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12. Analysis of Factors Affecting Power Grid Investment Based on Johansen Cointegration Analysis Theory

Author

Zhang, Wang, Nan, Kaihui, Yang, Qinggang, Zhang, Jianfeng, Chen, Hong, Zhang, Xinyan, Kacprzyk, Janusz, Series Editor, Pal, Nikhil R., Advisory Editor, Bello Perez, Rafael, Advisory Editor, Corchado, Emilio S., Advisory Editor, Hagras, Hani, Advisory Editor, Kóczy, László T., Advisory Editor, Kreinovich, Vladik, Advisory Editor, Lin, Chin-Teng, Advisory Editor, Lu, Jie, Advisory Editor, Melin, Patricia, Advisory Editor, Nedjah, Nadia, Advisory Editor, Nguyen, Ngoc Thanh, Advisory Editor, Wang, Jun, Advisory Editor, Xu, Zheng, editor, Choo, Kim-Kwang Raymond, editor, Dehghantanha, Ali, editor, Parizi, Reza, editor, and Hammoudeh, Mohammad, editor

Published
2020
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14. Controlled Release of Dexamethasone From an Intravitreal Delivery System Using Porous Silicon DioxideControlled Release of Intravitreal Dexamethasone

Author

Hou, Huiyuan, Wang, Chengyun, Nan, Kaihui, Freeman, William R, Sailor, Michael J, and Cheng, Lingyun

Subjects
Biomedical and Clinical Sciences, Ophthalmology and Optometry, Eye Disease and Disorders of Vision, Bioengineering, Neurosciences, Neurodegenerative, Nanotechnology, Animals, Capillary Permeability, Cells, Cultured, Delayed-Action Preparations, Dexamethasone, Disease Models, Animal, Drug Delivery Systems, Fluorescein Angiography, Follow-Up Studies, Fundus Oculi, Glucocorticoids, Intravitreal Injections, Porosity, Rabbits, Retinal Diseases, Retinal Vessels, Silicon Dioxide, Tomography, Optical Coherence, Vitreous Body, porous silicon, mesopores, controlled drug release, intravitreal drug delivery, dexamethasone, rabbit eye, Biological Sciences, Medical and Health Sciences, Ophthalmology & Optometry, Ophthalmology and optometry
Abstract

PurposeThe current study aims to evaluate a porous silicon-based drug delivery system meant for sustained delivery of dexamethasone (Dex) to the vitreous and retina.MethodsDexamethasone was grafted covalently into the pore walls of fully oxidized porous silicon particles (pSiO2-COO-Dex), which then was evaluated for the pharmacological effect of the payload on cultured ARPE19 cells before intravitreal injection. The Dex release profile was investigated in a custom designed dynamic dissolution chamber to mimic the turnover of vitreous fluid in rabbit eyes. Ocular safety, in vivo release, and pharmacodynamics were evaluated in rabbit eyes, and the human VEGF-induced rabbit retinal vascular permeability model.ResultsLoading efficiency of Dex was 69 ± 9 μg per 1 mg of the pSiO2-COO-Dex particles. Dynamic in vitro release demonstrated a sustained mode when compared to free Dex, with the drug half-life extended by 5 times. The released Dex was unaltered and biologically active. In vivo drug release in rabbit eyes revealed a mode similar to the release seen in vitro, with a vitreous half-life of 11 days. At 2 and 4 weeks after a single intravitreal injection of pSiO2-COO-Dex particles (mean 2.71 ± 0.47 mg), intravitreal 500 ng of VEGF did not induce significant retinal vessel dilation or fluorescein leakage, while these events were observed in the eyes injected with empty pSiO2 particles or with free Dex. The retinal vessel score from fluorescein angiography for the control eyes was double the score for the eyes injected with pSiO2-COO-Dex. No adverse reaction was observed for the eyes injected with drug-loaded pSi particles during the course of the study.ConclusionsThe porous silicon-based Dex delivery system (pSiO2-COO-Dex) can be administered safely into vitreous without toxicity. Dex release from the porous silicon particles was sustained for 2 months and was effective against VEGF-induced retinal vessel reaction.

