Pharmacokinetics of Curcumin Delivered by Nanoparticles and the Relationship with Antitumor Efficacy: A Systematic Review.

Curcumin is a polyphenolic compound, derived from Curcuma longa, and it has several pharmacological effects such as antioxidant, anti-inflammatory, and antitumor. Although it is a pleiotropic molecule, curcumin's free form, which is lipophilic, has low bioavailability and is rapidly metabolized, limiting its clinical use. With the advances in techniques for loading curcumin into nanostructures, it is possible to improve its bioavailability and extend its applications. In this review, we gather evidence about the comparison of the pharmacokinetics (biodistribution and bioavailability) between free curcumin (Cur) and nanostructured curcumin (Cur-NPs) and their respective relationships with antitumor efficacy. The search was performed in the following databases: Cochrane, LILACS, Embase, MEDLINE/Pubmed, Clinical Trials, BSV regional portal, ScienceDirect, Scopus, and Web of Science. The selected studies were based on studies that used High-Performance Liquid Chromatography (HPLC) as the pharmacokinetics evaluation method. Of the 345 studies initially pooled, 11 met the inclusion criteria and all included studies classified as high quality. In this search, a variety of nanoparticles used to deliver curcumin (polymeric, copolymeric, nanocrystals, nanovesicles, and nanosuspension) were found. Most Cur-NPs presented negative Zeta potential ranging from -25 mV to 12.7 mV, polydispersion index (PDI) ranging from 0.06 to 0.283, and hydrodynamic diameter ranging from 30.47 to 550.1 nm. Selected studies adopted mainly oral and intravenous administrations. In the pharmacokinetics analysis, samples of plasma, liver, tumor, lung, brain, kidney, and spleen were evaluated. The administration of curcumin, in nanoparticle systems, resulted in a higher level of curcumin in tumors compared to free curcumin, leading to an improved antitumor effect. Thus, the use of nanoparticles can be a promising alternative for curcumin delivery since this improves its bioavailability.

Descemet Membrane Detachment Due to Laser Application in Femtosecond Laser-Assisted Cataract Surgery: Incidence and Risk Factors.

PURPOSE: To assess the incidence and risk factors of Descemet membrane detachment due to laser application in femtosecond laser-assisted cataract surgery (FLACS). METHODS: In this retrospective case series, all patients who underwent FLACS with the LenSx system (Alcon Laboratories, Inc) were eligible to participate. The medical records were reviewed to collect data regarding potential risk factors related to Descemet membrane detachment, including patients' demographics, laser parameters, and ocular measurements. The eyes were separated into two groups based on the clinical diagnosis of Descemet membrane detachment as the femto-second laser was performing the corneal incisions. RESULTS: Five hundred ten eyes (304 patients) were included. Descemet membrane detachment occurred in 20 (3.9%) eyes of 16 (5.3%) patients. Four (1.3%) patients had a detachment in both eyes. In 16 (3.1%) eyes, the Descemet membrane detachment occurred in the secondary incision site. The eyes that had a detachment had a statistically lower mean endothelial cell density (2,193.40 ± 313.37 versus 2,385.08 ± 357.80 cells/ mm2; P = .019), and a statistically higher prevalence of corneal guttata (25.0% versus 8.8%; P = .015). None of the other analyzed variables statistically differed between the groups (P > .05). The risk of having Descemet membrane detachment was statistically higher among eyes with guttata (odds ratio = 3.47; P = .015) and in those with an endothelial cell density of less than 2,000 cells/mm2 (odds ratio = 3.26; P = .014). CONCLUSIONS: The incidence of Descemet membrane detachment due to laser application in FLACS was 3.9%, with the associated risk factors being endothelial cell density of less than 2,000 cells/mm2 and corneal guttata. [J Refract Surg. 2021;37(7):466-471.].

Subfoveal perfluorocarbon liquid removal by peeling of internal limiting membrane, without retinotomy.

Perfluorocarbon liquid has been widely used during vitreoretinal operations. Subretinal retention is a rare intraoperative complication, but even small quantities can damage the macular structure and function, and no standard treatment has been established. We encountered a 43-year-old woman who presented a retained subfoveal bubble after a vitreoretinal operation due to primary rhegmatogenous retinal detachment. Herein, we describe the procedure we used to remove the perfluorocarbon liquid without retinotomy using internal limiting membrane peeling.

