Abstract:
PURPOSE:Current standard of care for neovascular eye diseases require repeated intravitreal bolus injections of anti-vascular endothelial growth factors (anti-VEGFs). The purpose of this study was to validate a degradable microsphere-thermoresponsive hydrogel drug delivery system (DDS) capable of releasing bioactive aflibercept in a controlled and extended manner for 6 months. MATERIALS AND METHODS:The DDS was fabricated by suspending aflibercept-loaded poly(lactic-co-glycolic acid) microspheres within a biodegradable poly(ethylene glycol)-co-(l-lactic acid) diacrylate/N-isopropylacrylamide (PEG-PLLA-DA/NIPAAm) thermoresponsive hydrogel. Encapsulation efficiency of DDSs and in vitro release profiles were characterized by iodine-125 radiolabeled aflibercept. The degradation of hydrogel was determined by dry weight changes. The cytotoxicity from degraded DDS byproducts was investigated by quantifying cell viability using LIVE/DEAD® assay. In addition, dot blot and enzyme-linked immunosorbent assay were used to determine the bioactivity of released drug. Finally, morphology of microspheres and hydrogel were investigated by cryo-scanning electron microscopy before and after thermal transformation. RESULTS:The microsphere-hydrogel DDS was capable of releasing bioactive aflibercept in a controlled and extended manner for 6 months. The amount and rate of aflibercept release can be controlled by both the cross-linker concentration and microspheres load amount. The initial burst (release within 24 h) was from 37.35 ± 4.92 to 74.56 ± 6.16 µg (2 and 3 mM hydrogel, each loaded with 10 and 20 mg/ml of microspheres, respectively), followed by controlled drug release of 0.07-0.15 µg/day. Higher PEG-PLLA-DA concentration (3 mM) degraded faster than the lower concentration (2 mM). No significant cytotoxicity from degraded DDS byproducts was found for all investigated time points. Bioactivity of released drug was maintained at therapeutic level over entire release period. CONCLUSIONS:The microsphere-hydrogel DDS is safe and can deliver bioactive aflibercept in a controlled manner. This may provide a significant advantage over current bolus injection therapies in the treatment of ocular neovascularization.
journal_name
Curr Eye Resjournal_title
Current eye researchauthors
Liu W,Lee BS,Mieler WF,Kang-Mieler JJdoi
10.1080/02713683.2018.1533983subject
Has Abstractpub_date
2019-03-01 00:00:00pages
264-274issue
3eissn
0271-3683issn
1460-2202journal_volume
44pub_type
杂志文章abstract:PURPOSE:To determine if the Schirmer I test (without anesthesia) cut-off value is a predictor of dry eye severity in a large Norwegian cohort of dry eye disease (DED) patients, which are grouped into six levels of tear production. METHODS:Patients (n = 1090) with DED of different etiologies received an extensive dry e...
journal_title:Current eye research
pub_type: 杂志文章
doi:10.1080/02713683.2018.1514055
更新日期:2018-12-01 00:00:00
abstract:PURPOSE:To investigate whether zeaxanthin, the predominant carotenoid pigment of the macular pigments in human retina, provides neuroprotection against retinal cell damage. METHODS:We used in vitro cultured retinal ganglion cells (RGCs), specifically RGC-5, an E1A virus-transformed rat cell line. Cell damage was induc...
journal_title:Current eye research
pub_type: 杂志文章
doi:10.1080/02713680902745408
更新日期:2009-04-01 00:00:00
abstract:PURPOSE:To optimize cultured human corneal endothelial cell (cHCEC) sheet transplantation technique for maintenance of cHCEC viability. MATERIALS AND METHODS:cHCEC sheets cultured on a collagen scaffold were covered with or without Viscoat® and exposed to humidified air in the incubator. cHCEC sheets with or without V...
journal_title:Current eye research
pub_type: 杂志文章
doi:10.3109/02713683.2015.1101774
更新日期:2016-09-01 00:00:00
abstract::The concentrations of hyaluronan (HA) and chondroitin sulfate (CS) in rabbit tears were determined using high performance liquid chromatography. The tears were taken from both normal eyes and eyes with a corneal epithelial defect. The concentration of CS was 7.61 times higher than that of HA in the tears of normal eye...
