Abstract
Nanomaterials are emerging as strong candidates for applications in drug delivery and offer an alternative platform to modulate the differentiation and activity of neural stem cells. Herein we report the synthesis and characterization of two different classes of polymeric nanoparticles: N-isopropylacrylamide-based thermoresponsive nanogels RM1 and P(TEGA)-b-P(d,lLA)2 nano-micelles RM2. We covalently linked the nanoparticles with fluorescent tags and demonstrate their ability to be internalized and tracked in neural stem cells from the postnatal subventricular zone, without affecting their proliferation, multipotency and differentiation characteristics up to 150 μg ml-1. The difference in chemical structure of RM1 and RM2 does not appear to impact toxicity however it influences the loading capacity. Nanogels RM1 loaded with retinoic acid improve solubility of the drug which is released at 37 °C, resulting in an increase in the number of neurons, comparable to what can be obtained with a solution of the free drug solubilised with a small percentage of DMSO.
Highlights
Ageing, neurodegenerative diseases and neurovascular disorders are increasingly common conditions associated with major irreversible loss of neurons and glial cells, resulting in high mortality and high health care costs.[1]
Fluorescent moieties are commonly encapsulated into a polymer matrix and used for such applications, the stability in vitro of these system is a cause for concern, with the tags often becoming separated from the matrix
In this study we demonstrate that NIPAM nanogels and P(TEGA)-b-P(D,LLA)[2] based micelles are taken up and internalized in the cytoplasm of the subventricular zone (SVZ) neural stem cells, without having any significant impact on their proliferation, differentiation and self-renewal properties
Summary
Neurodegenerative diseases and neurovascular disorders are increasingly common conditions associated with major irreversible loss of neurons and glial cells, resulting in high mortality and high health care costs.[1]. A number of promising strategies, designed to achieve brain protection, repair and recovery, have been investigated, such as delivery of neuroprotective compounds to prevent cellular degeneration,[2] use of tissue engineering, cell replacement and cell transplantation.[3] sustained bioavailability and poor cell survival and integration in the host have considerably limited the applications. A more recent and attractive approach has focused on targeting endogenous neural stem cells (NSC), an important reservoir of self-renewing and multipotent cells that can drive regeneration and repair, conferring a certain degree of plasticity to the adult brain.[2] The subventricular zone (SVZ) of the lateral ventricle and the subgranular zone of the dentate
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