Subfoveal perfluorocarbon liquid removal by peeling of internal limiting membrane, without retinotomy / Remoção de perfluorocarbono líquido subfoveal, sem retinotomia, através do peeling da membrana limitante interna

ABSTRACT Perfluorocarbon liquid has been widely used during vitreoretinal operations. Subretinal retention is a rare intraoperative complication, but even small quantities can damage the macular structure and function, and no standard treatment has been established. We encountered a 43-year-old woman who presented a retained subfoveal bubble after a vitreoretinal operation due to primary rhegmatogenous retinal detachment. Herein, we describe the procedure we used to remove the perfluorocarbon liquid without retinotomy using internal limiting membrane peeling.

RESUMO O perfluorocarbono líquido tem sido amplamente durante cirurgias vitreorretinianas. A retenção subretiniana, é uma complicação intraoperatória rara, mas mesmo pequenas quantidades podem danificar a estrutura e função macular, e nenhum tratamento padrão foi estabelecido. Encontramos uma mulher de 43 anos que apresentou bolha subfoveal retida após uma cirurgia vitreorretiniana devido a descolamento de retina regmatogênico. Aqui, descrevemos o procedimento que usamos para remover o líquido perfluorocarbono sem retinotomia usando peeling da membrana limitante interna.

Efficacy of preoperative nonsteroidal anti-inflammatory drug and the re-dilation technique in minimizing miosis after femtosecond laser in cataract surgery / Eficácia do AINE pré-operatório e da técnica de re-dilatação em minimizar a miose na cirurgia de catarata com laser de femtosegundo

ABSTRACT Purpose: To assess the efficacy of using a nonste­roidal anti-inflammatory drug preoperatively and of applying the re-dilation technique when necessary to minimize pupil size variation when comparing the degree of mydriasis before femtosecond laser pretreatment with that at the beginning of phacoemulsification. Methods: This retrospective study included patients who underwent cataract surgery using the LenSx (Alcon Laboratories, Inc., Fort Worth, TX). Our routine dilating regimen with flurbiprofen, tropicamide, and phenylephrine was used. The re-dilation technique was applied on eyes that manifested with a pupillary diameter that was smaller than the programmed capsulotomy diameter after laser pretreatment. The technique consists of overcoming pupillary contraction by instilling tropicamide and phenylephrine before phacoemulsification. Pupil size was assessed before femtosecond laser application and at the beginning of phacoemulsification. Results: Seventy-five eyes (70 patients) were included. Nine (12%) eyes underwent the re-dilation technique. There was no significant difference in mean pupillary diameter and mean pupillary area between the two studied surgical time points (p=0.412 and 0.437, respectively). The overall pupillary area constriction was 2.4 mm2. Immediately before opening the wounds for phacoemulsification, none of the eyes presented with a pupillary diameter <5 mm, and 61 (85.3%) eyes had a pupillary diameter >6 mm. Conclusion: Preoperative administration of nonsteroidal anti-inflammatory drug and the re-dilation technique resulted in no significant pupil size variation in eyes that were pretreated with the femtosecond laser, when comparing the measurements made before the laser application and at the beginning of phacoemulsification. This approach can avoid the need to proceed with cataract extraction with a constricted pupil.

RESUMO Objetivo: Avaliar a eficácia do uso de anti-inflamatório não-esteróide no pré-operatório e aplicação da técnica de re-dilatação quando necessária para minimizar a variação do tamanho pupilar ao comparar o grau de midríase antes do tra­tamento com laser de femtosegundo no início da facoemulsificação. Métodos: Esse estudo retrospectivo incluiu pacientes que foram submetidos à cirurgia de catarata usando o LenSx (Alcon Laboratories, Inc., Fort Worth, TX). Nosso regime de di­latação de rotina com flurbiprofeno, tropicamida e fenilefrina foi usado. A técnica de re-dilatação doi aplicada em olhos que se manifestaram com um diâmetro pupilar menor do que o diâmetro da capsulotomia programado após o pré-tratamento a laser. A técnica consiste em superar a contração pupilar pela instilação de tropicamida e fenilefrina antes da facoemulsificação. O tamanho pupilar foi avaliado antes da aplicação do laser de femtosegundo e no inicio da facoemulsificação. Resultados: Setenta e cinco olhos (70 pacientes) foram incluídos. Nove (12%) olhos foram submetidos à técnica de re-dilatação. Não houve diferença significativa no diâmetro pupilar médio e na área pupilar média entre os dois tempos cirúrgicos estudados (p=0,412 e 0,437, respectivamente). A constrição global da área pupilar foi de 2,4 mm2. Imediatamente antes de abrir as incisões para a facoemulsificação, nenhum dos olhos apresentava diâmetro pupilar <5 mm e 61 (85,3%) olhos apresentavam um diâmetro pupilar >6 mm. Conclusões: O administração pré-operatória de anti-inflamatório não-esteróide e da técnica de re-dilatação resultaram em uma variação significativa do tamanho pupilar em olhos que foram pré-tratados com laser de femtosegundo, comparando as medidas realizadas antes da aplicação do laser e no inicio da facoemulsificação. Essa abordagem pode evitar a necessidade de prosseguir com a extração da catarata com uma pupila contraída.

