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Lactoferrin-conjugated pH and redox-sensitive polymersomes based on PEG-S-S-PLA-PCL-OH boost delivery of bacosides to the brain

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Abstract

In the present study, engineered lactoferrin (Lf)-conjugated pH and redox-sensitive polymersomes derived from the triblock copolymer polyethylene glycol-S-S-polylactic acid-polycaprolactone (PEG-S-S-PLA-PCL-OH) have been used to deliver bacosides to the brain. Bacosides are classified as triterpenoid saponins and are used in Indian Ayurveda for reversal of amnesia; however, no study has extensively demonstrated their efficacy as a nano-formulation in an animal model. The polymer was synthesized by ring opening polymerization of lactide and ε-caprolactone. The nanoparticles obtained by nanoprecipitation showed a core–shell morphology, with an average size of 110 nm, by transmission electron microscopy (TEM). The colloidal stability, hemocompatibility and cytocompatibility of the polymersomes proved their biocompatibility. pH and disulfide linkages in the polymeric chain accelerated the disintegration of the polymersomes at pH 6.6 and at pH 6.6 with glutathione (GSH) in comparison to pH 7.4, supporting their degradation behavior. Supermagnetic iron oxide nanoparticles (SPIONs, 74.99 μg mg−1 polymer) encapsulated into the polymersomes demonstrated their uptake in a mouse model by MRI. Furthermore, bacosides encapsulated in the polymersomes (10% loading) showed significant memory loss reversal in chemically induced amnesic mice, supported by the gene expression profiles of Arc, BDNF and CREB as well as by histopathology.

Graphical abstract: Lactoferrin-conjugated pH and redox-sensitive polymersomes based on PEG-S-S-PLA-PCL-OH boost delivery of bacosides to the brain

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Publication details

The article was received on 11 May 2018, accepted on 24 Aug 2018 and first published on 31 Aug 2018


Article type: Paper
DOI: 10.1039/C8NR03828G
Citation: Nanoscale, 2018, Advance Article
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    Lactoferrin-conjugated pH and redox-sensitive polymersomes based on PEG-S-S-PLA-PCL-OH boost delivery of bacosides to the brain

    K. Goyal, A. Konar, B. S. H. Kumar and V. Koul, Nanoscale, 2018, Advance Article , DOI: 10.1039/C8NR03828G

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