Efficient Delivery of Nerve Growth Factors to the Central Nervous System for Neural Regeneration

Abstract

The central nervous system (CNS) plays a central role in the control of sensory and motor functions, and the disruption of its barriers can result in severe and debilitating neurological disorders. Neurotrophins are promising therapeutic agents for neural regeneration in the damaged CNS. However, their penetration across the blood–brain barrier remains a formidable challenge, representing a bottleneck for brain and spinal cord therapy. Herein, a nanocapsule‐based delivery system is reported that enables intravenously injected nerve growth factor (NGF) to enter the CNS in healthy mice and nonhuman primates. Under pathological conditions, the delivery of NGF enables neural regeneration, tissue remodeling, and functional recovery in mice with spinal cord injury. This technology can be utilized to deliver other neurotrophins and growth factors to the CNS, opening a new avenue for tissue engineering and the treatment of CNS disorders and neurodegenerative diseases.

Stimuli‐Responsive Delivery of Growth Factors for Tissue Engineering

“…As shown in Figure 6C, in vitro release of n (NGF) under different pH conditions (6.0 and 7.4) validated pH sensitive property of the nanocapsules where n (NGF) can be continuously released for days but with a higher rate under acidic pH = 6.0. [ 165 ]…”

“…An efficient pH responsive growth factor nanocapsule that has the potential to cross the BBB was applied for neural regeneration in CNS. [ 165 ] A) Schematic for the preparation and application of this responsive delivery system. B) TEM images and zeta potential of NGF nanocapsule.…”

Enhanced Delivery of Rituximab Into Brain and Lymph Nodes Using Timed-Release Nanocapsules in Non-Human Primates

“…Moreover, such nanocapsules can effectively penetrate the BBB and deliver encapsulated macromolecules to the CNS via nicotinic acetylcholine receptors and choline transporters (30). This technology has demonstrated efficacy for neural regeneration in mice with spinal cord injuries (31) and antibody therapies for primary brain tumors (32) in mice.…”

An Antioxidant Enzyme Therapeutic for COVID‐19

“…[26,27] As illustrated in Scheme 1C, 2-methacryloyloxyethyl phosphorylcholine (MPC), N-(3-aminopropyl) methacrylamide hydrochloride (APM), and N,N'-methylenebisacrylamide (BIS) are used as the monomers and crosslinker. These molecules are enriched around the catalase molecules through noncovalent interactions; [28,29] subsequent polymerization grows a thin polymeric shell around individual catalase molecules, forming nanocapsules denoted as n(CAT). The thin shell protects the enzyme, while allowing H 2 O 2 to rapidly transport through, endowing n(CAT) with high enzyme activity, augmented stability, and improved plasma half-life.…”