Protective Effect of Cholic Acid-Coated Poly Lactic-Co-Glycolic Acid (PLGA) Nanoparticles Loaded with Erythropoietin on Experimental Stroke.

Stroke is a major cause of adult mortality and morbidity worldwide. However, the treatment of stroke using the vast majority of possible drug candidates, including erythropoietin (EPO), remains problematic because of the presence of the blood-brain barrier (BBB), resulting in scarce penetration onto the brain. To overcome this, we synthesized a novel EPO delivery system, namely the cholic acid-coated poly lactic-co-glycolic acid (PLGA) nanoparticles loaded with EPO (EPO-CA-NPs), with the aim of enabling efficient penetration of EPO-CA-NPs across the BBB. The therapeutic efficacy of EPO-CA-NPs on an animal model of stroke was compared with that of EPO. The experimental stroke model was produced by subjecting rats to the middle carotid artery occlusion and reperfusion (MCAO/R) technique. The results indicated that EPO-CA-NPs reduced the extent of the infarct volume and cellular apoptosis to a greater extent than EPO alone at postoperative day (POD) 1. Furthermore, EPO-CA-NPs showed better performance on sensorimotor functions than EPO alone at POD 1, 3, 5, and 7. Taken together, EPO-CA-NPs, a newly synthesized brain-targeted EPO-delivery system, has stronger therapeutic effects on stroke than EPO alone, by enabling efficient EPO delivery into the brain.

Protective effects of poly(lactic-co-glycolic acid) nanoparticles loaded with erythropoietin stabilized by sodium cholate against glutamate-induced neurotoxicity.

The final aim of this study was to confirm the neuroprotective effects of recombinant human erythropoietin (rhEPO)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles stabilized by sodium cholate (rhEPO-Ch-NP) and compare their effects with those of rhEPO using an in vitro model of cerebral ischemia. Glutamate-induced excitotoxic damage on SH-SY5Y cells, a human neuroblastoma cell line, with or without rhEPO-Ch-NPs was quantitatively evaluated. The rhEPO-Ch-NPs were carefully prepared using a water-in-oil-in-water (w/o/w) emulsion solvent evaporation technique with PLGA, sodium cholate hydrate, and ethyl acetate. The rhEPO-Ch-NPs were fully characterized by both transmission electron microscopy (TEM) and differential scanning calorimetry (DSC). In addition, significant intracellular uptake of these particles was monitored by confocal microscopy. Notably, the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and nuclear changes observed by 4',6-diamidino-2-phenylindole (DAPI) staining in SH-SY5Y cells demonstrated that rhEPO-Ch-NPs were safer at any concentration investigated and rescued more neuronal cells, while preserving normocytic features against glutamate-induced excitotoxic damages compared to rhEPO.

Neuroprotective effect of estradiol-loaded poly(lactic-co-glycolic acid) nanoparticles on glutamate-induced excitotoxic neuronal death.

Different concentrations of estradiol (E2)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (E2-PLGA-NPs) were synthesized using the emulsion-diffusion method. Transmission electron microscopy results showed that the average particle size of E2-PLGA-NPs was 98 ± 1.9 nm when stabilized with polyvinyl alcohol and 103 ± 4.9 nm when stabilized with Tween-80. Fourier transform-infrared spectroscopy with diamond attenuated total reflectance was used to identify the presence or absence of E2 molecules in PLGA nanocapsules. Cell proliferation was assessed after treating SH-SY5Y neuroblastoma cells with 1 nM-1 µM of E2 and E2-PLGA-NPs. The neuroprotective efficacy against glutamate-induced excitotoxicity was also investigated in SH-SY5Y neuroblastoma cells. Neuroprotection was greater in E2-PLGA-NP-treated cells than in cells treated with the same concentration of E2. Furthermore, E2- and E2-PLGA-NP-treated cells expressed more p-ERK1/2 and p-CREB than cells treated with glutamate only. Moreover, the expression of p-ERK1/2 was higher than that of p-CREB. In this study, p-ERK1/2 had a greater influence on the neuroprotective effect of E2 and E2-PLGA-NPs than p-CREB.

Fabrication of atelocollagen-coated bioabsorbable suture and the evaluation of its regenerative efficacy in Achilles tendon healing using a rat experimental model.

Recently, the incidence of Achilles tendon ruptures (ATRs) has become more common, and repair surgery using a bioabsorbable suture is generally preferred, particularly in the case of healthy patients. Sutures composed of poly(lactic-co-glycolic acid) (PLGA) are commonly used in ATR surgeries. Nevertheless, owing to the inherent limitations of PLGA, novel bioabsorbable sutures that can accelerate Achilles tendon healing are sought. Recently, several studies have demonstrated the beneficial effects of atelocollagen on tendon healing. In this study, poly(3,4-dihydroxy-L-phenylalanine) (pDOPA), a hydrophilic biomimetic material, was used to modify the hydrophobic surface of a PLGA suture (Vicryl, VC) for the stable coating of atelocollagen on its surface. The main objective was to fabricate an atelocollagen-coated VC suture and evaluate its performance in the healing of Achilles tendon using a rat model of open repair for ATR. Structural analyses of the surface-modified suture indicated that the collagen was successfully coated on the VC/pDOPA suture. Postoperative in vivo biomechanical analysis, histological evaluation, ultrastructural/morphological analyses, and western blotting confirmed that the tendons in the VC/pDOPA/Col group exhibit superior healing than those in the VC and VC/pDOPA groups after 1 and 6 weeks following the surgery. The this study suggests that atelocollagen-coated PLGA/pDOPA sutures are preferable for future medical applications, especially in the repair of ATR.

Topical film prepared with Rhus verniciflua extract-loaded pullulan hydrogel for atopic dermatitis treatment.

Atopic dermatitis (AD) is characterized by relapsing pruritus and skin dryness. Due to the pathogenic multiplicity and the adverse effects associated with the current therapeutics, development of transdermal drug delivery system is becoming an area of interest. Here, a novel topical film prepared with Rhus verniciflua extract (RVE)-loaded pullulan hydrogel (RVE@PH) was synthesized and tested its therapeutic efficacy on the AD rats modeled by neonatal capsaicin injection method. The RVE@PH was characterized by a Fourier-transform infrared spectroscopy and an in vitro release assay. Rat pups were randomly divided into two groups: vehicle-treated (VEH; n = 5) and capsaicin-treated (n = 15). The latter were given capsaicin subcutaneously at 24 h after birth for AD induction and further divided into three groups (n = 5 per each): not treated (CAP), pullulan hydrogel-applied (PH), and RVE@PH-applied (RVE-PH). The pullulan hydrogel and RVE@PH were topically applied on shoulder lesions for 14 days (from 42 to 56 days after birth). Their phenotypes were compared based on the dermatitis score, epidermal thickness, mast cell infiltration, and serum myeloperoxidase (MPO) activities. The PH group showed significant attenuation in all the aforementioned values compared to the CAP group, suggesting that pullulan hydrogel itself has therapeutic activity against AD. Notably, the attenuations were more potent in the RVE-PH group than the PH group, indicating that the therapeutic efficacy against AD is augmented by the presence of RVE, a loaded pharmaceutic. Collectively, these results indicate that RVE@PH inhibits AD through exerting the dual roles, that is, the pullulan hydrogel-mediated physical and RVE-mediated pharmaceutical actions. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2325-2334, 2019.