Published
2016

15. A sustained intravitreal drug delivery system with remote real time monitoring capability

Author

Hou, Huiyuan, Nieto, Alejandra, Belghith, Akram, Nan, Kaihui, Li, Yangyang, Freeman, William R, Sailor, Michael J, and Cheng, Lingyun

Subjects
Engineering, Biomedical Engineering, Nanotechnology, Bioengineering, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Animals, Dexamethasone, Drug Delivery Systems, Drug Monitoring, Rabbits, Retinal Diseases, Sirolimus, Video Recording, Intravitreal drug delivery, Porous silicon, Drug release monitoring, Rapamycin
Abstract

Many chorioretinal diseases are chronic and need sustained drug delivery systems to keep therapeutic drug level at the disease site. Many intravitreal drug delivery systems under developing do not have mechanism incorporated for a non-invasive monitoring of drug release. The current study prepared rugate porous silicon (pSi) particles by electrochemical etching with the current frequency (K value) of 2.17 and 2.45. Two model drugs (rapamycin and dexamethasone) and two drug-loading strategies were tested for the feasibility to monitor drug release from the pSi particles through a color fundus camera. The pSi particles (k=2.45) with infiltration loading of rapamycin demonstrated progressively more violet color reflection which was negatively associated with the rapamycin released into the vitreous (r=-0.4, p

Published
2015

16. Micelle formulation of hexadecyloxypropyl-cidofovir (HDP-CDV) as an intravitreal long-lasting delivery system

Author

Ma, Feiyan, Nan, Kaihui, Lee, SuNa, Beadle, James R, Hou, Huiyuan, Freeman, William R, Hostetler, Karl Y, and Cheng, Lingyun

Subjects
Medical Biotechnology, Biomedical and Clinical Sciences, Neurosciences, Sexually Transmitted Infections, Biotechnology, Infectious Diseases, Eye Disease and Disorders of Vision, 5.1 Pharmaceuticals, Animals, Antiviral Agents, Chemistry, Pharmaceutical, Cytosine, Delayed-Action Preparations, Drug Delivery Systems, Guinea Pigs, Half-Life, Herpes Simplex, Herpesvirus 1, Human, Intravitreal Injections, Micelles, Organophosphonates, Prodrugs, Rabbits, Retina, Vitreous Body, Micelles formulation, Intravitreal drug delivery, Cidofovir, Lipid prodrug, Herpes simplex virus-1 retinitis, Rabbit eye, Guinea pig eye, 2-Propanol, Dextrose, Disodium hydrogen phosphate, Formaldehyde, Formic acid, Glutaraldehyde, Hexadecyloxypropyl-cidofovir, Methanol, Pentane, Pharmacology and Pharmaceutical Sciences, Pharmacology & Pharmacy, Pharmacology and pharmaceutical sciences
Abstract

There still is an unmet need for a safe and sustained intravitreal drug delivery system. In this study we are proposing and characterizing a micelle based, clear-media intravitreal drug delivery system using the lipid derivatized nucleoside analog, hexadecyloxypropyl-cidofovir (HDP-CDV, CMX 001). HDP-CDV forms micelles in water and in vitreous supernatant with the critical micelle concentration of 19 μg/mL and 9 μg/mL, respectively at 37 °C. The formed micelles had the average size of 274.7 nm and the Zeta potential of -47.1 mV. Drug release study in the excised rabbit vitreous showed a sustained release profile with a half-life of 2.7 days. The micelle formulation of HDP-CDV demonstrated a good safety profile in two animal species (rabbit and guinea pig) following intravitreal injection. The sustained efficacy was tested in a pretreatment study design and the drug potency was tested in an ongoing herpes simplex virus (HSV-1) retinitis model. The pretreatment studies using single intravitreal injection and later HSV-1 infection revealed at least 9 weeks of vitreous presence and therapeutic level of HDP-CDV, with 71% eyes protection from infection. The treatment study demonstrated that intravitreal administration halted active HSV-1 retinitis in 80% of the infected eyes while cidofovir (CDV) treatment failed to suppress active HSV-1 retinitis. In summary, lipid derivatized nucleoside analogs can be formulated as a micelle intravitreal injection and provides a sustained drug release in vitreous for chronic retinal diseases.

