Journal
ACS NANO
Volume 9, Issue 8, Pages 8291-8302Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.5b02762
Keywords
chitosan; dual-delivery; microfluidics; PLGA; porous silicon
Categories
Funding
- European Regional Development Fund (ERDF) through the Programa Operacional Factores de Competitividade - COMPETE
- Fundacao para a Ciencia e a Tecnologia (FCT) [PEst-C/SAU/LA0002/2013]
- North Portugal Regional Operational Programme (ON.2 - O Novo Norte) in the framework of project SAESCTN-PIIC&DT under the National Strategic Reference Framework (NSRF)
- FCT [SFRH/BD/87016/2012]
- Academy of Finland [252215, 281300]
- University of Helsinki
- Biocetrum Helsinki
- Finnish Center for International Mobility [TM-13-9048]
- European Research Council under the European Union [310892]
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Multifunctional tailorable composite systems, specifically designed for oral dual-delivery of a peptide (glucagon-like peptide-1) and an enzymatic inhibitor (dipeptidyl peptidase 4 (DPP4)), were assembled through the microfluidics technique. Both drugs were coloaded into these systems for a synergistic therapeutic effect. The systems were composed of chitosan and cell-penetrating peptide modified poly(lactide-co-glycolide) and porous silicon nanoparticles as nanomatrices, further encapsulated in an enteric hydroxypropylmethylcellulose acetylsuccinate polymer. The developed multifunctional systems were pH-sensitive, inherited by the enteric polymer, enabling the release of the nanoparticles only in the simulated intestinal conditions. Moreover, the encapsulation into this polymer prevented the degradation of the nanoparticles' modifications. These nanoparticles showed strong and higher interactions with the intestinal cells in comparison with the nonmodified ones. The presence of DPP4 inhibitor enhanced the peptide permeability across intestinal cell monolayers. Overall, this is a promising platform for simultaneously delivering two drugs from a single formulation. Through this approach peptides are expected to increase their bioavailability and efficiency in vivo both by their specific release at the intestinal level and also by the reduced enzymatic activity. The use of this platform, specifically in combination of the two antidiabetic drugs, has clinical potential for the therapy of type 2 diabetes mellitus.
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