Self-Assembling Topical Nanomicellar Formulation to Improve Curcumin Absorption Across Ocular Tissues

Alshamrani, Meshal; Sikder, Sadia; Coulibaly, Fohona S.; Mandal, Abhirup; Pal, Dhananjay

doi:10.1208/s12249-019-1404-1

Cited by 30 publications

(15 citation statements)

References 31 publications

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“…This suggests indicated that dilution up to 200 times had very little effect on the nanomicellar size and significant change in PDI and zeta potential. Similar results were obtained in a previously reported study, where similar polymers were used to enhance ocular drug delivery of triamcinolone acetonide and curcumin [30,44]. Lyophilized TAC-NMF was also dissolved in CDCL 3 so that the drug in the core of the nanomicelles could be released in the solution for quantification.…”

Section: Nanomicellar Dilution Studysupporting

confidence: 82%

“…For topically instilled formulations, viscosity plays an important role in the mean residence time of the formulation and its drainage. Similarly, ophthalmic formulations administered intravitreally should have a viscosity between that of water and vitreal humor fluid [44]. The viscosity of the optimized F-6 formulation was 1.12 ± 0.05 cP (mean ± SD) (n = 3), at RT.…”

Section: Critical Micellar Concentration and Nanomicellar Viscosity Amentioning

confidence: 99%

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Self-Assembling Tacrolimus Nanomicelles for Retinal Drug Delivery

et al. 2020

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Neovascular age-related macular degeneration (AMD) is characterized by an increase in reactive oxygen species (ROS) and pro-inflammatory cytokines in the retinal pigment epithelium cells. The primary purpose of this study was the development of a clear, tacrolimus nanomicellar formulation (TAC-NMF) for AMD. The optimized formulation had a mean diameter of 15.41 nm, a zeta potential of 0.5 mV, and an entrapment efficiency of 97.13%. In-vitro cytotoxicity studies revealed the dose-dependent cytotoxicity of TAC-NMF on various ocular cell lines, such as human retinal pigment epithelium (D407), monkey retinal choroidal endothelial (RF/6A) cells, and human corneal epithelium (CCL 20.2) cells. Cellular uptake and in-vitro distribution studies using flow cytometry and confocal microscopy, respectively, indicated an elevated uptake of TAC-NMF in a time-dependent manner. Biocompatibility assay using macrophage RAW 264.7 cell line resulted in low production of inflammatory cytokines such as IL-6, IL-1β and TNF-α after treatment with TAC-NMF. There was a decrease in ROS in D407 cells pre-treated with sodium iodate (ROS inducing agent) after treating with TAC-NMF and tacrolimus drug. Similarly, there was a reduction in the pro-inflammatory cytokines and VEGF-A in D407 cells pretreated with sodium iodate. This indicates that TAC-NMF could lower pro-inflammatory cytokines and ROS commonly seen in AMD.

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Section: Nanomicellar Dilution Studysupporting

confidence: 82%

Section: Critical Micellar Concentration and Nanomicellar Viscosity Amentioning

confidence: 99%

Self-Assembling Tacrolimus Nanomicelles for Retinal Drug Delivery

et al. 2020

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“…This result confirmed that the excellent anti-UM effect showed in Figure 9 was attributed to sustained Cur release from the Cur NP/Gel composite. Despite that the hydrogel components (i.e., collagen and hyaluronic acid) have excellent biocompatibility and good ocular safety of curcumin has been previously demonstrated using cell lines such as human retinal pigmented epithelial (D407) cells [70], 661W and ARPE-19 retinal cells [71], the ocular safety of the developed Cur NP/Gel composite needs to be investigated using an animal model in the future. ponents (i.e., collagen and hyaluronic acid) have excellent biocompatibility and good ocular safety of curcumin has been previously demonstrated using cell lines such as human retinal pigmented epithelial (D407) cells [70], 661W and ARPE-19 retinal cells [71], the ocular safety of the developed Cur NP/Gel composite needs to be investigated using an animal model in the future.…”