Published
2015

17. Intravitreal controlled release of dexamethasone from engineered microparticles of porous silicon dioxide

Author

Wang, Chengyun, Hou, Huiyuan, Nan, Kaihui, Sailor, Michael J, Freeman, William R, and Cheng, Lingyun

Subjects
Biomedical and Clinical Sciences, Ophthalmology and Optometry, Aging, Eye Disease and Disorders of Vision, Eye, Animals, Delayed-Action Preparations, Dexamethasone, Disease Models, Animal, Drug Delivery Systems, Glucocorticoids, Particle Size, Porosity, Rabbits, Retinal Diseases, Silicon Dioxide, Treatment Outcome, Vitreous Body, Intravitreal drug delivery, Porous silicon particle, Sustained release, Rabbit eye, Medical Biochemistry and Metabolomics, Neurosciences, Opthalmology and Optometry, Ophthalmology & Optometry, Ophthalmology and optometry
Abstract

Dexamethasone is a glucocorticoid that is widely used in the ophthalmic arena. The recent FDA approved dexamethasone implant can provide a three month efficacy but with high rate of drug related cataract and high intraocular pressure (IOP). It seems that higher steroid in aqueous humor and around lens may be associated with these complications based on clinical fact that higher IOP was observed with intravitreal triamcinolone acetonide (TA) than with subtenon TA. We hypothesize that placing a sustained dexamethasone release system near back of the eye through a fine needle can maximize efficacy while mitigate higher rate of IOP rise and cataract. To develop a sustained intravitreal dexamethasone delivery system, porous silicon dioxide (pSiO2) microparticles were fabricated and functionalized with amines as well as carboxyl groups. Dexamethasone was conjugated to pSiO2 through the Steglich Esterification Reaction between hydroxyl of dexamethasone and carboxyl groups on the pSiO2. The drug loading was confirmed by Fourier transform infrared spectroscopy (FTIR) and loading efficiency was quantitated using thermogravimetric analysis (TGA). In vitro release was conducted for three months and dexamethasone was confirmed in the released samples using liquid chromatography-tandem mass spectrometry (LC/MS/MS). A pilot ocular safety and determination of vitreous drug level was performed in rabbit eyes. The drug loading study demonstrated that loading efficiency was from 5.96% to 10.77% depending on the loading reaction time, being higher with longer loading reaction time before reaching saturation around 7 days. In vitro drug release study revealed that dexamethasone release from pSiO2 particles was sustainable for over 90 days and was 80 days longer than free dexamethasone or infiltration-loaded pSiO2 particle formulation in the same setting. Pilot in vivo study demonstrated no sign of ocular adverse reaction in rabbit eyes following a single 3 mg intravitreal injection and free drug level at 2-week was 107.23 ± 10.54 ng/mL that is well above the therapeutic level but only around 20% level of dexamethasone released from OZURDEX(®) (dexamethasone intravitreal implant) in a rabbit eye model. In conclusion, dexamethasone is able to covalently load to the pSiO2 particles and provide sustained drug release for at least 3 months in vitro. Intravitreal injection of these particles were well tolerated in rabbit eyes and free drug level in vitreous at 2-week was well above the therapeutic level.

Published
2014

18. Porous silicon oxide–PLGA composite microspheres for sustained ocular delivery of daunorubicin

Author

Nan, Kaihui, Ma, Feiyan, Hou, Huiyuan, Freeman, William R, Sailor, Michael J, and Cheng, Lingyun

Subjects
Chemical Engineering, Engineering, Nanotechnology, Bioengineering, Absorption, Physicochemical, Administration, Ophthalmic, Adsorption, Anti-Bacterial Agents, Capsules, Daunorubicin, Delayed-Action Preparations, Diffusion, Lactic Acid, Materials Testing, Polyglycolic Acid, Polylactic Acid-Polyglycolic Acid Copolymer, Porosity, Silicon Dioxide, Porous silicon oxide, Poly(DL-lactide-co-glycolide), Ocular drug delivery, Poly(dl-lactide-co-glycolide), Biomedical Engineering
Abstract

