Bile salt integrated cerasomes: A potential nanocarrier for enhancement of the oral bioavailability of idarubicin hydrochloride.

Cerasomes are a modified form of liposomes containing both inorganic and organic parts and due to their strong polyorganosiloxane surface have remarkably high morphological stability and provide easier functionalization compared with conventional liposomes. To investigate the potential of these nanocarriers for oral delivery, bile salt integrated cerasomes (named bilocerasomes) encapsulating idarubicin hydrochloride (IDA) were prepared and characterized. The optimum formulation showed excellent stability in the simulated gastrointestinal fluids as well as under storage conditions. The oral pharmacokinetics of the IDA solution, empty nanocarrier + drug solution, and IDA-loaded bilocerasome were evaluated. The nanoformulation significantly increased the area under the drug concentration-time curve and the mean residence time (∼14.3- and 9-fold, respectively). The results obtained from cell uptake and chylomicron flow blocking approach revealed that bilocerasomes are absorbed into the intestinal cells via a clathrin/caveolin-independent endocytosis pathway and transported to the systemic circulation extensively via the intestinal lymphatic vessels. Considering the high stability of the prepared bilocerasome, noticeable participation of lymphatic transport in its systemic absorption and marked enhancement in the oral absorption of IDA, bilocerasomes can be introduced as a capable carrier for improving the oral bioavailability of drugs, particularly those that hepatic first-pass metabolism seriously limits their oral absorption.

Bile salt-enriched vs. non-enriched nanoparticles: comparison of their physicochemical characteristics and release pattern.

Bile salts were first used in the preparation of nanoparticles due to their stabilizing effects. As time went by, they attracted much attention and were increasingly employed in fabricating nanoparticles. It is well accepted that the physicochemical properties of nanoparticles are influential factors in their permeation, distribution, elimination and degree of effectiveness as well as toxicity. The review of articles shows that the use of bile salts in the structure of nanocarriers may cause significant changes in their physicochemical properties. Hence, having information about the effect of bile salts on the properties of nanoparticles could be valuable in the design of optimal carriers. Herein, we review studies in which bile salts were used in preparing liposomes, niosomes and other nanocarriers. Furthermore, the effects of bile salts on entrapment efficiency, particle size, polydispersity index, zeta potential, release profile and stability of nanoparticles are pointed out. Finally, we debate how to take advantage of bile salts potential for preparing desirable nanocarriers.

Nanoparticles labeled with gamma-emitting radioisotopes: an attractive approach for in vivo tracking using SPECT imaging.

Providing accurate molecular imaging of the body and biological process is critical for diagnosing disease and personalizing treatment with the minimum side effects. Recently, diagnostic radiopharmaceuticals have gained more attention in precise molecular imaging due to their high sensitivity and appropriate tissue penetration depth. The fate of these radiopharmaceuticals throughout the body can be traced using nuclear imaging systems, including single-photon emission computed tomography (SPECT) and positron emission tomography (PET) modalities. In this regard, nanoparticles are attractive platforms for delivering radionuclides into targets because they can directly interfere with the cell membranes and subcellular organelles. Moreover, applying radiolabeled nanomaterials can decrease their toxicity concerns because radiopharmaceuticals are usually administrated at low doses. Therefore, incorporating gamma-emitting radionuclides into nanomaterials can provide imaging probes with valuable additional properties compared to the other carriers. Herein, we aim to review (1) the gamma-emitting radionuclides used for labeling different nanomaterials, (2) the approaches and conditions adopted for their radiolabeling, and (3) their application. This study can help researchers to compare different radiolabeling methods in terms of stability and efficiency and choose the best way for each nanosystem.

Commentary on prevention a possible drug-drug interaction: is concurrent administration of orlistat and pioglitazone increase the risk of durg-induced hepatotoxicity?

BACKGROUND: Drug-drug interactions (DDIs) are an emerging threat to public health and are difficult to detect. To prevent DDIs and their burden, the possible DDIs should be kept in mind. We know that the obesity predisposes to the development of insulin resistance and type 2 diabetes. Therefore, combinational uses of antiobesity drugs and glucose-lowering drugs are very common. As the hepatotoxicity of both pioglitazone (an antidiabetic drug) and orlistat (an antiobesity drug) has been shown in some cases, the aim of this study was to evaluate the interaction of pioglitazone and orlistat in human hepatocellular cell line human hepatocellular carcinoma (HepG2) cells to determine their effect on liver toxicity. METHODS: Human hepatocellular carcinoma cells were treated with 25 µM Pioglitazon (Pio), 20 µM Orlistat (Orl) pioglitazone, orlistat or combination of them. The MTT assay was used to assess cell viability. RESULTS: Pioglitazone and orlistat combination caused a loss of HepG2 cell viability. While pioglitazone (25 µM) and orliatat (20 µM) alone decreased the cell viability around 91% and 85% respectively (notsignificant, P > 0.05), the combination of these two drugs reduced the amount of viable cells to 55% which was significant when compared with each drug alone (P < 0.001). CONCLUSIONS: Revealing the significant loss of viability of HepG2 cells in the combination use of pioglitazone and orlistat indicates these two drugs should not be administered at the same time to prevent their hepatotoxic effects especially in patients with liver dysfunction.