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PURPOSE: Dry eye disease (DED) is a prevalent ocular surface disease that is conventionally characterized by tear film hyperosmolarity and instability. This review presents a summarized classification of DED, followed by a comprehensive discussion of the most recent topical and systemic medications and clinical recommendations for selecting the most appropriate option for each patient. METHODS: An extensive literature search was conducted on electronic databases, such as PubMed, Scopus, and Web of Science, using keywords including "dry eye syndrome," "ocular surface disease," "medical management," "artificial tears," "topical immunomodulators," and "meibomian gland dysfunction." RESULTS: The underlying reasons for DED can range from insufficient aqueous tear production to increased tear evaporation. Recent literature has provided a more in-depth understanding of the pathophysiology of DED by examining the tear film's lipid, aqueous, and mucin layers. However, despite these advancements, medical management of patients with symptomatic DED has not fully reflected this modernized knowledge of its pathophysiology. CONCLUSION: To develop a rationalized strategy for treating DED, it is crucial to have updated knowledge of therapeutic options, their mechanisms of actions, and indications based on the DED type and underlying causes.
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Síndromes do Olho Seco , Disfunção da Glândula Tarsal , Humanos , Síndromes do Olho Seco/tratamento farmacológico , Síndromes do Olho Seco/etiologia , Lágrimas/fisiologia , Disfunção da Glândula Tarsal/complicaçõesRESUMO
Nanostructured fluorescent particles derived from natural molecules were prepared by a green synthesis technique employing a microwave method. The precursors citric acid (CA) and cysteine (Cys) were used in the preparation of S- and N-doped Cys carbon dots (Cys CDs). Synthesis was completed in 3 min. The graphitic structure revealed by XRD analysis of Cys CDs dots had good water dispersity, with diameters in the range of 2-20 nm determined by TEM analysis. The isoelectric point of the S, N-doped CDs was pH value for 5.2. The prepared Cys CDs displayed excellent fluorescence intensity with a high quantum yield of 75.6 ± 2.1%. Strong antimicrobial capability of Cys CDs was observed with 12.5 mg/mL minimum bactericidal concentration (MBC) against gram-positive and gram-negative bacteria with the highest antimicrobial activity obtained against Staphylococcus aureus. Furthermore, Cys CDs provided total biofilm eradication and inhibition abilities against Pseudomonas aeruginosa at 25 mg/mL concentration. Cys CDs are promising antioxidant materials with 1.3 ± 0.1 µmol Trolox equivalent/g antioxidant capacity. Finally, Cys CDs were also shown to inhibit the acetylcholinesterase (AChE) enzyme, which is used in the treatment of Alzheimer's disease, even at the low concentration of 100 µg/mL.
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Antibacterianos/farmacologia , Antioxidantes/farmacologia , Inibidores da Colinesterase/farmacologia , Ácido Cítrico/farmacologia , Cisteína/farmacologia , Corantes Fluorescentes/farmacologia , Acetilcolinesterase/metabolismo , Antibacterianos/síntese química , Antibacterianos/química , Antioxidantes/síntese química , Antioxidantes/química , Benzotiazóis/antagonistas & inibidores , Biofilmes/efeitos dos fármacos , Carbono/química , Carbono/farmacologia , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Ácido Cítrico/química , Cisteína/química , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Humanos , Pseudomonas aeruginosa/efeitos dos fármacos , Pontos Quânticos/química , Staphylococcus aureus/efeitos dos fármacos , Ácidos Sulfônicos/antagonistas & inibidoresRESUMO
Glycerol (Gly) is a well-known, FDA-approved molecule posing three hydroxyl groups. Since Gly is biocompatible, here, it was aimed to prepare poly(Glycerol) (p(Gly)) particles directly for the first time for the delivery of therapeutic agents. Micrometer-sized particles of p(Gly) were successfully synthesized via the micro-emulsion method with an average size of 14.5 ± 5.6 µm. P(Gly) microparticles up to 1.0 g/mL concentrations were found biocompatible with 85 ± 1% cell viability against L929 fibroblasts. Moreover, p(Gly) microparticles were tested for hemocompatibility, and it was found that up to 1.0 mg/mL concentrations the particles were non-hemolytic with 0.4 ± 0.1% hemolysis ratios. In addition, the blood compatibility index values of the prepared p(Gly) particles were found as 95 ± 2%, indicating that these microparticles are both bio- and hemocompatible. Furthermore, Quercetin (QC) flavonoid, which possessed high antioxidant properties, was loaded into p(Gly) microparticles to demonstrate drug-carrying properties of the particles with improved bioavailability, non-toxicity, and high biocompatibility. The results of this study evidently revealed that p(Gly) particles can be directly prepared from a cost-effective and easily accessible glycerol molecule and the prepared particles exhibited good biocompatibility, hemocompatibility, and non-toxicity. Therefore, p(Gly) particles were found as promising vehicles for drug delivery systems in terms of their higher loading and release capability as well as for sustained long term release profiles.