journal_title:Current eye research
pub_type: 杂志文章
doi:10.3109/02713689608997405
更新日期:1996-02-01 00:00:00
abstract::Glucocorticoid-induced ocular hypertension has been demonstrated in both animals and humans. It is possible that glucocorticoid-induced changes in trabecular meshwork (TM) cells are responsible for this hypertension. In order to elaborate further the effect of glucocorticoids on the trabecular meshwork, the ultrastruc...
journal_title:Current eye research
pub_type: 杂志文章
doi:10.3109/02713689309020383
更新日期:1993-09-01 00:00:00
abstract::Goggles that degrade the retinal image produce axial enlargement of the ocular globe and large myopic refractive errors. Many authors have assumed that visual image degradation itself leads to myopia. Hodos and co-authors have shown, however, that goggled eyes in chicks are considerably warmer than normal. Such temper...
journal_title:Current eye research
pub_type: 杂志文章
doi:10.3109/02713689308999467
更新日期:1993-03-01 00:00:00
abstract::Corneal acidosis has been shown to reduce corneal hydration control (CHC) as measured by the rate, expressed as the percent recovery per hour (PRPH), at which the thickness of the cornea decreases exponentially after an increased hydration load. Since the effect of pH on corneal function is of scientific interest and ...
journal_title:Current eye research
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.3109/02713689508999932
更新日期:1995-05-01 00:00:00
abstract:PURPOSE:The aim of this study was to investigate how glutathione reductase (GR) loses its activity during cataract formation and whether it is possible to revive it back to the normal levels. METHOD:In this study, endogenous as well as synthetic reducing systems (GSH, TTase, DTT, captopril) and alpha-crystallin at dif...
journal_title:Current eye research
pub_type: 杂志文章
doi:10.1080/02713680590953110
更新日期:2005-10-01 00:00:00
abstract::The reactions of lectins with dissociated and cultured epithelial cells from hyperplastic lenses of two unrelated chick strains, Hy-1 and Hy-2, characterised by hyperplasia of the lens epithelium, and lenses of a normal genotype (N) were investigated using four different lectins. Three methods of monitoring lectin-bin...
journal_title:Current eye research
pub_type: 杂志文章
doi:10.3109/02713688509000845
更新日期:1985-03-01 00:00:00
abstract:PURPOSE:Diabetic maculopathy (DM) treated with photocoagulation may subsequently progress to proliferative diabetic retinopathy (PDR). However, there is insufficient knowledge about the incidence and risk factors for the development of PDR in patients previously treated for DM. MATERIALS AND METHODS:Survival data was ...
journal_title:Current eye research
pub_type: 杂志文章
doi:10.1080/02713683.2020.1712729
更新日期:2020-08-01 00:00:00
abstract:PURPOSE:Retinoblastoma (RB) is the most common intraocular malignancy in children. Deregulation of several miRNAs has been identified in RB, suggesting a potential role in tumorigenesis. Recent evidence suggests that many dietary components like folate, retinoids and curcumin act as potential anticancer/antiproliferati...
journal_title:Current eye research
pub_type: 杂志文章
doi:10.3109/02713683.2011.647224
更新日期:2012-05-01 00:00:00
abstract::We examined jun-B gene expression in the rat retina after a focal retinal injury by in situ hybridization. 30 min after producing a penetrating retinal wound, the retina showed the expression of jun-B mRNA intensively in the inner nuclear layer (INL) and relatively sparsely in the ganglion cell layer. The double-label...
journal_title:Current eye research
pub_type: 杂志文章
doi:10.3109/02713689508998524
更新日期:1995-11-01 00:00:00
abstract:PURPOSE:The aim of this pilot study was to determine the presence of complement activation products in tears from pre- and postkeratoplasty eyes and the fellow eyes in order to investigate the activation of the classical and alternative pathways of the complement system in the early postkeratoplasty period. METHODS:Te...
