Development of Thiabendazole-Loaded Mesoporous Silica Nanoparticles for Cancer Therapy.

Thiabendazole (TBZ) is an anthelmintic drug currently studied for anticancer purposes. However, due to its low solubility, its biomedical application has been limited. Using mesoporous silica nanoparticles (MSNPs), such as Mobil Composition of Matter Number 41 (MCM-41), as a drug carrier, is a promising approach to improve the solubility of low water-soluble drugs. In the present work, we aim to develop TBZ-loaded MCM-41 (TBZ MCM-41) nanoparticles to improve the solubility and the therapeutic efficacy of TBZ against prostate cancer PC-3 cells. TBZ MCM-41 nanoparticles were synthesized with a size of 215.9 ± 0.07 nm, a spherical shape, a hexagonal array of channels, and a drug loading capacity of 19.1%. The biological effects of the nanoformulation on PC-3 cells were then evaluated using a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT), IncuCyte live-cell imaging system, cell migration, and reactive oxygen species (ROS) assays. The results demonstrated that TBZ was released from MCM-41 nanoparticles in a controlled manner at pH values of 1.2 and 6.8. The cell viability measurements revealed that the TBZ MCM-41 nanoparticles caused a considerable 2.8-fold increase in the cytotoxicity of TBZ (IC50 127.3 and 46 µM for TBZ and TBZ MCM-41 nanoparticles, respectively). The results of the proliferation assay were in agreement with those of the cell viability measurements, where the MCM-41 increased the cytotoxicity of TBZ in a concentration-dependent manner. Also, the TBZ MCM-41 nanoparticles were found to enhance the potency of the drug and inhibit PC-3 cell migration. In addition, the ROS assay confirmed that TBZ MCM-41 nanoparticles were approximately 15% more potent than TBZ to produce ROS. Overall, the results demonstrated that MCM-41 nanoparticles are a promising carrier to improve the therapeutic efficacy of TBZ against PC-3 cells and suggest evaluating the efficacy of the formulation in vivo.

PEGylated Mesoporous Silica Nanoparticles (MCM-41): A Promising Carrier for the Targeted Delivery of Fenbendazole into Prostrate Cancer Cells.

Low water solubility and thus low bioavailability limit the clinical application of fenbendazole (FBZ) as a potential anticancer drug. Solubilizing agents, such as Mobil Composition of Matter Number 41 (MCM) as a drug carrier, can improve the water solubility of drugs. In this study, PEGylated MCM (PEG-MCM) nanoparticles (NPs) were synthesized and loaded with FBZ (PEG-MCM-FBZ) to improve its solubility and, as a result, its cytotoxicity effect against human prostate cancer PC-3 cells. The loading efficiency of FBZ onto PEG-MCM NPs was 17.2%. The size and zeta potential of PEG-MCM-FBZ NPs were 366.3 ± 6.9 nm and 24.7 ± 0.4 mV, respectively. They had a spherical shape and released the drug in a controlled manner at pH 1.2 and pH 6.2. PEG-MCM-FBZ were found to inhibit the migration of PC-3 cells, increase the cytotoxicity effects of FBZ against PC-3 cells by 3.8-fold, and were more potent by 1.4-fold, when compared to the non-PEGylated NPs. In addition, PEG-MCM-FBZ promoted the production of reactive oxygen species by 1.3- and 1.2-fold, respectively, when compared to FBZ and MCM-FBZ. Overall, the results demonstrate that PEG-MCM-FBZ NPs enhanced FBZ delivery to PC-3 cells; therefore, they have the potential to treat prostate cancer after a comprehensive in vivo study.

Effect of gold nanoparticles on properties of nanoliposomal hydroxyurea: an in vitro study.

