Novel optimized drug delivery systems for enhancing spinal cord injury repair in rats

Abstract

Effective and accurate delivery of drugs to tissue with spinal cord injury (SCI) is the key to rehabilitating neurological deficits. Sustained-release microspheres (MS) have excellent degradability and can aid in the long-term release of drugs. However, the burst release phenomenon can cause unexpected side effects. Herein, we developed and optimized an injectable poly(lactic-co-glycolic acid) (PLGA) MS loaded with melatonin(Mel), which were mixed further with Laponite hydrogels (Lap/MS@Mel, a micro-gel compound) in order to reduce the burst release of MS. Thus, these MS were able to achieve stable and prolonged Mel release, as well as synergistic Lap hydrogel in order to repair neural function in SCI by in situ injection. In clinical practice, patients with SCI have complicated conditions and significant inter-individual differences, which means that a single route of administration does not meet actual clinical needs. Thus, the nanospheres are synthesized and subsequently coated with platelet membrane (PM) in order to form PM/MS@Mel (nano-PM compound) for sustained and precision-targeted delivery of Mel intravenously in the SCI. Notably, optimized microsphere delivery systems have improved Mel regulation polarization of spinal microglial/macrophages, which can reduce loss of biomaterials due to macrophage-induced immune response during implantation of spinal cord tissue. These two new delivery systems that are based on MS provide references for the clinical treatment of SCI, according to different requirements.

Intestinal microbiota and melatonin in the treatment of secondary injury and complications after spinal cord injury

“…In addition, melatonin can be used in combination with various treatment methods to treat SCI. For instance, polylactic acid glycolic acid copolymer sustained-release microspheres with melatonin and laponite hydrogel for mixed injection to treat SCI ( Zhang M. et al, 2021 ). The use of melatonin in extracellular vesicles of stem cells reduces the levels of N6 methyladenosine modification (m6A) and methyltransferase 3 (METTL3) in SCI, and enhances the stability of USP29mRNA in MSCs, which also promote stem cell proliferation, differentiation, neurosphere formation and secretion of neurotrophic factors ( Li et al, 2017 ; Zheng et al, 2017 ).…”

The Translation of Nanomedicines in the Contexts of Spinal Cord Injury and Repair

“…The common delivery routes for nanomedicine targeting spinal cord pathology are intravenous, intrathecal, intranasal, or intraspinal administration. Nanoparticles can be administered intravenously to allow for systemic distribution throughout the body and potential transport across the B-SCB [12,45,49,50,[85][86][87][88][89][90][91][92][93][94]. Gao et al demonstrated that intravenously administered nanoparticles are localised preferentially and dose-dependently at the lesion site in the spinal cord.…”

Hydrogel scaffolds in the treatment of spinal cord injury: a review

“…Zhang et al developed and optimized injectable PLGA MS loaded with melatonin (Mel), which was further mixed with Laponite hydrogel to form a composite hydrogel scaffold to reduce the sudden release of MS. The MS was able to achieve stable and prolonged Mel release as well as synergistic Lap hydrogel to repair neural function in SCI by in situ injection ( Zhang et al, 2021 ).…”