journal_title:Current eye research
pub_type: 杂志文章
doi:10.1076/ceyr.24.2.99.8165
更新日期:2002-02-01 00:00:00
abstract:PURPOSE:To investigate the multifocal electroretinogram (mfERG) and subjective function in early age-related maculopathy (ARM). METHODS:Seventeen subjects with early ARM with visual acuity (VA) of 6/12 or better and 20 age-matched control subjects were examined. We assessed mfERGs, high and low contrast distance VA, n...
journal_title:Current eye research
pub_type: 杂志文章
doi:10.1080/02713680490516198
更新日期:2004-10-01 00:00:00
abstract::Purpose/Aim: To determine the associations among socioeconomic factors, delay in management, and high-risk histopathologic features in eyes primarily enucleated for retinoblastoma. Materials and Methods: A single-site survey was conducted from January 2016 through January 2018. Eyes primarily enucleated for unilateral...
journal_title:Current eye research
pub_type: 杂志文章
doi:10.1080/02713683.2019.1623898
更新日期:2019-10-01 00:00:00
abstract:PURPOSE:Frequent steroid drops represent a challenge in patient compliance. This study evaluated the safety and efficacy of 5 minute topical dexamethasone sodium phosphate-Visulex (DSP-Visulex) treatment regimen (two applications on the first week then weekly after) compared to daily prednisolone acetate 1% (PA) for no...
journal_title:Current eye research
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1080/02713683.2018.1540707
更新日期:2019-02-01 00:00:00
abstract:PURPOSE:Nitric oxide production can cause either apoptotic or necrotic cell death through oxidative stress. We aimed to investigate the nitrite oxide metabolites (NOx) and nitrite levels in the aqueous humor of rabbit eyes after different methods of corneal collagen cross-linking (CXL). MATERIALS AND METHODS:Twenty-fo...
journal_title:Current eye research
pub_type: 杂志文章
doi:10.3109/02713683.2016.1139726
更新日期:2016-12-01 00:00:00
abstract:PURPOSE:To determine whether environmental factors or bacterial viability affect the binding of two strains of P. aeruginosa to mouse cornea. METHODS:Scarified corneas were placed in organ culture and inoculated with P. aeruginosa cell suspensions containing either ATCC 19660 or PAO1 bacterial strains classed as cytot...
journal_title:Current eye research
pub_type: 杂志文章
doi:10.1076/ceyr.17.3.231.5226
更新日期:1998-03-01 00:00:00
abstract::Purpose: Notch signaling plays a vital role in the differentiation and proliferation of corneal epithelial cells from limbal stem cells. The temporal regulation of Notch signaling during this differentiation remains unknown. Hence, we investigated the importance of temporal activation/blockage of Notch signaling durin...
journal_title:Current eye research
pub_type: 杂志文章
doi:10.1080/02713683.2019.1673436
更新日期:2020-04-01 00:00:00
abstract:PURPOSE:Pseudoexfoliation (PXF) is a microfibrillopathy involving disordered elastogenesis. Abnormal extracellular matrix (ECM) production underlies the pathophysiology of PXF. The enzyme Lysyl oxidase (LOX) and its isoforms are known to cross-link the elastin and collagen. Though the etiopathogensis of PXF is not well...
journal_title:Current eye research
pub_type: 杂志文章
doi:10.3109/02713683.2015.1125505
更新日期:2016-10-01 00:00:00
abstract::The management of opportunistic infections is a significant problem in acquired immunodeficiency syndrome (AIDS) and the development of more effective chemotherapeutic agents is needed. We present the ocular manifestations of an AIDS-like disease in rhesus monkeys experimentally infected with simian immunodeficiency v...
journal_title:Current eye research
pub_type: 杂志文章
doi:10.3109/02713689008999571
更新日期:1990-08-01 00:00:00
abstract:PURPOSE:The aim of this study was to characterize swelling pressure-thickness, swelling pressure-hydration and hydration-thickness relations of porcine cornea. METHODS:Mechanical compression tests and free swelling experiments were performed on porcine cornea. A rheometer (DHR-2, TA Instruments) with a thermally contr...