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Chondroitin sulfate (CS), a well-known glycosaminoglycan, was physically crosslinked with Fe(III), Gd(III), Zn(II), and Cu(II) ions to obtain CS-Fe(III), CS-Gd(III), CS-Zn(II), and CS-Cu(II) polymeric particles for multipurpose biological applications. The CS-metal ion-containing particles in the micrometer to a few hundred nanometer size range are injectable materials for intravenous administration. The CS-metal ion-containing particles are safe biomaterials for biological applications because of their perfect blood compatibility and no significant cytotoxicity on L929 fibroblast cells up to a 10 mg/mL concentration. Furthermore, CS-Zn(II) and CS-Cu(II) particles show excellent antibacterial susceptibility, with 2.5-5.0 mg/mL minimum inhibition concentration (MIC) values against Escherichia coli and Staphylococcus aureus. Moreover, the in vitro contrast enhancement abilities of aqueous CS-metal ion particle suspensions in magnetic resonance imaging (MRI) were determined by obtaining T1- and T2-weighted MR images using a 0.5 Tesla MRI scanner and by calculating the water proton relaxivities. Therefore, these CS-Fe(III), CS-Gd(III), CS-Zn(II), and CS-Cu(II) particles have significant potential as antibacterial additive materials and MRI contrast enhancement agents with less toxicity.
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Photo-activatable antipathogenic carbon dots (CDs) were prepared by carbonization of citric acid and arginine (Arg) via 3 min microwave treatment for use in the eradication of common microorganisms. Nitrogen-doped Arg CDs were spherical in shape with a size range of 0.5 to 5 nm. The Arg CDs were modified with fluorescent dyes, such as fluorescein sodium salt (FSS, as Arg-FSS) and riboflavin (RBF, as Arg-RBF), to improve antimicrobial potency by enhancing their application in photodynamic therapy. The modified Arg CDs afforded fluorescence emission properties at 520 nm in the green region in addition to excellent blue fluorescence intensity at 420 nm under 345 nm excitation upon their FSS and RBF conjugation, respectively. Although the cytotoxicity of Arg CDs was decreased for Arg-RBF CDs to 91.2 ± 0.7% cell viability for fibroblasts, the Arg-based CDs could be safely used for intravenous applications at 1000 µg/mL concentration. The Arg CDs showed broad-spectrum antimicrobial activity against common pathogens and the minimum inhibitory concentration of Arg CDs was almost two-fold decreased for the modified forms without UV light. However, faster and more effective antibacterial activity was determined for photosensitive Arg-RBF CDs, with total bacterial eradication upon UV-A light exposure for 30 min.
