<p>Nanocarriers for Stroke Therapy: Advances and Obstacles in Translating Animal Studies</p>

Abstract

The technology of drug delivery systems (DDS) has expanded into many applications, such as for treating neurological disorders. Nanoparticle DDS offer a unique strategy for targeted transport and improved outcomes of therapeutics. Stroke is likely to benefit from the emergence of this technology though clinical breakthroughs are yet to manifest. This review explores the recent advances in this field and provides insight on the trends, prospects and challenges of translating this technology to clinical application. Carriers of diverse material compositions are presented, with special focus on the surface properties and emphasis on the similarities and inconsistencies among in vivo experimental paradigms. Research attention is scattered among various nanoparticle DDS and various routes of drug administration, which expresses the lack of consistency among studies. Analysis of current literature reveals lipid-and polymer-based DDS as forerunners of DDS for stroke; however, cell membrane-derived vesicles (CMVs) possess the competitive edge due to their innate biocompatibility and superior efficacy. Conversely, inorganic and carbonbased DDS offer different functionalities as well as varied capacity for loading but suffer mainly from poor safety and general lack of investigation in this area. This review supports the existing literature by systematizing presently available data and accounting for the differences in drugs of choice, carrier types, animal models, intervention strategies and outcome parameters.

Oxidative Stress in Ischemia/Reperfusion Injuries following Acute Ischemic Stroke

“…Novel drug design, by dispersing or dissolving the drug within a polymer matrix, entrapping the drug inside lipid vesicles, encapsulating or adsorbing the active molecules on the surface of nanoparticles, are able to improve drug pharmacokinetics, pharmacodynamics and safety, and prevent off-target interactions [213]. Their small size, stability, long serum half-life, and ability to cross the BBB makes them a promising approach to deliver antioxidants in acute ischemic stroke [214], especially since in this setting activation of immune cells and the compromised BBB integrity potentiates the leakage of molecules [215]. The biological activities of nanomaterials, 1-500 nm in size, are related to their size, shape, and surface modifications [216].…”

“…The biological activities of nanomaterials, 1-500 nm in size, are related to their size, shape, and surface modifications [216]. They can be subdivided into [215] PEGylated cerium nanoparticles (NPs) and platinum NPs have been shown to have ROS scavenging properties [215,216], while superparamagnetic iron oxide NPs have been used to deliver under magnetic field guidance endothelial progenitor cells to potentiate angiogenesis [217]. Fullerenes have free radical scavenging potential, while carbon nanotubes were able to carry neural progenitor cells to the lesion site, which differentiated and were integrated with the surviving cells promoting improved behavioral outcomes [215].…”

pH‐Sensitive, Cerebral Vasculature‐Targeting Hydroxyethyl Starch Functionalized Nanoparticles for Improved Angiogenesis and Neurological Function Recovery in Ischemic Stroke

“…Some dual-targeting applications are currently used to improve the targeting performance of nanoparticles. [33,34] Hydroxyethyl starch is often used as an expander in clinical practice. It contains a large number of hydroxyl groups and can be modified for functionalization.…”

Wielding the Double‐Edged Sword of Inflammation: Building Biomaterial‐Based Strategies for Immunomodulation in Ischemic Stroke Treatment

“…[184,185] NPs are typically a few nanometers to 100 nm in size to allow diffusion into the brain parenchyma. [186,187] Zeta potential and shape can affect NP biodistribution. [187] Bioavailability may be further improved by making "stealth" NPs, usually achieved by polyethylene glycol (PEG) coating (PEGylation), to evade opsonization and phagocytosis and prolong systemic circulation time.…”