Self-Assembling Tacrolimus Nanomicelles for Retinal Drug Delivery

Abstract

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.

Hyaluronic Acid-Targeted Stimuli-Sensitive Nanomicelles Co-Encapsulating Paclitaxel and Ritonavir to Overcome Multi-Drug Resistance in Metastatic Breast Cancer and Triple-Negative Breast Cancer Cells

“…Such nanomicelles can be utilized to entrap hydrophobic drugs in their core. Thus, they can serve as excellent drug delivery vehicles for hydrophobic drugs and support in improving their solubility [ 9 , 10 , 11 ]. Here, we prepared HA − PTX + RTV − NMF using a mixture of polymers like HA−ss−PLGA and Vit E-TPGS.…”

“…In summary, the combination therapy of anticancer drugs with RTV can overcome drug resistance by deactivating the overexpression of efflux transporters and metabolizing enzymes. In another study, we demonstrated the inhibition of the hypoxia-induced overexpression of HIF-α and, consequently, overproduction of VEGF and endothelial proliferation by [ 10 ]. Therefore, we anticipate that anti-cancer drug regimens containing RTV would enhance the therapeutic exposure of cancer cells to anticancer agents, potentially improving chemotherapeutic efficacy, devoid of drug resistance.…”

Diabetic eye: associated diseases, drugs in clinic, and role of self-assembled carriers in topical treatment

“…micelles made of PEG-hydrogenated castor oil-40 and octyxonyl-40, which have low CMC and provide slow drug release. Tacrolimus-loaded micelles showed faster cell internalization than the free drug [129]. Mixed micelles of polyoxyl 40 stearate and polysorbate 80 successfully delivered dexamethasone (0.1%) to the back of the eye, providing therapeutic drug levels in retina and choroid after eye drop instillation [130].…”

Amphiphilic Carboxymethyl Dextran Nanomicelles for Antibacterial Coating on Titanium

“…In recent years, nanomicelles, due to their small particle size, excellent stability, high drug loading, sustained release, have been applied in various biological and medical fields, such as Cancer-targeted therapy [16][17][18][19] , and ophthalmologic disease [20]. Nanomicelles are nano-sized colloidal carriers characterized by core-shell structures consisting of the exterior hydrophilic polar head and interior hydrophobic tail.…”