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Carboxymethyl chitosan (CMCh) is a unique polysaccharide with functional groups that can develop positive and negative charges due to the abundant numbers of amine and carboxylic acid groups. CMCh is widely used in different areas due to its excellent biocompatibility, biodegradability, water solubility, and chelating ability. CMCh microgels were synthesized in a microemulsion environment using divinyl sulfone (DVS) as a crosslinking agent. CMCh microgel with tailored size and zeta potential values were obtained in a single stem by crosslinking CMCh in a water-in-oil environment. The spherical microgel structure is confirmed by SEM analysis. The sizes of CMCh microgels varied from one micrometer to tens of micrometers. The isoelectric point of CMCh microgels was determined as pH 4.4. Biocompatibility of CMCh microgels was verified on L929 fibroblasts with 96.5 ± 1.5% cell viability at 1 mg/mL concentration. The drug-carrying abilities of CMCh microgels were evaluated by loading Vancomycin (Van) antibiotic as a model drug. Furthermore, the antibacterial activity efficiency of Van-loaded CMCh microgels (Van@CMCh) was investigated. The MIC values of the released drug from Van@CMCh microgels were found to be 68.6 and 7.95 µg/mL against E. coli and S. aureus, respectively, at 24 h contact time. Disk diffusion tests confirmed that Van@CMCh microgels, especially for Gram-positive (S. aureus) bacteria, revealed long-lasting inhibitory effects on bacteria growth up to 72 h.
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Cyclodextrins (CDs) are natural cyclic oligosaccharides with a relatively hydrophobic cavity and a hydrophilic outer surface. In this study, alpha (α-), beta (ß-) and gamma (γ-) CD particles were prepared by directly using α-, ß-, and γ-CDs as monomeric units and divinyl sulfone (DVS) as a crosslinker in a single-step via reverse micelle microemulsion crosslinking technique. Particles of p(α-CD), p(ß-CD), and p(γ-CD) were perfectly spherical in sub- 10 µm size ranges. The prepared p(CD) particles at 1.0 mg/mL concentrations were found biocompatible with > 95 % cell viability against L929 fibroblasts. Furthermore, p(α-CD) and p(ß-CD) particles were found non-hemolytic with < 2 % hemolysis ratios, whereas p(γ-CD) particles were found to be slightly hemolytic with its 2.1 ± 0.4 % hemolysis ratio at 1.0 mg/mL concentration. Furthermore, a toxic compound, Bisphenol A (BPA) and a highly antioxidant polyphenol, curcumin (CUR) complexation with α-, ß-, and γ-CD molecules was investigated via Electrospray-Ion Mobility-Mass Spectrometry (ESI-IM-MS) and tandem mass spectrometry (MS/MS) analysis. It was determined that the most stable noncovalent complex was in the case of ß-CD, but the complex stoichiometry was changed by the hydrophobic nature of the guest molecules. In addition, BPA and CUR were separately loaded into prepared p(CD) particles as active agents. The drug loading and release studies showed that p(CD) particles possess governable loading and releasing profiles.
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Curcumina , Ciclodextrinas , Humanos , Disponibilidade Biológica , Ciclodextrinas/farmacologia , Hemólise , Espectrometria de Massas em Tandem , Sistemas de Liberação de Medicamentos , Curcumina/farmacologiaRESUMO
Glycol chitosan (GC) is a chitosan (CH) derivative with improved water solubility with regards to CH which affords significant solubility advantages. In this study, microgels of GC as p(GC) were synthesized by a microemulsion technique at various crosslinking ratios e.g., 5%, 10%, 50%, 75%, and 150% based on the repeating unit of GC using divinyl sulfone (DVS) as a crosslinker. The prepared p(GC) microgels were tested for blood compatibility and it was found that p(GC) microgels at 1.0 mg/mL concentration possessed a 1.15 ± 0.1% hemolysis ratio and 89 ± 5% blood clotting index value confirming their hemocompatibility. In addition, p(GC) microgels were found biocompatible with 75.5 ± 5% cell viability against L929 fibroblasts even at a 2.0 mg/mL concentration. By loading and releasing tannic acid (TA) (a polyphenolic compound with high antioxidant activity) as an active agent, p(GC) microgels' possible drug delivery device application was examined. The TA loading amount of p(GC) microgels was determined as 323.89 mg/g, and TA releases from TA loaded microgels (TA@p(GC)) were found to be linear within 9 h and a total amount of TA released was determined as 42.56 ± 2 mg/g within 57 h. According to the Trolox equivalent antioxidant capacity (TEAC) test, 400 µL of the sample added to the ABTS+ solution inhibited 68.5 ± 1.7% of the radicals. On the other hand, the total phenol content (FC) test revealed that 2000 µg/mL of TA@p(GC) microgels resulted in 27.5 ± 9.5 mg/mL GA eq antioxidant properties.