Section: In Vitro Anti-um Effect Of Cur Co-ha Gel Compositesmentioning

confidence: 99%

A Long-Acting Curcumin Nanoparticle/In Situ Hydrogel Composite for the Treatment of Uveal Melanoma

et al. 2021

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Uveal melanoma (UM) is the most common primary intraocular tumor in adults with high mortality. In order to improve prognosis and survival of UM patients, it is critical to inhibit tumor progression and metastasis as early as possible after the initial presentation/diagnosis of the disease. Sustained local delivery of antitumor therapeutics in the posterior region can potentially achieve long-term UM inhibition, improve target therapeutic delivery to the posterior segments, as well as reduce injection frequency and hence improved patient compliance. To address the highly unmet medical need in UM therapy, a bioinspired in situ gelling hydrogel system composed of naturally occurring biopolymers collagen and hyaluronic acid was developed in the present research. Curcumin with anti-cancer progression, anti-metastasis effects, and good ocular safety was chosen as the model therapeutic. The developed in situ gelling delivery system gelled at 37 °C within two minutes and demonstrated excellent biocompatibility and slow degradation. The curcumin-loaded nanoparticle/hydrogel composite was able to sustain release payload for up to four weeks. The optimized nanoparticle/hydrogel composite showed effective inhibition of human UM cell proliferation. This novel nanoparticle/in situ hydrogel composite demonstrated a great potential for the treatment of the rare and devastating intraocular cancer.

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“…Conversely, Alshamrani et al developed an aqueous nanomicellar drop formulation of curcumin (CUR-NMF) utilizing hydrogenated castor oil (HCO-40) and octoxynol-40 (OC-40) in order to treat AMD. 107 …”

Section: Curcumin Delivery Systems ( Table 1 )mentioning

confidence: 99%

Recent Advances and Disputes About Curcumin in Retinal Diseases

Nebbioso¹,

Franzone²,

Greco³

et al. 2021

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Curcumin belongs to the group of so-called phytocompounds, biologically active molecules produced by plants exerting a beneficial effect on health. Curcumin shows a wide spectrum of different properties, being an anti-inflammatory, antioxidant, antimicrobial and antimutagenic molecule. The purpose of the review is to examine what literature reported on the characteristics of curcumin, particularly, on the beneficial and controversial aspects of this molecule, aiming for a better therapeutic management of retinal diseases. The retina is a constant target of oxidative stress, this tissue being characterized by cells rich in mitochondria and by vessels and being, obviously, continuously reached from photons affecting its layers. Particularly, the retinal ganglion cells and the photoreceptors are extremely sensitive to oxidative stress damage and it is well known that an imbalance in reactive oxygen species is often involved in several retinal diseases, such as uveitis, age-related macular degeneration, diabetic retinopathy, central serous chorioretinopathy, macular edema, retinal ischemia-reperfusion injury, proliferative vitreoretinopathy, hereditary tapeto-retinal degenerations, and retinal and choroidal tumors. To date, several studies suggest that oral treatment with curcumin is generally well tolerated in humans and, in addition, it seems to have no negative effects: therefore, curcumin is a promising candidate as a retinal disease therapy. Unfortunately, the primary limitation of curcumin is represented by its poor bioavailability, in fact only a minimal fraction of this substance can reach the blood stream in the form of a biologically active compound. However, many steps have been made in several fields. In the future, it is expected that the strategies developed until now to allow curcumin to reach the target tissues in adequate concentrations could be ameliorated and, above all, large in vivo studies on humans are needed to demonstrate the total safety of these compounds and their effectiveness in different eye diseases.

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Self-Assembling Topical Nanomicellar Formulation to Improve Curcumin Absorption Across Ocular Tissues

Cited by 30 publications

References 31 publications

Self-Assembling Tacrolimus Nanomicelles for Retinal Drug Delivery

Self-Assembling Tacrolimus Nanomicelles for Retinal Drug Delivery

A Long-Acting Curcumin Nanoparticle/In Situ Hydrogel Composite for the Treatment of Uveal Melanoma

Recent Advances and Disputes About Curcumin in Retinal Diseases

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