Lipid Nanoparticles as Carriers for the Treatment of Neurodegeneration Associated with Alzheimer’s Disease and Glaucoma: Present and Future Challenges

López, Elena Sánchez; Machado, Ana López; Vidal, Lorena B; González-Pizarro, Roberto; Silva, Amélia M.; Souto, Eliana B.

doi:10.2174/1381612826666200218101231

Cited by 16 publications

(12 citation statements)

References 83 publications

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“…Cerium oxide nanoparticles, known for their antioxidant properties, have been proposed for the treatment of cataracts [70],-an eye condition associated with changes in the structural proteins of the lens and intimately related to other age-related neurodegenerative diseases such as Alzheimer's [74]. The risk of DNA damage has been evaluated on cultured human lens epithelial cells using the alkaline comet assay.…”

Section: Lens (Human)mentioning

confidence: 99%

Ocular Cell Lines and Genotoxicity Assessment

Souto

Campos

Ana

et al. 2020

IJERPH

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Genotoxicity screening tests aim to evaluate if and to what extent a compound in contact with the human body (e.g., a drug molecule, a compound from the environment) interacts with DNA. The comet assay is a sensitive method used to predict the risk of DNA damage in individual cells, as it quantifies the tape breaks, being the alkaline version (pH > 13) the most commonly used in the laboratory. Epithelial cells serve as biomatrices in genotoxicity assessments. As ca. 80% of solid cancers are of epithelial origin, the quantification of the DNA damage upon exposure of epithelial cells to a drug or drug formulation becomes relevant. Comet assays run in epithelial cells also have clinical applications in human biomonitoring, which assesses whether and to what extent is the human body exposed to environmental genotoxic compounds and how such exposure changes over time. Ocular mucosa is particularly exposed to environmental assaults. This review summarizes the published data on the genotoxicity assessment in estimating DNA damage in epithelial cells with a special focus on ocular cell lines. General comet assay procedures for ex vivo and in vivo epithelium samples are also described.

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Section: Lens (Human)mentioning

confidence: 99%

Ocular Cell Lines and Genotoxicity Assessment

Souto

Campos

Ana

et al. 2020

IJERPH

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“…Deleterious free-radical reactions have been linked to a variety of degenerative pathological conditions including cancer, autoimmune disorders, cataract, rheumatoid arthritis, cardiovascular and neurodegenerative diseases [50][51][52][53]. This effect has been described as a consequence of the Figure 3 shows photomicrographs obtained by SEM at two distinct processing conditions; showing the presence of irregular to rounded powder particles, with polydisperse characteristics.…”

Section: Antioxidant Activity Of the Concentrated And Dried Rosemary Extractsmentioning

confidence: 99%

Section: Antioxidant Activity Of the Concentrated And Dried Rosemary Extractsmentioning

confidence: 99%

“…Deleterious free-radical reactions have been linked to a variety of degenerative pathological conditions including cancer, autoimmune disorders, cataract, rheumatoid arthritis, cardiovascular and neurodegenerative diseases [50][51][52][53]. This effect has been described as a consequence of the involvement of reactive oxygen species in initiating autoxidation of cellular lipid membranes, which are mainly composed of polyunsaturated fatty acids, leading to cellular necrosis [54,55].…”

Section: Antioxidant Activity Of the Concentrated And Dried Rosemary Extractsmentioning

confidence: 99%

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Spouted Bed Dried Rosmarinus officinalis Extract: A Novel Approach for Physicochemical Properties and Antioxidant Activity