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Hyaluronic acid/mannitol (HA/MN)-based particles were designed as mitomycin c (MMC) delivery vehicles through the crosslinking of 1:0, 3:1, 1:3, and 0:1 mole ratios of HA/MN to investigate their potential use in bladder cancer therapy. The HA/MN-MMC particles prepared by the microemulsion crosslinking method were of 0.5-10 µm size with a zeta potential value of -36.7 mV. The MMC carrier potential of the HA/MN-MMC particles was investigated by changing HA/MN ratios in the particle structure. The MMC loading capacity of neat HA particles was 5.3 ± 1.1 mg/g, whereas HA/MN (1:3) particles could be loaded with about three times more drug, for example, 18.4 ± 0.8 mg/g. The kinetic of MMC drug delivery from the HA/MN-MMC particles were tested in vitro in bladder cancer conditions for example, pH 4.5, 6, and 7.4. The HA-MMC particles released approximately 70% of the loaded drug in 300 h, while 43% of the loaded drug was released from the HA/MN-MMC particles within 600 h under physiological conditions, pH 7.4, 37 °C. The cytotoxicity of HA-based particles on healthy L929 fibroblast cells and HTB-9 human bladder cancer cells was investigated in vitro via MTT tests. Bare MMC inhibited about 90% of L929 fibroblast cells even at 100 µg/mL, but the cell viabilities in the presence of HA-MMC and HA/MN-MMC particles were 85 ± 5 and 109 ± 7% at 1000 µg/mL, respectively. The HA/MN-MMC (1:3) particles at 1000 µg/mL were found capable of destroying half of HTB-9 human bladder cancer cells within 24 h. Interestingly, the same particles at 50 µg/mL destroyed almost all the cancer cells with 8 ± 5% cell viability in 72 h of incubation time. The designed HA/MN-MMC (1:3) particles were found to afford a chemotherapeutic effect on the tumor cancers while reducing the toxicity of MMC against L929 fibroblast cells.
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Mitomicina , Neoplasias da Bexiga Urinária , Humanos , Mitomicina/farmacologia , Ácido Hialurônico/uso terapêutico , Manitol/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Polímeros/uso terapêutico , Excipientes/uso terapêuticoRESUMO
Antifungal drug-loaded hyaluronic acid (HA) microgels using conjugation and encapsulation drug-loading techniques were utilized in the treatment of fungal keratitis. Natamycin (NAT) and amphotericin B (AMB) drugs were chemically linked to HA microgels by employing a chemical coupling agent to obtain conjugated (C-) HA:NAT and HA:AMB microgels. Also, these drugs were loaded into the HA microgel network during HA microgel preparation to attain encapsulated (E-) HA:NAT and HA:AMB microgels. The conjugation of drug molecules was confirmed by FT-IR spectra of bare and drug-loaded HA microgels. It was determined that the AMB loading amount was about 4-fold higher for E-HA:AMB in comparison to C-HA:AMB microgels. Furthermore, the antifungal activity of drug conjugated and encapsulated HA:NAT and HA:AMB microgels was tested on Fusarium sp. and compared with the effect of bare drug molecules as control for up to 15 days of incubation time by means of the disc diffusion technique. The antifungal activity of 200 µL at 20 mg/mL concentration of C-HA:NAT and C-HA:AMB microgels was not found to effectively inhibit Fusarium sp. growth after 1 day of incubation, whereas the same concentration of E-HA:NAT and E-HA:AMB microgels totally killed Fusarium sp. for up to 15 days. These E-HA:NAT and E-HA:AMB microgels show no cytotoxicity on the L929 fibroblast cells up to 1000 µg/mL concentration, whereas the free drug molecules destroy the cells even at 100 µg/mL concentration.
