Evaluation of cyclosporine A eye penetration after administration of liposomal or conventional forms in animal model

Abstract A lot of researches have investigated the effects of topical cyclosporine A on the eye surface layers’ diseases. By now the main limitation in cyclosporine application is the low permeation of the drug into the posterior segments of the eye. The aim of present study was to formulate high permeable dosage form can be beneficial in the topical treatment of the uveitis. To reach higher corneal drug absorption and drug concentration in the posterior segments of the eye, 3 nanoliposomal formulations containing 0.5 mg/ml cyclosporine A were prepared. Liposomal formulations and the commercial product (Restasis®) were instilled in the right and left eyes of the rabbits, respectively. The rabbits were killed in the 3, 7, 14 and 28 days of study and the aqueous humor and vitreous were extracted. Mean size of liposomal formulation number 1, number 2 and number 3 were 107.2 ± 0.7, 129.3±0.9 and 144.8±1.8 nm and their zeta potential were -5.0±1.7, -5.5±2.3 and 44.6±6.2 mV, respectively. Results of ocular analysis showed that the liposomal formulations could increase the concentration of the drug in the aqueous and vitreous like Restasis®. But, in contrast with what has been expected the findings of this study implicate nanoliposomal formulations prepared could not make a significant difference in concentration of the drug in aqueous and vitreous humor compared to Restasis® (anionic microemulsion). In conclusion, we can state that liposomes with the same composition as our formulations are not more efficient than microemulsion for cyclosporine as ophthalmic drug delivery

Incorporation of curcumin into collagen-multiwalled carbon nanotubes nanocomposite scaffold: an in vitro and in vivo study

Aim: Fabrication of biological substitutes to regenerate damaged tissues or organs is one of the main aims of tissue engineering (TE). In this context, the goal of this study was to fabricate a scaffold that mimicked the structure and functions of the extracellular matrix (ECM) of the native tissues. Towards this aim, a novel biomimetic three-dimensional (3D) scaffold containing collagen (COL), multi-walled carbon nanotubes (MWCNTs), and curcumin (CUR) was created using the freeze-drying technique. Materials and methods: Scaffolds were prepared by adding 0.5–1.5% MWCNTs and 5–15% CUR to pure COL solutions, followed by freeze-drying. Physical and chemical characterizations of the scaffolds were evaluated by a universal testing machine, scanning electron microscope (SEM), fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). Biological studies were mainly focused on in-vitro bioactivity, biodegradability, CUR release, and in-vitro and in vivo biocompatibility using mesenchymal stem cells (MSCs) and rat animal models. Results: FTIR and XRD confirmed the presence of MWCNTs and CUR in the COL scaffolds, while SEM revealed highly interconnected porous morphology. Moreover, the addition of up to 1% MWCNTs and 10% CUR enhanced tensile strength from 5 MPa to 19 MPa. The developed COL-MWCNTs 1%-CUR 10% composite scaffolds revealed excellent surface wettability, in vitro bioactivity, and in vitro biocompatibility using rat synovial-derived MSCs (SM-MSCs). Importantly, the in vivo study revealed reduced inflammatory response in the rat animal model after six weeks of implantation, which could be attributed to the promising in vitro biodegradability and release of CUR. Conclusion: The newly developed COL-MWCNTs 1%-CUR 10% freeze-dried scaffolds have demonstrated their high potential for TE applications

The effect of RGD-targeted and non-targeted liposomal Galbanic acid on the therapeutic efficacy of pegylated liposomal doxorubicin

The anti-cancer therapeutic application of Galbanic acid (Gba) as a strong antiangiogenic sesquiterpene coumarin has been limited due to its low water solubility. This issue necessitates developing new liposomal formulations for the efficient delivery of Gba in vivo. In this study, various liposomal formulations were prepared by a thin-film hydration method, and Gba was incorporated into the liposomal bilayers, which consequently increased its release profile compared to formulations in our previous study prepared by remote loading methods. The most stable formulation with desired properties was selected and decorated with RGD peptide (cyclo [Arg-Gly-Asp-D-Tyr-Cys]) to target tumor vasculature actively. The fluorescently-labeled model liposomes showed that the targeting could improve the receptor-mediated endocytosis of the liposomes higher than those prepared in our previous study in vitro in human umbilical vein endothelial cells (HUVECs), which was confirmed by chicken chorioallantoic membrane angiogenesis (CAM) model in vivo. Although not significant, it also could increase the accumulation of liposomes in colon tumors. In BALB/c mice bearing colon cancer, not only non-targeted Gba liposomes but also even RGD-targeted ones combinatorial therapy with pegylated liposomal doxorubicin could improve the anti-tumor efficacy as compared to their monotherapy. These outcomes have strong consequences for cancer therapy.</p