Development and Characterization of Multifunctional Nanoparticles for Drug Delivery to Cancer Cells

Lipid and polymeric nanoparticles, although proven to be effective drug delivery systems compared to free drugs, have shown considerable limitations pertaining to their uptake and release at tumor sites. Spatial and temporal control over the delivery of anticancer drugs has always been challenge to drug delivery scientists. Here, we have developed and characterized multifunctional nanoparticles (liposomes and polymersomes) which are targeted specifically to cancer cells, and release their contents with tumor specific internal triggers. To enable these nanoparticles to be tracked in blood circulation, we have imparted them with echogenic characteristic. Echogenicity of nanoparticles is evaluated using ultrasound scattering and imaging experiments. Nanoparticles demonstrated effective release with internal triggers such as elevated levels of MMP-9 enzyme found in the extracellular matrix of tumor cells, decreased pH of lysosome, and differential concentration of reducing agents in cytosol of cancer cells. We have also successfully demonstrated the sensitivity of these particles towards ultrasound to further enhance the release with internal triggers. To ensure the selective uptake by folate receptor- overexpressing cancer cells, we decorated these nanoparticles with folic acid on their surface. Fluorescence microscopic images showed significantly higher uptake of folate-targeted nanoparticles by MCF-7 (breast cancer) and PANC-1 (pancreatic cancer) cells compared to particles without any targeting ligand on their surface. To demonstrate the effectiveness of these nanoparticles to carry the drugs inside and kill cancer cells, we encapsulated doxorubicin and/or gemcitabine employing the pH gradient method. Drug loaded nanoparticles showed significantly higher killing of the cancer cells compared to their non-targeted counterparts and free drugs. With further development, these nanoparticles certainly have potential to be used as a multifunctional nanocarriers for image guided, targeted delivery of anticancer drugs

Structural, optical and gas sensing properties of barium titanate surface modified by nano silver

Paper represents the results of SO2 sensing performance of BaTiO3 surface modified by nano silver. Surface modification was performed by dipping of BaTiO3 thick films in the synthesized nano silver. The main objective was to investigate the effect of nano silver on gas sensing performance of BaTiO3 perovskite. Different intervals of dipping time were used to find the optimum dipping amount on the surface of perovskite oxide. Synthesized silver was characterized by UV-visible spectroscopy and transmission electron microscopy. Surface modified thick films were analyzed for structural, morphological, electrical and gas sensing properties by XRD, SEM with EDX, static gas sensing unit respectively. Selectivity of surface modified BaTiO3 thick films was also investigated

Valsartan (Profiles of Drugs Substances, Excipients and Related Methodology)

Valsartan is an antihypertensive drug which selectively inhibits angiotensin receptor type II. This tetrazole derivative was first developed by Novartis and marketed under brand name Diovan® . This compound is orally active and is rapidly absorbed after oral doses, having a bioavailability of approximately 23% . Valsartan appears as a white or almost white hygroscopic powder. This compound must be kept in an air-tight container and should be protected from light and heat. It is available in film-coated tablets containing valsartan 40, 80, 160, or 320 mg, and capsules with dosage of 80 or 160 mg. Tablet combinations of valsartan with hydrochlorothiazide or amlodipine are also availabl

Neuroprotective effect of Cubebin: A dibenzylbutyrolactone lignan on scopolamine-induced amnesia in mice

Background & objectives: Acetylcholinesterase (AChE) inhibitors represent a major class of drugs which provide symptomatic relief and improvement in cognitive function in Alzheimer's disease (AD). In this study, cubebin, a dibenzylbutyrolactone lignan, was isolated from Piper cubeba and investigated for its AChE inhibitory activity in an attempt to explore its potential for memory-enhancing activities in mice. Methods: Molecular docking of cubebin was carried out followed by in vitro AChE activity. Mice were treated with cubebin (25 & 50 mg/kg; i.p.), for three days and memory impairment was induced by scopolamine (3 mg/kg; i.p.). Memory function was evaluated by Morris water maze (MWM) test. Biochemical parameters of oxidative stress and cholinergic function were estimated in brain. Results: Molecular docking study revealed that cubebin was well bound within the binding site of the AChE enzyme showing interactions such as π-π stacking and hydrogen bonding with residues present therein. Cubebin inhibited AChE enzyme in an in vitro assay with IC50value of 992 μM. Scopolamine administration caused a significant impairment of learning and memory in mice, as indicated by a marked decrease in MWM performance. Scopolamine administration also produced a significant enhancement of brain AChE activity and oxidative stress in mice brain. Pre-treatment of cubebin (25 and 50 mg/kg; i.p.) significantly prevented scopolamine-induced learning and memory deficits along with attenuation of scopolamine-induced rise in brain AChE activity and oxidative stress level. Interpretation & conclusions: Cubebin showed promising protective activity in scopolamine-induced spatial memory impairment in mice. This could be attributed to its brain AChE inhibition and antioxidant activity

Fine and Clean Photothermally Controlled NIR Drug Delivery from Biocompatible Nickel-bis(dithiolene)-Containing Liposomes

International audienceThis work demonstrates that metal-bis(dithiolene) complexes can be efficiently incorporated inside organic nanocarriers and, that under near-infrared (NIR) irradiation, their high photothermal activity can be finely used to release encapsulated drugs on demand. In contrast to gold nanoparticles and other organic NIR dyes, nickel-bis(dithiolene) complexes do not produce singlet oxygen under irradiation, a highly desirable characteristic to preserve the chemical integrity and activity of the loaded drug during the NIR-triggered release from the nanocarriers. Finally, cytotoxicity experiments performed on various cell lines have shown that the incorporation of such metal complexes do not increase the toxicity of the final liposomal formulation. These results offer great promise for the development of innovative biocompatible drug nanocargos that are able to safely deliver their content on demand under NIR laser irradiation. Moreover, this work demonstrates that metal-bis(dithiolene) complexes, owing to their versatility of functionalization and metal complexation, are attractive photothermal agents for the development of original NIR-responsive materials for application not only in biotechnology but also in materials science