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Úlcera da Córnea , Infecções Oculares Fúngicas , Microgéis , Anfotericina B/farmacologia , Antifúngicos/farmacologia , Úlcera da Córnea/tratamento farmacológico , Infecções Oculares Fúngicas/tratamento farmacológico , Humanos , Ácido Hialurônico/farmacologia , Natamicina/farmacologia , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Non-degradable, slightly degradable, and completely degradable micro/nanoparticles derived from chondroitin sulfate (CS) were synthesized through crosslinking reactions at 50%, 40%, and 20% mole ratios, respectively. The CS particles with a 20% crosslinking ratio show total degradation within 48 h, whereas 50% CS particles were highly stable for up to 240 h with only 7.0 ± 2.8% weight loss in physiological conditions (pH 7.4, 37 °C). Tobramycin and amikacin antibiotics were encapsulated into non-degradable CS particles with high loading at 250 g/mg for the treatment of corneal bacterial ulcers. The highest release capacity of 92 ± 2% was obtained for CS-Amikacin particles with sustainable and long-term release profiles. The antibacterial effects of CS particles loaded with 2.5 mg of antibiotic continued to render a prolonged release time of 240 h with 24 ± 2 mm inhibition zones against Pseudomonas aeruginosa. Furthermore, as a carrier, CS particles significantly improved the compatibility of the antibiotics even at high particle concentrations of 1000 g/mL with a minimum of 71 ± 7% fibroblast cell viability. In summary, the sustainable delivery of antibiotics and long-term treatment of bacterial keratitis were shown to be afforded by the design of tunable degradation ability of CS particles with improved biocompatibility for the encapsulated drugs.
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Hyaluronic acid (HA) was crosslinked with Gd(III) and Fe(III) ions rendering physically crosslinked HA-metal(III) microgels as magnetic resonance imaging (MRI) enhancing contrast agents. These HA-Gd(III) and HA-Fe(III) microgels are injectable with size range, 50-5000 nm in water. The same isoelectric point, pH 1.2 ± 0.1, was measured for both microgels. HA-Gd(III) and HA-Fe(III) microgels are hemo-compatible biomaterials and can be safely used in intravascular applications up to 1000 µg/mL concentration. Furthermore, no significant toxicity was attained as 95 ± 8 and 81 ± 2% cell viability on L929 fibroblast cells at 100 µg/mL of HA-Gd(III) and HA-Fe(III) microgels were measured. Moreover, HA-Gd(III) microgels were found to afford significant contrast improvement capability in MRI with proton relaxivity, r1 = 2.11 mM-1 s-1, comparable with the values reported for Gd(III) labeled functionalized HA gel systems and commercial Gd based contrast agents.
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Fungal corneal ulcers are an uncommon, yet challenging, cause of vision loss. In the United States, geographic location appears to dictate not only the incidence of fungal ulcers, but also the fungal genera most encountered. These patterns of infection can be linked to environmental factors and individual characteristics of fungal organisms. Successful management of fungal ulcers is dependent on an early diagnosis. New diagnostic modalities like confocal microscopy and polymerase chain reaction are being increasingly used to detect and identify infectious organisms. Several novel therapies, including crosslinking and light therapy, are currently being tested as alternatives to conventional antifungal medications. We explore the biology of Candida, Fusarium, and Aspergillus, the three most common genera of fungi causing corneal ulcers in the United States and discuss current treatment regimens for the management of fungal keratitis.
