Structural, blood flow and functional changes in the macular area and the expression of aqueous humor factors in myopia.

Objective: To compare the macular area parameters and aqueous humor factors between myopia and emmetropia. Methods: Convenience sampling was used to select patients who visited the Changzhi Aier Eye Hospital's department of ophthalmology from December 2018 to December 2022 as the study participants. They were divided into three groups according to whether they were diagnosed as mild myopia myopic, highly myopic or not as follows: the mild myopia group (60 cases, 108 eyes), the high myopia group (46 cases, 78 eyes) and the healthy emmetropia group (40 cases, 65 eyes). The differences in the macular integrity (MI) assessment, optical coherence tomography and optical coherence tomography angiography parameters and aqueous humor factors were compared between the three groups. Results: AL in high myopia group was the highest, and that in emmetropia group was the lowest. The BCVA of mild myopia group was the highest. The RS in the high myopia group were significantly lowest in the three groups (26.42 ± 1.04 vs. 28.34 ± 0.76 vs. 31.92 ± 0.77) (F = 5.374, p = 0.013). The 63% BCEA, 95% BCEA and MI in the high myopia group were significantly highest (p < 0.05). The mean RPE thickness, mean CT and mean RT in the high myopia group were lowest (p < 0.05). The blood flow density were lowest in the superficial fovea, paracentral fovea and different subdivisions of the paracentral fovea in the high myopia group (p < 0.05). The VEGF concentration in the aqueous humor of the high myopia group was lowest (25.62 ± 17.43 vs. 32.45 ± 24.67 vs. 64.37 ± 21.14) (F = 9.237, p < 0.001). The MMP-2 concentration was highest (483 ± 201.48 vs. 410 ± 142.37 vs. 386 ± 154.34) (F = 5.542, p = 0.018). The VEGF concentration in the aqueous humor factor was negatively correlated with the AL in the myopia group (r = -0.438, p = 0.002), the MMP-2 concentration was positively correlated with the AL (r = 0.484, p = 0.010). Conclusion: Patients with high myopia showed decreased retinal light sensitivity, fixation stability, superficial blood flow density and retinal thickness compared with people with emmetropia. A decreased VEGF concentration and increased MMP-2 concentration in the aqueous humor factor have potential associations with the development of high myopia.

Sensitive fluorometric determination of platelet-derived growth factor BB and avian influenza A virus DNA via dual signal amplification using the hybridization chain reaction and glucose oxidase assisted recycling.

A method is described for fluorometric determination of platelet-derived growth factor BB (PDGF-BB) and avian influenza A (H1N1) virus DNA. It is based on the use of the hybridization chain reaction (HCR) and of glucose oxidase (GOx) assisted dual-recycling amplification. A silver coated glass slide (SCGS) serves as an ideal material for separation. A signal DNA/initiator triggers the HCR and generates a cascade of hybridization to form a nicked double-helix polymer. Upon addition of the analytes (PDGF-BB or H1N1 DNA) and capture DNA immobilized on the SCGS, the nicked double-helix polymer binds on the surface of the SCGS through formation of a [capture DNA/analyte/signal DNA] sandwich structure. The GOx-biotin-streptavidin (SA) complexes were then attached to the nicked double-helix polymer through SA-biotin interaction. After cleavage by DNase I, the bound GOx is transferred into the buffer. Glucose is added and enzymatically oxidized to produce H2O2. The H2O2 formed oxidizes the substrate 3-(p-hydroxyphenyl)-propanoic acid to give a blue fluorescent product (with excitation/emission maxima at 320/416 nm) under the catalysis of horseradish peroxidase. Under optimal conditions, fluorescence increases linearly in the 0.5 to 70 pmol·L-1 PDGF-BB concentration range, and the detection limit is 191 fmol·L-1. For the H1N1 virus DNA, the respective data are 2.5 to 300 pmol·L-1 and 826 fmol·L-1. Graphical abstract Schematic presentation for detection of analytes (PDGF-BB or H1N1 virus DNA) based on the dual-signal amplification of Hybridization Chain Reaction (HCR) and glucose oxidase (GOx) using silver coated glass slide (SCGS) as separation material.

In vivo biodistribution, anti-inflammatory, and hepatoprotective effects of liver targeting dexamethasone acetate loaded nanostructured lipid carrier system.

We aimed to evaluate whether the enhancement of the liver accumulation and anti-inflammatory activity of dexamethasone acetate (DXMA) could be achieved by incorporating it into nanostructured lipid carrier (NLCs). DXMA-NLCs were prepared using a film dispersion-ultrasonication method and characterized in terms of particle size, PDI, zeta potential, differential scanning calorimetry, drug loading capacity, encapsulation efficiency, and in vitro release. The biodistribution and pharmacokinetics of DXMA-NLCs in mice were significantly different from those of the DXMA solution (DXMA-sol). The peak concentration of DXMA-NLCs was obtained half an hour after intravenous administration. More than 55.62% of the total administrated dose was present in the liver. An increase of 2.57 fold in the area under the curve was achieved when compared with that of DXMA-sol. DXMA-NLCs exhibited a significant anti-inflammatory and hepatoprotective effect on carrageenan-induced rats and carbon tetrachloride-induced mice compared with DXMA-sol. However, the effect was not in proportion to the dosage. The intermediate and low dosages presented better effects than DXMA-sol. All results indicate that NLCs, as a novel carrier for DXMA, has potential for the treatment of liver diseases, increasing the cure efficiency and decreasing the side effects on other tissues.