et al. 2020

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In this study, a conical-cylindrical spouted bed dryer with Teflon® beads as spouting material was used for producing powdered rosemary (Rosmarinus officinalis L.) extract. The influence of the inlet drying gas temperature (Tgi) and the percentage ratio between the feed rate of concentrated liquid extract by the maximum evaporation capacity of the spouted bed (Ws/Wmax) on selected physicochemical properties of the finished products were investigated. Antioxidant properties of the concentrated liquid extract and dried extracts were also evaluated by the 2.2-diphenyl-1-picrylhydrazyl radical scavenging (DPPH) and lipid peroxidation induced by Fe2+/citrate (LPO) methods; and compared with the values obtained for a lyophilized extract (used as a control). Colloidal silicon dioxide (Tixosil® 333) and maltodextrin (DE 14) at a 2:1 ratio was added to the concentrated extract before drying (4.4% w/w) to improve the drying performance. The drying variables Ws/Wmax and Tgi have statistically significant influence on total polyphenols and total flavonoid contents of the dried powders. The concentrated extract (on dry basis—being absolute solid content) showed superior antioxidant activity (AA) compared to both the spouted bed dried and the lyophilized extracts; exhibiting IC50 values of 0.96 ± 0.02, 2.16 ± 0.04 and 3.79 ± 0.05 µg mL−1 (DPPH method) and 0.22 ± 0.01, 1.31± 0.01 and 2.54 ± 0.02 µg mL−1 (LPO method), respectively. These results of AA are comparable to values obtained for quercetin, a flavonoid compound often used as a reference standard due to its potent antioxidant activity; with IC50 of 1.17 µg mL−1 (DPPH) and 0.22 µg mL−1 (LPO). However, the dried rosemary extracts are about 13.5 times more concentrated than the initial concentrated extract (dry weight), with a concentration of total flavonoids and polyphenols compounds ranging from 4.3 to 12.3 and from 1.2 to 4.7 times higher than the concentrated extract values (wet basis). The AA per dry product mass was thus significantly higher than the values measured for concentrated extractive solution, irrespective of some losses of AA apparently due to the drying process.

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“…Phosphatidylserine (PS), a cell membrane phospholipid, plays an important role in apoptosis and cell cycle signaling 12–14 . The arrangement of lipid–polymer NPs has also been a subject for reasearch due to their special properties, which can alleviate some drawbacks allied with polymeric NPs and liposomes 15–17 .…”

Section: Introductionmentioning

confidence: 99%

Brinzolamide loaded core-shell nanoparticles for enhanced coronial penetration in the treatment of glaucoma

Song

Zhang

2020

Journal of Applied Biomaterials & Functional Materials

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A neurodegenerative disorder, glaucoma is a leading cause of blindness in the world. The conventional treatment strategies do not allow the significant penetration of the drug in the cornea. Therefore, we prepare a brinzolamide (Brz) loaded core-shell nanoparticles (NPs) to enhance the coronial penetration of the drug and thus treating the glaucoma. The shell of the NPs was composed of phosphatidylserine (PS; 1,2-diacyl-sn-glycero-3-phospho-L-serine), whereas the core of the NPs contains the Brz encapsulated in brinzolamide–phosphatidylserine–polymer poly-(DL-lactic acid-co-glycolic acid)–phosphatidylserine (Brz-PS-PLGA). The synthesis of Brz-PS-PLGA was achieved by using a coaxial electrospray process (CEP), which allows the preparation of the particles in a single step. The size of Brz-PS-PLGA with PS shell and brinzolamide–poly (lactic-co-glycolic) acid (Brz-PLGA) without shell was 571 ± 27.02 nm and 456 ± 19.17 nm, respectively. The charges on the surface of Brz-PS-PLGA and Brz-PLGA were (-) 27.45 ± 2.98 mV and (-) 19.47 ± 2.83 mV. The transmission electron microscopy images clearly reveal the PS shell as a light black layer over the dark black PLGA core. The CEP allows the high encapsulation of Brz in Brz-PS-PLGA where percentage of entrapment efficiency for Brz-PS-PLGA was 88.13 ± 6.43%. The release study conducted in a simulated tear fluid revealed the sustained release patterns of Brz from Brz-PS-PLGA and these were nontoxic to the cells as revealed by the cytotoxicity studies. Further, the Brz-PS-PLGA enhanced the coronial penetration of Brz and was capable of significantly reducing the intraocular pressure (IOP) after administration to the rabbit eye in comparison to the Brz-PLGA and free Brz. The results clearly suggest that the PS coating significantly enhances the capability of the particles in reducing IOP.

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Lipid Nanoparticles as Carriers for the Treatment of Neurodegeneration Associated with Alzheimer’s Disease and Glaucoma: Present and Future Challenges

Cited by 16 publications

References 83 publications

Ocular Cell Lines and Genotoxicity Assessment

Ocular Cell Lines and Genotoxicity Assessment

Spouted Bed Dried Rosmarinus officinalis Extract: A Novel Approach for Physicochemical Properties and Antioxidant Activity

Brinzolamide loaded core-shell nanoparticles for enhanced coronial penetration in the treatment of glaucoma

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