IKBKB siRNA-Encapsulated Poly (Lactic-co-Glycolic Acid) Nanoparticles Diminish Neuropathic Pain by Inhibiting Microglial Activation.

Activation of nuclear factor-kappa B (NF-κB) in microglia plays a decisive role in the progress of neuropathic pain, and the inhibitor of kappa B (IκB) is a protein that blocks the activation of NF-κB and is degraded by the inhibitor of NF-κB kinase subunit beta (IKBKB). The role of IKBKB is to break down IκB, which blocks the activity of NF-kB. Therefore, it prevents the activity of NK-kB. This study investigated whether neuropathic pain can be reduced in spinal nerve ligation (SNL) rats by reducing the activity of microglia by delivering IKBKB small interfering RNA (siRNA)-encapsulated poly (lactic-co-glycolic acid) (PLGA) nanoparticles. PLGA nanoparticles, as a carrier for the delivery of IKBKB genes silencer, were used because they have shown potential to enhance microglial targeting. SNL rats were injected with IKBKB siRNA-encapsulated PLGA nanoparticles intrathecally for behavioral tests on pain response. IKBKB siRNA was delivered for suppressing the expression of IKBKB. In rats injected with IKBKB siRNA-encapsulated PLGA nanoparticles, allodynia caused by mechanical stimulation was reduced, and the secretion of pro-inflammatory mediators due to NF-κB was reduced. Delivering IKBKB siRNA through PLGA nanoparticles can effectively control the inflammatory response and is worth studying as a treatment for neuropathic pain.

FK506-loaded PLGA nanoparticles improve long-term survival of a vascularized composite allograft in a murine model.

BACKGROUND: The side effects of life-long administration of FK506 limit the clinical practice of vascularized composite allografts (VCAs). This study aimed to evaluate the feasibility of FK506-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (FK506 NPs) for prolonging the long-term survival of VCAs and reducing the side effects of FK506. METHODS: PLGA nanoparticles loaded with FK506 were prepared by the solvent evaporation method. The characterization of FK506 NPs was evaluated by electron microscopy. To confirm the function and safety of FK506 NPs, these particles were administrated into rats by intraperitoneal injection. The survival time of the allograft, systemic concentration of FK506, anti-rejection activity, and side-effect of FK506 NPs were evaluated in a Brown Norway (BN)-to-Sprague Dawley (SD) epigastric VCA transplantation model. RESULTS: Compared with the nontreatment, PLGA control and FK506 groups, the median survival times (MST) of the FK506 NP groups were significantly prolonged. The FK506 NPs could maintain therapeutic drug concentration for 60 days. Moreover, cytokine concentrations, flow cytometry of regulatory T cells (Tregs) and histopathology of allografts revealed significantly prolonged immunosuppression by FK506 NPs. FK506 NPs also ameliorated FK506 nephrotoxicity. CONCLUSIONS: FK506 NPs prolong the survival time of VCAs in a murine model with minimal nephrotoxicity, and provide a potential clinical strategy for ameliorating long-term side effects of immunosuppressive therapy.

Optimization and characterization of poly(lactic-co-glycolic acid) nanoparticles loaded with astaxanthin and evaluation of anti-photodamage effect in vitro.

Astaxanthin is a xanthophyll carotenoid with high beneficial biological activities, such as antioxidant function and scavenging oxygen free radicals, but its application is limited because of poor water solubility and low bioavailability. Here, we prepared and optimized poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with astaxanthin using the emulsion solvent evaporation technique and investigated the anti-photodamage effect in HaCaT cells. The four-factor three-stage Box-Behnken design was used to optimize the nanoparticle formulation. The experimental determination of the optimal nanoparticle size was 154.4 ± 0.35 nm, the zeta potential was 22.07 ± 0.93 mV, encapsulation efficiency was 96.42 ± 0.73% and drug loading capacity was 7.19 ± 0.12%. The physico-chemical properties of the optimized nanoparticles were characterized by dynamic light scattering, scanning electron microscopy, transmission electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry and thermo-gravimetric analyser. In vitro study exhibited the excellent cell viability and cellular uptake of optimized nanoparticles on HaCaT cells. The anti-photodamage studies (cytotoxicity assay, reactive oxygen species content and JC-1 assessment) demonstrated that the optimized nanoparticles were more effective and safer than pure astaxanthin in HaCaT cells. These results suggest that our PLGA-coated astaxanthin nanoparticles synthesis method was highly feasible and can be used in cosmetics or the treatment of skin diseases.