Efficacy of preoperative nonsteroidal anti-inflammatory drug and the re-dilation technique in minimizing miosis after femtosecond laser in cataract surgery.

PURPOSE: To assess the efficacy of using a nonste-roidal anti-inflammatory drug preoperatively and of applying the re-dilation technique when necessary to minimize pupil size variation when comparing the degree of mydriasis before femtosecond laser pretreatment with that at the beginning of phacoemulsification. METHODS: This retrospective study included patients who underwent cataract surgery using the LenSx (Alcon Laboratories, Inc., Fort Worth, TX). Our routine dilating regimen with flurbiprofen, tropicamide, and phenylephrine was used. The re-dilation technique was applied on eyes that manifested with a pupillary diameter that was smaller than the programmed capsulotomy diameter after laser pretreatment. The technique consists of overcoming pupillary contraction by instilling tropicamide and phenylephrine before phacoemulsification. Pupil size was assessed before femtosecond laser application and at the beginning of phacoemulsification. RESULTS: Seventy-five eyes (70 patients) were included. Nine (12%) eyes underwent the re-dilation technique. There was no significant difference in mean pupillary diameter and mean pupillary area between the two studied surgical time points (p=0.412 and 0.437, respectively). The overall pupillary area constriction was 2.4 mm2. Immediately before opening the wounds for phacoemulsification, none of the eyes presented with a pupillary diameter <5 mm, and 61 (85.3%) eyes had a pupillary diameter >6 mm. CONCLUSION: Preoperative administration of nonsteroidal anti-inflammatory drug and the re-dilation technique resulted in no significant pupil size variation in eyes that were pretreated with the femtosecond laser, when comparing the measurements made before the laser application and at the beginning of phacoemulsification. This approach can avoid the need to proceed with cataract extraction with a constricted pupil.

Ebselen Attenuates Lung Injury in Experimental Model of Carrageenan-Induced Pleurisy in Rats.

The study evaluates the role of Ebselen (Eb), an organoselenium compound in animal model of acute lung injury induced by carrageenan (CG). Wistar rats received saline or 2 % λ-carrageenan in the pleural cavity, and treatment with Eb (50 mg/kg intragastrically) or dexamethasone (Dx) (0.5 mg/kg intraperitoneal) after CG administration. After 4 h, rats were euthanized and the pleural exudate removed for analysis of the total cell count, total protein, lactate dehydrogenase, and nitrite/nitrate. Moreover, lung tissue were removed to verify the myeloperoxidase activity and oxidative damage. Eb showed anti-inflammatory activity by inhibiting leukocyte influx, myeloperoxidase activity, and nitrite/nitrate concentration. Eb presented with an anti-inflammatory activity similar to Dx and an antioxidant activity better than Dx. This study suggests that Eb plays an important role against the oxidative damage associated with anti-inflammatory activity in animal model of acute lung injury, proving to be similar or potentially more effective than Dx.

Effects of organoselenium compounds on early and late brain biochemical alterations in sepsis-survivor rats.

Studies have consistently reported the participation of oxidative stress, energetic metabolism impairment, and creatine kinase (CK) activity alterations in rat brain in early times in an animal model of sepsis and persist for up to 10 days. We have assessed the antioxidant effects of administration of Ebselen (Eb) e diphenyl diselenide (PhSe)2 two organoselenium compounds on brain oxidative stress, energetic metabolism, and CK activity 12, 24 h, and 10 days after sepsis by cecal ligation and perforation (CLP) in rats. Male Wistar rats underwent either sham operation or CLP and were treated with oral injection of Eb (50 mg/kg) or (PhSe)2 (50 mg/kg) or vehicle. 12, 24 h, and 10 days after CLP, the rats were sacrificed, and samples from brain (hippocampus, striatum, cerebellum, prefrontal cortex, and cortex) were obtained and assayed for thiobarbituric acid reactive species and protein carbonyls formation, mitochondrial respiratory chain, and CK activity. We observed in the results a reduction of oxidative damage to lipids and proteins in the different cerebral structures studied and times with the administration of (PhSe)2; however, Eb seems to exert the same effect. Such changes are reflected in the assessment of mitochondrial respiratory chain complexes by reversing the decreased activity of the complex caused by the model of CLP and CK activity. Our data provide the first experimental demonstration that (PhSe)2 was able to reduce the brain dysfunction associated with CLP-induced sepsis in rats, by decreasing oxidative stress parameters mitochondrial dysfunction and CK activity in early times and in late time.