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Úlcera da Córnea , Infecções Oculares Fúngicas , Ceratite , Antifúngicos/uso terapêutico , Úlcera da Córnea/tratamento farmacológico , Úlcera da Córnea/terapia , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/terapia , Humanos , Ceratite/tratamento farmacológico , Ceratite/terapia , Úlcera/tratamento farmacológicoRESUMO
PURPOSE: To compare operative outcomes of patients after canaloplasty and trabeculectomy through 12 months' follow-up. DESIGN: Retrospective, nonrandomized, comparative case series. PARTICIPANTS: We included 33 eyes of 33 patients who underwent canaloplasty and 46 eyes of 46 patients who underwent trabeculectomy with 12 months' of postoperative follow-up. METHODS: Patients with open-angle glaucoma who underwent either canaloplasty or trabeculectomy with mitomycin C to control the intraocular pressure (IOP) between January 2007 and December 2008 were included. All surgeries were performed by a single surgeon (R.S.A.). MAIN OUTCOME MEASURES: Change in IOP, visual acuity (VA), postoperative medications, failure based on IOP (>18 or <4 mmHg at 1 year) or second operative procedure (any eye requiring reoperation) and complication rates at 12 months. RESULTS: There were no differences in demographics, previous surgery, or preoperative and postoperative VA between the groups. The mean percentage reduction in IOP from preoperative values at 12 months after surgery was 32% (± 22%) for the canaloplasty group compared with 43% (± 28%) for the trabeculectomy group (P = 0.072, Student t test). The median reduction in the number of medications at 12 months' follow-up was 3 in the trabeculectomy group and 2 in the canaloplasty group (P = 0.064). A higher percentage of patients treated with canaloplasty than trabeculectomy (36% vs. 20%) required postoperative medications, although this did not attain significance (P = 0.12). Failure based on IOP (IOP >18 or <4 mmHg at 12 months) was 12.1% (4/33 patients) for the canaloplasty group and 4.3% (2/46 patients) for the trabeculectomy group (P = 0.23, Fisher exact test). There was no difference in surgical failure rates between the canaloplasty (n = 5; 15%) and trabeculectomy (n = 5; 11%) groups (P = 0.74). CONCLUSIONS: Canaloplasty and trabeculectomy both achieved significant reduction in IOP at 12 months. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
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Cirurgia Filtrante/métodos , Glaucoma de Ângulo Aberto/cirurgia , Trabeculectomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Alquilantes/administração & dosagem , Terapia Combinada , Feminino , Seguimentos , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Estudos Retrospectivos , Resultado do Tratamento , Acuidade Visual/fisiologiaRESUMO
PURPOSE: To measure variations in diameter and location of Schlemm's canal in vivo by ultrasound biomicroscopy. DESIGN: Prospective, single-institution, consecutive case series. PARTICIPANTS: Ninety-four patients with and without glaucoma. METHODS: Under topical anesthesia, an 80-MHz iUltrasound probe (iScience Interventional, Inc., Menlo Park, CA) placed at the 12-o'clock position was used to measure the canal's diameter and its distance from both the anatomic limbus (corneoscleral junction) and the angle (the base of the canal and the angle of iris insertion). MAIN OUTCOME MEASURES: Diameter and location of the canal were measured relative to gender, age, intraocular pressure, race, diagnosis, previous glaucoma surgery, pachymetry, refraction, lens type, axial length, and keratometry. RESULTS: The average canal diameter was 121 microm (+/-45 microm). The canal diameter in hyperopes was larger than the canal diameter in myopes (180+/-69 microm vs. 122+/-45 microm; P<0.001). The diameter of Schlemm's canal was smaller in patients with previous glaucoma surgery compared with patients without glaucoma surgery (98+/-20 microm vs. 125+/-4 microm; P<0.01). The mean distance between the angle and Schlemm's canal was found to be smaller in hyperopes than in myopes (281 vs. 335 microm; P = 0.03). The location of the canal in black patients compared with white patients was found to be more posterior from the limbus (659+/-92 microm vs. 624+/-73 microm; P = 0.05). Similarly, canal location in patients with corneal thickness of more than 555 microm was found to be more posterior to the limbus (702 vs. 625 microm; P<0.01) compared with those with thinner corneas. CONCLUSIONS: When measured in vivo with ultrasound biomicroscopy, Schlemm's canal diameter was significantly smaller (121 microm) than demonstrated in previous histopathologic studies.