New hopes in cancer treatment have been emerged using functional nanoparticles. In this work, we tried to synthesize gold nanoparticles and gold nanoparticles conjugated with DNA extracted from human breast cancer cells. After synthesizing, gold nanoparticles were mixed with nanoliposomal hydroxyurea and corresponding compounds were formed. They were described by UV-Visible spectrophotometry and Zeta sizer. Amount of drug loading into liposomes was determined by spectrophotometry and cytotoxicity effect on MCF-7 cells was measure by MTT assay. Drug loading was determined to be 70 %. Size, size distribution and Zeta potential of particles were 473 nm, 0.46 and -21 mV for control nanoliposomal ones and 351 nm, 0.38 and -25 mV for nanoliposomal particles containing hydroxyurea. This was 29 nm, 0.23 and -30 mV for gold nanoparticles and 502 nm, 0.41 and -38 mV for nanoliposomes containing drug loaded by gold nanoparticles conjugated with DNA. It was found that nano conjugated complex in concentrations less than 20 µM of hydroxyurea can improve efficiency compared with liposomal drug. In maximum concentration of drug (2,500 µM), cytotoxicity was equal to 95 %. In minimum concentration of drug (5 µM), cytotoxicity of liposomal drug and conjugated complex were 70 and 81 %, respectively which probably comes from increased drug entry into cells due to the presence of gold nanoparticles. Free drug resulted in toxicity of 32 % in 5 µM and 88 % in 2,500 µM. Results demonstrated higher drug efficiency in nanoparticle form compared with free form which can be used in in vivo studies.

Archaeosome: as new drug carrier for delivery of Paclitaxel to breast cancer.

In the present study, paclitaxel was archaeosomed to reduce side effects and improve its therapeutic index. Carriers have made a big evolution in treatment of many diseases in recent years. Lipid carriers are of special importance among carriers. Archaeosome is one of the lipid carriers. Paclitaxel is one of the drugs used to treat breast cancer which has some unwanted side effects despite its therapeutic effects. Archaeosomes were extracted from methanogenic archi bacteria and synthesized with a certain ratio of paclitaxel in PBS. The mean diameter of archaeosomal paclitaxel was measured by Zeta sizer instrument, Drug releasing of archaeosomal paclitaxel was examined within 26 h which results showed that the most drug releasing occurs during first 3 h. The cytotoxicity effect of archaeosomal paclitaxel on breast cancer's cell line was evaluated by MTT assay which results showed that the cytotoxicity effect of archaeosomal paclitaxel on breast cancer's cell line is more than that of the standard paclitaxel formulation. The results indicated that new drug delivery of paclitaxel using archaeosome, increases the therapeutic index of the drug.

In vitro evaluation of the efficacy of liposomal and pegylated liposomal hydroxyurea.

Breast cancer is one of the most frequent cancer types within women population. Hydroxyurea (HU) is a chemotherapy compound for treatment of patients with cancer diagnosis, including breast cancer associated with several adverse effects. In this study, we applied nanotechnology to decreased drug side effects along with improvement of therapeutic index. Liposomation is widely used in modern pharmacological developments in order to enhance the effects of the drugs. To achieve this, in this study a mixture of phosphatidylcholine and cholesterol was made up and HU was added to the resultant mixture, was then pegylated using Polyethylene Glycol 2000 to increase resistance, applicability and solubility. The mean diameters of nanoliposomal and pegylated nanoliposomal HU were measured by Zeta sizer device and obtained about 402.5 and 338.2 nm. The efficiency of non-pegylated and pegylated liposomal HU was 70.8 and 64.2, respectively. Releasing HU in both formulations was estimated about 25.8 and 21.7 %. Also, this study investigated the cytotoxicity effect of nanoliposomal and pegylated nanoliposomal HU using MTT assay. Results of this investigation showed that the cytotoxic properties of pegylated HU was 3.6 % more than those non-pegylated form, while was 38.93 % more than ordinary from of HU. This study showed that the stability, releasing pattern and cytotoxicity of the pegylated nanoliposomal HU is better than that of nanoliposomal HU.