journal_title:Current eye research
pub_type: 杂志文章
doi:10.3109/02713683.2013.809769
更新日期:2013-11-01 00:00:00
abstract::A model for endothelial transport is updated to include recent evidence. We discuss electrolyte movements based on a Na+-K+ ATPase, a Na+-H+ exchanger, a Na+-HCO3 coupler, a Cl- -HCO-3 exchanger, a K+-Cl-coupler, and K+ and anion channels. We discuss near-isotonic transport of fluid on the basis of recent findings of ...
journal_title:Current eye research
pub_type: 杂志文章
doi:10.3109/02713688509025148
更新日期:1985-04-01 00:00:00
abstract:PURPOSE:To compare the efficacy and tolerability of diclofenac and bromfenac ophthalmic solutions as adjunctive therapy after cataract surgery. MATERIALS AND METHODS:This prospective randomized controlled study included 130 patients who underwent cataract surgery. One hundred patients were randomized to receive postop...
journal_title:Current eye research
pub_type: 杂志文章,随机对照试验
doi:10.1080/02713683.2018.1501489
更新日期:2018-12-01 00:00:00
abstract::The content of rhodopsin in the eyes of 15 donors (30 eyes) was determined. Both retinal and pigment epithelial fractions were collected from each globe, extracted using 1% CTAB, and the rhodopsin difference spectrum of each fraction was obtained separately. The total amount of rhodopsin, obtained by summing the amoun...
journal_title:Current eye research
pub_type: 杂志文章
doi:10.3109/02713689009003477
更新日期:1990-12-01 00:00:00
abstract:PURPOSE:To synthesize and characterize hydrogels with viscoelastic properties comparable to those of the natural lens. METHODS:Hydrogels were synthesized in water by free-radical polymerization of the monomer poly(ethyleneglycol)-monomethacrylate. Three different molecular weights of poly(ethyleneglycol)-dimethacrylat...
journal_title:Current eye research
pub_type: 杂志文章
doi:10.1076/ceyr.22.5.384.5493
更新日期:2001-05-01 00:00:00
abstract:PURPOSE:To determine by immunohistochemistry the distribution of different nitric oxide synthases (NOS) isoforms in the porcine eye. METHODS:By light microscopy (immunofluorescence), porcine ocular tissues were investigated using monoclonal antibodies against neuronal NOS (nNOS; NOS I), endothelial NOS (ecNOS; NOS III...
journal_title:Current eye research
pub_type: 杂志文章
doi:10.1076/ceyr.18.5.375.5355
更新日期:1999-05-01 00:00:00
abstract:PURPOSE:To investigate the efficacy of intravitreal piperacillin/tazobactam (250 microg/0.1 ml) in the treatment of experimental Pseudomonas aeruginosa endophthalmitis in rabbits. MATERIALS AND METHODS:Twenty New Zealand White albino rabbits were used in this study. The rabbits were divided into two groups (10 rabbits...
journal_title:Current eye research
pub_type: 杂志文章
doi:10.1080/02713680490894180
更新日期:2005-01-01 00:00:00
abstract::VIP markedly stimulates intracellular cAMP accumulation in the human retinoblastoma Y-79 cell line. cAMP increased about 5-fold above the basal level with 10(-8)M VIP and reached a maximum level (about 70-fold increase) with 2 X 10(-6)M VIP. Glucagon at 6 X 10(-8)M significantly increased cAMP accumulation with a maxi...
journal_title:Current eye research
pub_type: 杂志文章
doi:10.3109/02713688408997218
更新日期:1984-02-01 00:00:00
abstract::Calcium permeability was significantly increased in lenses from rats 36 h following a single injection of a cataractogenic dose of sodium selenite (30 nmol/g body weight) and this permeability returned to control values by 72 h post-injection (PI). The greater Ca2+ permeability could be partially reversed by incubatin...
journal_title:Current eye research
pub_type: 杂志文章
doi:10.3109/02713689308999466
更新日期:1993-03-01 00:00:00