A water-soluble anthracycline antibiotic drug (daunorubicin, DNR) was loaded into oxidized porous silicon (pSiO2) microparticles and then encapsulated with a layer of polymer (poly lactide-co-glycolide, PLGA) to investigate their synergistic effects in control of DNR release. Similarly fabricated PLGA-DNR microspheres without pSiO2, and pSiO2 microparticles without PLGA were used as control particles. The composite microparticles synthesized by a solid-in-oil-in-water emulsion method have mean diameters of 52.33±16.37μm for PLGA-pSiO2_21/40-DNR and the mean diameter of 49.31±8.87μm for PLGA-pSiO2_6/20-DNR. The mean size, 26.00±8μm, of PLGA-DNR was significantly smaller, compared with the other two (P

Published
2014

26. Suppression of NLRP3/Caspase-1/GSDMD Mediated Corneal Epithelium Pyroptosis Using Melatonin-Loaded Liposomes to Inhibit Benzalkonium Chloride-Induced Dry Eye Disease

Author

Lou,Qi, Pan,Lu, Xiang,Shengjin, Li,Yueting, Jin,Jiahui, Tan,Jingyang, Huang,Baoshan, Nan,Kaihui, Lin,Sen, Lou,Qi, Pan,Lu, Xiang,Shengjin, Li,Yueting, Jin,Jiahui, Tan,Jingyang, Huang,Baoshan, Nan,Kaihui, and Lin,Sen

Abstract

Qi Lou,1,* Lu Pan,1,* Shengjin Xiang,1,2,* Yueting Li,1 Jiahui Jin,1 Jingyang Tan,1 Baoshan Huang,1,2 Kaihui Nan,1,2 Sen Lin1,2 1National Engineering Research Center of Ophthalmology and Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China; 2State Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kaihui Nan; Sen Lin, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China, Tel +86-577-88067962, Email lin_sen@wmu.edu.cn; nankh@l63.comIntroduction: Benzalkonium chloride (BAC) is widely employed as a preservative in eye drops, which will cause the death of corneal epithelial cells due to ROS production, DNA strand breakage, and mitochondrial dysfunction, resulting in dry eye disease (DED)-like changes in ocular surface tissues. In this study, Melatonin (MT) liposomes (TAT-MT-LIPs) designed by loading MT into TAT-modified liposomes have been developed, characterized, and used for inhibiting BAC-induced DED (BAC-DED).Methods: The TAT was chemically grafted onto the Mal-PEG2000-DSPE by Michael’s addition between the sulfhydryl group in TAT and the maleimide group in Mal-PEG2000-DSPE. TAT-MT-LIPs were prepared using film dispersion followed by the extrusion method and topically treated in rats once a day. BAC-DED was induced in rats by topical administration with 0.2% BAC twice daily. Defects, edema, and inflammation of the corneas, as well as IOP, were examined. Histologic analyses of corneas were performed to assess the change of mitochondrial DNA oxidation and NLRP3/Caspase-1/GSDMD signaling transduction.Results: After topical administration, TAT-MT-LIPs significantly alleviated DED-clinical symptoms of experim

Published
2023

32. Fabrication of Nonfouling, Bactericidal, and Bacteria Corpse Release Multifunctional Surface Through Surface-Initiated RAFT Polymerization [Corrigendum]

Author

Wang,Bailiang, Ye,Zi, Tang,Yihong, Han,Yuemei, Lin,Quankui, Liu,Huihua, Chen,Hao, and Nan,Kaihui

Subjects
Biomaterials, immune system diseases, International Journal of Nanomedicine, Organic Chemistry, Drug Discovery, Biophysics, Pharmaceutical Science, Bioengineering, General Medicine
Abstract

