Engineering butylglyceryl-modified polysaccharides towards nanomedicines for brain drug delivery

Bostanudin, Mohammad F. and Lalatsa, Aikaterini and Górecki, Dariusz C. and Barbu, Eugen (2020) Engineering butylglyceryl-modified polysaccharides towards nanomedicines for brain drug delivery. Carbohydrate Polymers, 236. 116060. ISSN 0144-8617 (https://doi.org/10.1016/j.carbpol.2020.116060)

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Abstract

Colloidal systems prepared from carbohydrates are subject of intense research due to their potential to enhance drug permeability through biological membranes, however their characteristics and performance are never compared directly. Here we report the results of a comparative investigation of a series of butylglyceryl-modified polysaccharides (chitosan, guar gum, and pullulan) that were formulated into nanoparticles and loaded with a range of model actives (Doxorubicin, Rhodamine B, Angiotensin II). Butylglyceryl-modified guar gum and corresponding pullulan nanocarriers were more stable at physiological pH compared to those obtained from modified chitosan, and studies of the in-vitro interactions with mouse brain endothelial cells (bEnd3) indicated an increased biological membrane permeability and lack of toxicity at application-relevant concentrations. No significant haemolytic effect was observed, and confocal microscopy and flow cytometry studies confirmed the efficient cellular uptake and cytoplasmic localisation of NPs. Most promising characteristics for brain drug delivery applications were demonstrated by butylglyceryl pullulan nanocarriers.