide coupling method is presented. Depending on the initial Enzyme:NPs ratio, enzyme loadings up to 4.0 wt.%, 4.4 wt.% and 5.34 wt.% were achieved for trypsin, papain and bromelain, respectively. All three conjugated enzymes partially maintained their enzymatic activity after their coupling reaction with the NPs. NPs functionalized with papain and bromelain exhibited a three-fold higher permeability in porcine intestinal mucus compared to nonfunctionalized NPs whereas those conjugated with trypsin showed an almost two-fold higher permeability value. Measurements of the diffusion rates of intestinal mucin, using a nuclear magnetic resonance (NMR) technique, further confirmed these observations, as the enzyme-functionalized NPs were proven to be capable of disrupting the mucin gel structure. According to the reported results, the coupling of proteolytic enzymes to the PLGA NPs' surface largely increases the NPs mucus permeability, thus making it a potentially important mucus permeation strategy.

Item Type: Article
Additional Information: [1] Acknowledgments (funding): The present research has been financially supported by EU under the Seventh Framework Programme [FP7/2007-2013] and the collaborative research project "ALEXANDER" (grant agreement no. NMP-2011-1.2-2-280761).
Uncontrolled Keywords: Poly(DL-lactide-co-glycolide) nanoparticles, enzyme functionalization, mucus gel permeation, oral delivery systems
Subjects: R Medicine > RS Pharmacy and materia medica
Faculty / Department / Research Group: Faculty of Engineering & Science
Faculty of Engineering & Science > Department of Pharmaceutical, Chemical & Environmental Sciences
Related URLs:
Last Modified: 17 Oct 2016 09:13
Selected for GREAT 2016: None
Selected for GREAT 2017: None
Selected for GREAT 2018: None
URI: http://gala.gre.ac.uk/id/eprint/12522

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