Wang B, Liu H, Sun L, et al. In J Nanomedicine. 2017;12:111–125. The authors have informed the journal that the scales bars in Figure 6, Figure 7 and Figure 11 were missed and the images in Figure 6E and 7E were mistakenly duplicated. It was also found the images selected to represent Figures 7A, 7D, 8A, 8B, 8C, 11B and 11C were selected from the wrong samples. New representative images have been selected from the original data to replace the original images used and scale bars have been added to Figure 6, Figure 7 and Figure 11. This correction does not change any description, results or conclusions of the original paper. The authors apologize for any confusion this may have caused. The corrected versions are shown in Download Article. Figure 6 Fluorescent microscopy images of live/dead staining of S. aureus. Notes: (A) Pristine PDMS, (B) p (DMAEMA+), (C) p (DMAEMA+-co-0.10 MPc), (D) p (DMAEMA+-co-0.25 MPC), and (E) p (DMAEMA+-co-0.50 MPC)-modified PDMS at 24 hours. The green color indicates live bacteria, and the red color indicates dead bacteria, under fluorescence microscopy (the magnification is 10×). (F) Adherence of the live/dead bacteria cell density on the surfaces. Figure 7 Fluorescent microscopy images of live/dead staining of S. aureus. Notes: (A) Pristine PDMS, (B) p (DMAEMA+), (C) p (DMAEMA+-co-0.10 MPc), (D) p (DMAEMA+-co-0.25 MPC), and (E) p (DMAEMA+-co-0.50 MPC)-modified PDMS at 72 hours. The green color indicates live bacteria, and the red color indicates dead bacteria, under fluorescence microscopy (the magnification is 10×). (F) Adherence of the live/dead bacteria cell density on the surfaces. Figure 8 SEM images. Notes: (A) Pristine PDMS, (B) p (DMAEMA+), (C) p (DMAEMA+-co-0.10 MPc), (D) p (DMAEMA+-co-0.25 MPC), and (E) p (DMAEMA+-co-0.50 MPC)-modified PDMS after exposure to waterborne S. aureus. (F) Adherence of the bacteria cell density on the surfaces. Figure 11 Growth and morphology of HLECs stained with FDA after 24 hours of incubation on various surfaces. Notes: (A) Pristine PDMS, (B) p (DMAEMA+), (C) p (DMAEMA+-co-0.10 MPc), (D) p (DMAEMA+-co-0.25 MPC), and (E) p (DMAEMA+-co-0.50 MPC)-modified PDMS and (F) adherence of the HLECs density on the surfaces. the magnification is 10×. Read the original article

Published
2022
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39. Synergistic Effect of Combined Sub-Tenon Triamcinolone and Intravitreal Anti-VEGF Therapy for Uveitic Macular Edema

Author

Lin,Dan, Hu,Jiajiang, Wu,Ke, Feng,Kemi, Zhao,Xia, Lu,Qingqing, Ren,Mingxue, Cao,Junlin, Liu,Ruru, Dai,Mali, Nan,Kaihui, Wang,Yuqin, Lin,Dan, Hu,Jiajiang, Wu,Ke, Feng,Kemi, Zhao,Xia, Lu,Qingqing, Ren,Mingxue, Cao,Junlin, Liu,Ruru, Dai,Mali, Nan,Kaihui, and Wang,Yuqin

Abstract

Dan Lin,1,&ast; Jiajiang Hu,2,&ast; Ke Wu,1 Kemi Feng,1 Xia Zhao,1 Qingqing Lu,3 Mingxue Ren,1 Junlin Cao,1 Ruru Liu,1 Mali Dai,1 Kaihui Nan,1 Yuqin Wang1 1The Eye Hospital, School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Ophthalmology, Shaoxing Central Hospital, Shaoxing, People’s Republic of China; 3Department of Ophthalmology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kaihui Nan; Yuqin Wang, The Eye Hospital, School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China, Email nankh@163.com; yqwang57@163.comPurpose: To investigate effects of intravitreal anti-VEGF in combination therapy with sub-Tenon triamcinolone acetonide (STA) injection for uveitic macular edema (UME).Design: A single-center, retrospective cohort study.Methods: The medical records were obtained for 65 eyes of 65 patients with UME. Of which, 32 eyes received combined anti-VEGF with STA injection, and 33 eyes received 40 mg of STA injection alone. The primary outcome was the reduction of central macular thickness (CMT) measured with optical coherence tomography (OCT). Resolution rate of clinical UME and changes of best corrected visual acuity (BCVA) over 24 weeks were secondary outcomes.Results: There was a significantly greater reduction of CMT with the combination treatment than with STA alone at 1-week (β = − 157.9, P < 0.001) and 1-month (β = − 53.1, P = 0.019) after injection. The cumulative incidence of macular edema resolution of all eyes was 87.7%, with 90.6% (29/32) in the combined group and 84.8% (28/33) in the STA group, respectively. More incidence of UME resolution was observed in the combined group than the STA group after 1 week (71.9% vs 15.2%, P < 0.001) and 4 weeks (84.4% vs 54.5%, P = 0.009), res

Published
2022

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