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Limbo da Córnea/diagnóstico por imagem , Microscopia Acústica , Adulto , Idoso , Idoso de 80 Anos ou mais , Antropometria , Humor Aquoso/metabolismo , Feminino , Glaucoma/diagnóstico por imagem , Humanos , Hiperopia/diagnóstico por imagem , Pressão Intraocular , Limbo da Córnea/metabolismo , Masculino , Pessoa de Meia-Idade , Miopia/diagnóstico por imagem , Estudos Prospectivos , Adulto JovemRESUMO
Here, the aim was to design and use a long-lasting antibiotic release system for prevention of postoperative infections in ophthalmic surgery. Ciprofloxacin and vancomycin-conjugated hyaluronic acid (HA) particles were prepared as drug carriers for sustained release of antibiotics. The antimicrobial effects of the released drugs were determined by disc-diffusion and macro-dilution tests at different times up to 2 weeks. Slow degradable HA particles were obtained with 35.2 wt% degradation within 21 days. The drug loading amount was increased by employing two sequential chemical linking (conjugation, 2C) and one physical absorption loading (A) procedures (2C + A processes) from 148 ± 8 to 355 ± 11 mg/g HA particles for vancomycin. The amounts of vancomycin and ciprofloxacin that were released linearly was estimated as 64.35 ± 7.35 and 25.00 ± 0.68 mg/g, respectively, from drug-conjugated HA particles in 100 h. Antimicrobial studies revealed that antibiotic-conjugated HA particles could inhibit the growth of microorganisms from 1 h to 1 week. The MBC values were measured as 0.25, 4.0, and 0.25 mg/mL against Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis, respectively, after 72 h incubation time. Cytotoxicity studies showed no difference between fibroblast growth or corneal thickness after 5 days with or without HA-antibiotic particles. The drug release studies and antimicrobial activity of antibiotic-loaded HA particles with time against various bacteria further revealed that HA particles are very effective in preventing bacterial infections. Likewise, cytotoxicity studies suggest that these particles pose no toxicity to eukaryotic cells, including corneal endothelium.
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Antibacterianos/administração & dosagem , Ciprofloxacina/administração & dosagem , Portadores de Fármacos , Infecções Oculares Bacterianas/prevenção & controle , Ácido Hialurônico/química , Vancomicina/administração & dosagem , Administração Oftálmica , Antibacterianos/química , Antibacterianos/toxicidade , Bacillus subtilis/efeitos dos fármacos , Bacillus subtilis/crescimento & desenvolvimento , Ciprofloxacina/química , Ciprofloxacina/toxicidade , Preparações de Ação Retardada , Composição de Medicamentos , Liberação Controlada de Fármacos , Infecções Oculares Bacterianas/microbiologia , Humanos , Ácido Hialurônico/toxicidade , Cinética , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Solubilidade , Staphylococcus/efeitos dos fármacos , Staphylococcus/crescimento & desenvolvimento , Vancomicina/química , Vancomicina/toxicidadeRESUMO
Vision loss is a major complication in common ocular infections and diseases such as bacterial keratitis, age-related macular degeneration (AMD) and diabetic retinopathy (DR). The prevalence of such ophthalmic diseases represents an urgent need to develop safe, effective, and long-term treatments. Current therapies are riddled with drawbacks and limitations which calls for the exploration of alternative drug delivery mechanisms. Toxicity of the inorganic metals and metal oxides used for drug delivery raise safety concerns that are alleviated with the alternate use of, a natural and organic polymer which is both biocompatible and environmentally friendly. Carbon dots (CDs) represent a great potential in novel biomedical applications due to their tunable fluorescence, biocompatibility, and ability to be conjugated with diverse therapeutic materials. There is a growing interest on the exploitation of these properties for drug delivery with enhanced bio-imaging. However, there are limited reports of CD applications for ophthalmic indications. In this review, we focus on the CD potential and the development of translational therapies for ophthalmic diseases. The current review presents better understanding of fabrication of CDs and how it may be useful in delivering anti-bacterial agents, anti-VEGF molecules as well as imaging for ophthalmic applications.
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A 51-year-old man presented with acute iridocyclitis with no evidence of vitritis on B-scan that progressed to endogenous endophthalmitis. Systemic work-up revealed a large liver abscess. Urine, blood, liver abscess, and vitreous aspirate cultures all grew Klebsiella pneumoniae. The eye was enucleated secondary to severe pain from neovascular glaucoma and loss of vision.