In vitro cytotoxicity, in vivo biodistribution and antitumor activity of HPMA copolymer-5-fluorouracil conjugates.

5-Fluorouracil (5-FU) is an antimetabolite with a broad-spectrum activity against solid tumors. However, its very short half-life in plasma circulation greatly limited the in vivo antitumor efficacy and clinical application. The current work aimed to solve this problem as well as to increase 5-FU biodistribution to tumor by covalently conjugating 5-FU to a biocompatible, non-toxic and non-immunogenic drug carrier -N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer. The in vitro cytotoxicity, in vivo biodistribution and therapeutic efficacy of HPMA copolymer-5-FU conjugates (P-FU) were reported. Cytotoxicity was evaluated by using a serial of tumor cells (A549, CT-26, Hela, HepG(2) cells and 5-FU resistant HepG(2) cells). In vivo biodistribution and therapeutic efficacy were investigated in Kunming mice-bearing hepatoma 22 (H(22)). Results indicated that P-FU could increase the cytotoxicity of 5-FU in Hela, HepG(2) and 5-FU resistant HepG(2) cells, while it decreases the cytotoxicity of 5-FU in A549 and CT-26. Both in vitro release profile in plasma and biodistribution study showed that P-FU significantly prolonged the drug plasma circulation time. P-FU also showed an over 3-fold larger area under the concentration-time curve (AUC) in tumor when compared with free drug. Therapeutic evaluation also demonstrated that the treatment with P-FU displayed stronger inhibition of the tumor growth when compared with that of control group (physiologic saline) or 5-FU group at the same dose. All the results suggested that P-FU could increase cytotoxicity of 5-FU in certain cancer cell lines, prolong 5-FU circulation time in vivo, enhance 5-FU distribution to tumor and improve therapeutic efficacy. Therefore, HPMA copolymer is a potential carrier for 5-FU for the effective treatment of cancer.

In vitro and in vivo study of N-trimethyl chitosan nanoparticles for oral protein delivery.

In this study, the effects of alginate modification on absorption properties of FITC-BSA loaded TMC nanoparticles were investigated on an in vitro model of GI epithelium (Caco-2 cells). The feasibility of applying TMC nanoparticles loaded with a model vaccine urease in oral vaccination was also studied. Alginate modified TMC nanoparticles showed higher FITC-BSA permeate efficiency than non-modified TMC nanoparticles. However, alginate modification barely had any effect on TMC nanoparticles' property of decreasing TEER or enhancing drug paracellular transport. Mice s.c. immunized with urease loaded TMC nanoparticles showed highest systematic immune response (IgG levels) but the lowest mucosal response (secretory IgA levels). In the contrast, mice i.g. immunized with urease loaded TMC nanoparticles showed much higher antibody titers of both IgG and secretory IgA than those with urease solution or urease co-administrated with TMC solution. These results indicated that TMC nanoparticles are potential carriers for oral protein and vaccine delivery.

Lung-targeting delivery of dexamethasone acetate loaded solid lipid nanoparticles.

The objective of the present study was to develop a novel solid lipid nanoparticle (SLN) for the lung-targeting delivery of dexamethasone acetate (DXM) by intravenous administration. DXM loaded SLN colloidal suspensions were prepared by the high pressure homogenization method. The mean particle size, drug loading capacity and drug entrapment efficiency (EE%) of SLNs were investigated. In vitro drug release was also determined. The biodistribution and lung-targeting efficiency of DXM-SLNs and DXM-solutions (DXM-sol) in mice after intravenous administration were studied using reversed-phase high-performance liquid chromatography (HPLC). The results (expressed as mean +/- SD) showed that the DXM-SLNs had an average diameter of 552 +/- 6.5 nm with a drug loading capacity of 8.79 +/- 0.04% and an entrapment efficiency of 92.1 +/- 0.41%. The in vitro drug release profile showed that the initial burst release of DXM from DXM-SLNs was about 68% during the first 2 h, and then the remaining drug was released gradually over the following 48 hours. The biodistribution of DXM-SLNs in mice was significantly different from that of DXM-sol. The concentration of DXM in the lung reached a maximum level at 0.5 h post DXM-SLNs injection. A 17.8-fold larger area under the curve of DXM-SLNs was achieved compared to that of DXM-sol. These results indicate that SLN may be promising lung-targeting drug carrier for lipophilic drugs such as DXM.