Shedding Light on the Trehalose‐Enabled Mucopermeation of Nanoparticles with Label‐Free Raman Spectroscopy. Issue 33 (3rd July 2019)

• Record Type: Journal Article
• Authors: Siddhanta, Soumik; Bhattacharjee, Sourav; Harrison, Sabine M.; Scholz, Dimitri; Barman, Ishan
• Is Part Of: Small. Volume 15:Issue 33(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-07-03
• Subjects: drug delivery -- porcine jejunal mucus -- Raman spectroscopy -- SERS -- trehalose; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.201901679
• Languages: English
• ISSNs: 1613-6810

Abstract

Abstract: Nanoparticle‐based drug delivery systems have attracted significant interest owing to their promise as tunable platforms that offer improved intracellular release of cargo therapeutics. However, significant challenges remain in maintaining the physiological stability of the mucosal matrix due to the nanoparticle‐induced reduction in the matrix diffusivity and promotion of mucin aggregation. Such aggregation also adversely impacts the permeability of the nanoparticles, and thus, diminishes the efficacy of nanoparticle‐based formulations. Here, an entirely complementary approach is proposed to the existing nanoparticle functionalization methods to address these challenges by using trehalose, a naturally occurring disaccharide that offers exceptional protein stabilization. Plasmon‐enhanced Raman spectroscopy and far‐red fluorescence emission of the plasmonic silver nanoparticulate clusters are harnessed to create a unique dual‐functional, aggregating, and imaging agent that obviates the need of an additional reporter to investigate mucus–nanoparticle interactions. These spectroscopy‐based density mapping tools uncover the mechanism of mucus–nanoparticle interactions and establish the protective role of trehalose microenvironment in minimizing the nanoparticle aggregation. Thus, in contrast to the prevailing belief, these results demonstrate that nonfunctionalized nanoparticles may rapidly penetrate through mucus barriers, and by leveraging the bioprotectant attributes of trehalose, an in vivo milieu for efficient mucosal drug delivery can be generated. Abstract : Overcoming the mucosal barrier has been a challenge for several nanotherapeutic agents. This study reports a trehalose‐mediated method for enhanced mucopermeation of nanoparticles, which can be harnessed for drug‐delivery and label‐free imaging applications.