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Endoftalmite/etiologia , Infecções Oculares Bacterianas/etiologia , Iridociclite/etiologia , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/isolamento & purificação , Abscesso Hepático/complicações , Diagnóstico Diferencial , Endoftalmite/diagnóstico , Endoftalmite/microbiologia , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/microbiologia , Humanos , Iridociclite/diagnóstico , Iridociclite/microbiologia , Infecções por Klebsiella/diagnóstico , Abscesso Hepático/diagnóstico , Abscesso Hepático/microbiologia , Masculino , Pessoa de Meia-IdadeRESUMO
HYPOTHESIS: Lactose (LAC) is a primary carbohydrate and energy source of milk has received intensive attention due to its' unique functional and nutritional properties. Many biological beneficences of LAC make it an appealing molecule to seek for designing functional interfaces. Therefore, crosslinked poly(lactose) (p(LAC)) microgel from lactose disaccharides for potential biomedical applications was pursued as biocolloids for the first time. EXPERIMENT: p(LAC) microgels prepared by chemical crosslinking with DiVinyl Sulfone (DVS) were chemically modified with ethylenediamine (EDA) to obtain amine-modified p(LAC) (p(LAC)-EDA) microgels to induce new functionalities and properties. Blood compatibilities of bare p(LAC)-EDA microgels were tested through hemolysis and blood clotting tests. Rosmarinic acid (RA) used as a model drug was loaded into p(LAC) and p(LAC)-EDA microgels to demonstrate their applicability to be used in drug loading and release applications. FINDINGS: A facile preparation of p(LAC) microgels with high yield, 90⯱â¯5% and 0.5-50 µm size range was accomplished via water-in-oil (w/o) microemulsion crosslinking method. Upon chemical modification, the isoelectric point (IEP) from pH 1.8 for p(LAC) microgels changed to pH 7.7 for p(LAC)-EDA microgels, and the blood compatibility studies revealed that both microgels can be considered as blood compatible up to 2â¯mg/mL concentration, and only slight decrease in blood clotting index (BCI) of p(LAC)-EDA microgels was observed. Rosmarinic Acid (RA) was demonstrated to be released up to 4â¯days in phosphate buffer saline (PBS) with a linear release profile for p(LAC)-EDA microgels.
Assuntos
Reagentes de Ligações Cruzadas/química , Lactose/química , Microgéis/química , Polímeros/química , Pesquisa Biomédica , Reagentes de Ligações Cruzadas/síntese química , Lactose/síntese química , Estrutura Molecular , Tamanho da Partícula , Polímeros/síntese química , Propriedades de SuperfícieRESUMO
PURPOSE: To compare surgical outcomes of patients after phacoemulsification with goniosynechialysis (phaco/GSL) versus phaco with GSL and endocyclophotocoagulation (phaco/GSL/ECP) in patients with chronic angle closure glaucoma (CACG) through 12-month follow-up. METHODS: A retrospective, nonrandomized, comparative case series was performed. Patients with CACG who underwent phaco in combination with either GSL alone (group 1) or GSL with ECP with intracameral injection of kenalog (group 2) from 2011 to 2018 were included. Group 1 included 6 eyes of 6 patients and group 2 included 11 eyes of 10 patients. All surgeries were performed by a single surgeon (RSA). Primary outcome measures included changes in intraocular pressure (IOP), visual acuity (VA), failure based on IOP (>18 or <6 mmHg at 1 year), and secondary operative procedures and complication rates. Data were analyzed using a paired two-tailed T-test. RESULTS: The mean preoperative IOP decreased from 23.5 ± 11.2 to 14.2 ± 2.4 mmHg (P < 0.0073) in group 1 and 24.4 ± 8.2 to 14.5 ± 2.7 mmHg (P < 0.0001) in group 2. The mean % IOP reduction was 33.7% in group 1 and 34.2% in group 2. The mean improvement in VA (logMAR units) was 0.24 (P = 0.085) in group 1 and 0.13 (P = 0.657) in group 2. The mean number of topical meds decreased from 2.50 ± 1.76 to 1.80 ± 1.64 in group 1 (P = 0.513) and from 2.82 ± 1.25 to 1.17 ± 0.98 in group 2 (P = 0.014). CONCLUSION: Phaco/GSL and phaco/GSL/ECP both achieve a significant reduction in IOP without the complications associated with traditional glaucoma filtration surgeries.