Modeling and prediction of cytotoxicity of artemisinin for treatment of the breast cancer by using artificial neural networks.

While artemisinin is known as anticancer medication with favorable remedial effects, its side effects must not be neglected. In order to reduce such side effects and increase artemisinin therapeutic index, nano technology has been considered as a new approach. Liposome preparation is supposed to be one of the new methods of drug delivery. To prepare the desired nanoliposome, certain proportions of phosphatidylcholine, cholesterol and artemisinin are mixed together. Besides, in order to achieve more stability, the formulation was pegylated by polyethylene glycol 2000 (PEG 2000). Mean diameter of nanoliposomes was determined by means of Zeta sizer. Encapsulation was calculated 96.02% in nanoliposomal and 91.62% in pegylated formulation. Compared to pegylated formulation, the percent of released drug in nanoliposomal formulation was more. In addition, this study reveals that cytotoxicity effect of pegylated nanoliposomal artemisinin was more than nanoliposomal artemisinin. Since artificial neural network shows high possibility of nonlinear modulation, it is used to predict cytotoxicity effect in this study, which can precisely indicate the cytotoxicity and IC50 of anticancer drugs.

Drug delivery of hydroxyurea to breast cancer using liposomes.

It is clear that cancer is one of the most mortal diseases in the world and the most prevalent among women is breast cancer. As hydroxyurea (HU)-a drug which is used in chemotherapy-has many adverse effects in long-term despite of its therapeutic properties, we made use of nano drug delivery technology in order to reduce adverse effects and increase therapeutic index. Thus, liposomation is a novel way in drug delivery systems. In this study a mixture of phosphatidylcholine and cholesterol was mixed and HU was added to the resultant mixture. The mean diameter of the nanoliposomal HU measured with the Zeta Sizer device (equal to 402.5 nm) and its encapsulation efficiency was 70.8 %. Besides, using dialysis, the pattern of drug release from nanoliposomes has been studied and the results showed that the drug release of nanoliposomal drug within 28 h was equal to 25.85 %. This study showed that the cytotoxicity effect of nanoliposomal drug is more than that of the standard drug.

Cytotoxicity of liposomal Paclitaxel in breast cancer cell line mcf-7.

Regarding that the breast cancer is the most prevalent disease among women, paclitaxel, an anti-cancer drug, could be used in treatment of this disease. As paclitaxel has adverse effects, it was used of nanoliposome drug delivery technology in order to reduce adverse effects and improve drug efficacy. Certain ratios of phosphatidylcholine, cholesterol and paclitaxel were synthesized to prepare nanoliposomal paclitaxel. Using Zeta sizer device, the mean diameter of nanoliposomal paclitaxel was obtained 421.4 nm and its encapsulation efficiency was 91.3 %. By dialysis, drug release in nanoliposome paclitaxel formulation within 28 h was studied which was 5.53 %. This study showed that cytotoxicity effect of nanoliposomal paclitaxel is more than that of the standard form.

Study of toxicity effect of pegylated nanoliposomal artemisinin on breast cancer cell line.

Nano carriers have greatly revolutionized the treatment of most diseases recently. One of these nano carriers, liposomes, has got particular significance. On the other hand, Artemisinin which is used as an effective anticancer drug has some side effects. To reduce such side effects, liposomes can be employed. In order to prepare pegylated nanoliposomal artemisinin, particular proportions of phosphatidylcholine, polyethylene glycol 2000 and artemisinin were combined. As a result, the mean diameter of nano liposomes is 455 nm. Besides, the encapsulation efficiency and the drug release from pegylated nanoliposomes for pegylated nanoliposomal artemisinin are respectively 91.62 ± 3.5 and 5.17 %. The results also show that IC50 of the produced formulation is less than that of the standard drug. This study reveals that the amount of artemisinin cytotoxicity compared to standard drug is increased by pegylated nanoliposomal formulation.