Inflammatory depression is closely related to neuroinflammation. However, current anti-inflammatory drugs have low permeability to cross blood–brain barrier with difficulties reaching the central nervous system to provide therapeutic effectiveness. To overcome this limitation, the nano-based drug delivery technology was used to synthesize melanin-like polydopamine nanoparticles (PDA NPs) (~ 250 nm) which can cross the blood–brain barrier. Importantly, PDA NPs with abundant phenolic hydroxyl groups function as excellent free radical scavengers to attenuate cell damage caused by reactive oxygen species or acute inflammation. In vitro experiments revealed that PDA NPs exhibited excellent antioxidative properties. Next, we aimed to investigate the therapeutic effect of PDA NPs on inflammatory depression through intraperitoneal injection to the lipopolysaccharide-induced inflammatory depression model in mice. PDA NPs significantly reversed the depression-like behavior. PDA NPs was also found to reduce the peripheral and central inflammation induced by LPS, showing that alleviated splenomegaly, reduced serum inflammatory cytokines, inhibited microglial activation and restored synaptic loss. Various experiments also showed that PDA NPs had good biocompatibility both in vivo and in vitro. Our work suggested that PDA NPs may be biocompatible nano-drugs in treating inflammatory depression but their clinical application requires further study. Graphical Abstract
Cognitive function is an important ability of the brain, but cognitive dysfunction can easily develop once the brain is injured in various neuropathological conditions or diseases. Photobiomodulation therapy is a type of noninvasive physical therapy that is gradually emerging in the field of neuroscience. Transcranial photobiomodulation has been commonly used to regulate neural activity in the superficial cortex. To stimulate deeper brain activity, advanced photobiomodulation techniques in conjunction with photosensitive nanoparticles have been developed. This review addresses the mechanisms of photobiomodulation on neurons and neural networks and discusses the advantages, disadvantages and potential applications of photobiomodulation alone or in combination with photosensitive nanoparticles. Photobiomodulation and its associated strategies may provide new breakthrough treatments for cognitive improvement.
Inflammatory depression is closely related to the activation of the immune system in the peripheral and central nervous system (CNS). Due to the lack of drugs, the treatment of inflammatory depression has been an urgent problem to be solved. According to the anti-oxidative and anti-inflammatory properties, melanin-like polydopamine nanoparticles (PDA NPs), may have a good therapeutic effect on the inflammatory depression. Hence, we investigated the therapeutic effect of PDA NPs on lipopolysaccharide (LPS)-induced inflammatory depression in this study. The PDA NPs with diameter of ~250 nm were prepared by the simplest one-step synthesis method. Applying these PDA NPs to the LPS-induced inflammatory depression mice model confirmed that PDA NPs significantly reversed the depression behavior of mice. Further exploration found that, therapeutic effects of PDA NPs were attributed to their antagonism to the peripheral inflammation induced by LPS. More importantly, PDA NPs also crossed the blood-brain barrier to reach the CNS, and inhibited microglial activation via the TLR4/NF-κB signaling pathway, restoring neuronal synapse loss, which consequently attenuated depression-like behaviors induced by LPS. The PDA NPs were also confirmed to show good biocompatibility both in vivo and in vitro. Our study therefore provided the great promise of PDA NPs as a biocompatible nano-drug in rescuing inflammatory depression.
Background Ultrasound-guided peripheral nerve block is difficult to accurately identify the diffusion location of injected local anesthetics. Moreover, current available local anesthetics are limited in duration, which is inadequate for the treatment of prolonged pain. We designed a drug delivery system by using adhesive polylactic-co-glycolic acid (PLGA) microbubbles loaded with ropivacaine to accurately identify and deliver the local anesthetics to the desired targeted site for prolonged analgesic time in rat pain models. Methods The adhesive PLGA-ropivacaine microbubbles (APRMs) were fabricated by coating polydopamine on the PLGA microbubbles with ropivacaine embedded in the shell. Ropivacaine release and ultrasonographic experiments of APRMs were conducted in vitro. Then, incision surgery and SNI-induced neuropathic pain were conducted for adult male rats to verify the ropivacaine release of APRMs in vivo. Ultrasound imaging was performed to confirm the ultrasonic visualization of APRMs. The in vivo fluorescence imaging experiment was conducted for the adhesion property of APRMs. Finally, systemic toxicity and tissue reaction were histologically evaluated. Results In vivo, these microbubbles were able to accurately identify and release local anesthetics to targeted sites for prolonged analgesia. Results showed that APRMs not only presented a continuous release of ropivacaine for at least 16 days, but also exhibited strong dispersed echo spots in agarose gel. In animal model studies, APRMs alleviated mechanical allodynia and thermal hyperalgesia in neuropathic and postoperative pain, which lasted at least 7 days. More importantly, the APRMs performed a lower agent spread area and longer analgesic time than PRMs and ropivacaine groups in thermal analgesic test. Additionally, histological systemic toxicity and tissue reactions evaluated that APRMs did not display any detectable systemic toxicity or adverse tissue reactions. Conclusions APRMs served as an excellent nerve blocker in this delivery system to achieve accurate, sustainable, and safe analgesic efficacy for pain management.
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