Paclitaxel-incorporated nanoparticles improve functional recovery after spinal cord injury

Abstract

As a worldwide medical problem, spinal cord injury has no clear and effective treatment to improve its prognosis. Hence, new treatment strategies for spinal cord injury with good therapeutic efficacy have been actively pursued. As a new drug loading system, acetal dextran nanoparticles (SAD) have good biocompatibility and biodegradability. Therefore, we designed spermine-functionalized acetal-dextran (SAD) nanoparticles and encapsulated paclitaxel (PCL) into them. This design can ensure the sustained release of paclitaxel in the injured area for 4 days and promote the extension of nerve processes in vitro. In our experiment, we found that paclitaxel-loaded SAD nanoparticles (PCL@SAD) decreased the level of chondroitin sulfate proteoglycan in the rat spinal cord injury model, which reduced the scar repair of the injured site and changed the inhibitory environment after spinal cord injury. This reveals that PCL@SAD can effectively protect the injured spinal cord and ultimately improve the functional recovery of the injured spinal cord. One single injection of PCL@SAD shows better therapeutic effect than that of PCL. This study opens an exciting perspective toward the application of neuroprotective PCL@SAD for the treatment of severe neurological diseases.

Injectable Near-Infrared Photothermal Responsive Drug-Loaded Multiwalled Carbon Nanotube Hydrogels for Spinal Cord Injury Repair

“…Further on, [PTX/VEGF]@DMWCNTs/GG microspheres were prepared by microfluidic technology. Compared with other methods for microsphere fabrication such as single emulsion, phase separation, spray drying, and membrane emulsification, microfluidic technology has many advantages, such as the ability to control microsphere shape and size, high drug loading capacity, and control over the physical and chemical properties of microspheres by manipulating solvent type and polymer concentration. , Hydrogel microspheres hold great promise for tissue repair applications, such as cellular and drug therapy delivery. , In this study, GG was selected to prepare the hydrogel microspheres. GG is a thermosensitive hydrogel scaffold that is a transparent solution at elevated temperatures and a transparent solid at low temperatures. , GG possesses unique physical and chemical properties, such as the ability to form a gel through both thermal and ion-cross-linking mechanisms. , In this study, Ca 2+ was used to induce GG gelation.…”

“…However, there are still many obstacles in using hydrogel scaffolds for treating SCI, including difficulties in nerve conduction and synaptic connection, which make functional reconstruction difficult to achieve, thus failing to meet the needs of clinical patients. 38 One of the main reasons is that axonal growth and extension are restricted, making it difficult to establish synaptic connections with severed neurons. Transplants with appropriate mechanical properties, biocompatibility, morphology, and pore structure can provide mechanical support for axonal growth and promote the growth of implanted NSCs.…”

“…PTX can inhibit mitosis and stabilize microtubule formation, which is crucial for tissue regeneration of SCI. Zhang et al 38 found that PTX-loaded nanoparticles reduced the level of chondroitin sulfate proteoglycan in the rat SCI model, thereby reducing scar repair at the injury site and changing the inhibitory environment after SCI. Endothelial cells play a crucial role in angiogenesis, serving as the key cell type for blood vessel formation and functional maintenance.…”

“…Compared with other methods for microsphere fabrication such as single emulsion, phase separation, spray drying, and membrane emulsification, microfluidic technology has many advantages, such as the ability to control microsphere shape and size, high drug loading capacity, and control over the physical and chemical properties of microspheres by manipulating solvent type and polymer concentration. 38,41 Hydrogel microspheres hold great promise for tissue repair applications, such as cellular and drug therapy delivery. 14,42 In this study, GG was selected to prepare the hydrogel microspheres.…”

“…Hydrogel scaffolds have aroused great interest due to their similar mechanical properties to the spinal cord and their three-dimensional network structure that creates a suitable stereoscopic microenvironment for cell attachment. However, there are still many obstacles in using hydrogel scaffolds for treating SCI, including difficulties in nerve conduction and synaptic connection, which make functional reconstruction difficult to achieve, thus failing to meet the needs of clinical patients . One of the main reasons is that axonal growth and extension are restricted, making it difficult to establish synaptic connections with severed neurons.…”