Radioiodination and bioevaluation of rolipram as a tracer for brain imaging: In silico study,molecular modeling and gamma scintigraphy

Brain imaging is considered one of the most fruitful applications of radioisotope scanning. Rolipram, a selective phospodiesterase‐4 inhibitor, has been labeled using [¹²⁵I] with chloramine‐T (Ch‐T) as an oxidizing agent. Factors, such as the amount of substrate, pH, the amount of oxidizing agent, temperature, and the reaction time, have been systematically studied to optimize the iodination process. In addition, bio‐distribution studies have indicated that the brain uptake of [¹²⁵I]iodorolipram is 7.6 ± 0.33 injected dose/g organ at 10 minutes post‐injection, which cleared from the brain with time until it reaches 1.30 ± 0.17% at 1 hour post‐injection. Therefore, iodorolipram could be considered as a potential, new selective radiotracer for brain imaging.     

Demonstration of pharmaceutical tablet coating process by injection molding technology

We demonstrate the coating of tablets using an injection molding (IM) process that has advantage of being solvent free and can provide precision coat features. The selected core tablets comprising 10% w/w griseofulvin were prepared by an integrated hot melt extrusion-injection molding (HME-IM) process. Coating trials were conducted on a vertical injection mold machine. Polyethylene glycol and polyethylene oxide based hot melt extruded coat compositions were used. Tablet coating process feasibility was successfully demonstrated using different coating mold designs (with both overlapping and non-overlapping coatings at the weld) and coat thicknesses of 150 and 300?μm. The resultant coated tablets had acceptable appearance, seal at the weld, and immediate drug release profile (with an acceptable lag time). Since IM is a continuous process, this study opens opportunities to develop HME-IM continuous processes for transforming powder to coated tablets.     

Lipid nanocarriers as skin drug delivery systems: Properties,mechanisms of skin interactions and medical applications

During the past decades, lipid nanocarriers are gaining momentum with their multiple advantages for the management of skin diseases. Lipid nanocarriers enable to target the therapeutic payload to deep skin layers or even to reach the blood circulation making them a promising cutting-edge technology.Lipid nanocarriers refer to a large panel of drug delivery systems. Lipid vesicles are the most conventional, known to be able to carry lipophilic and hydrophilic active agents. A variety of lipid vesicles with high flexibility and deformability could be obtained by adjusting their composition; namely ethosomes, transfersomes and penetration enhancer lipid vesicles which achieve the best results in term of skin permeation. Others are designed with the objective to perform higher encapsulation rate and higher stability, such as solid lipid nanoparticles and nanostructured lipid nanocarriers.In this review, we attempted to give an overview of lipid based nanocarriers developed with the aim to enhance dermal and transdermal drug delivery. A special focus is put on the nanocarrier composition, behavior and interaction mechanisms with the skin. Recent applications of lipid-based nanocarriers for the management of skin diseases and other illnesses are highlighted as well.     

Enhanced in vitro activity of tigecycline in the presence of chelating agents

The lack of availability of novel antibiotic agents and the rise of resistance to existing therapies has led clinicians to utilise combination therapy to adequately treat bacterial infections. Here we examined how chelators may impact the in vitro activity of tigecycline (TIG) against Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae. Minimum inhibitory concentrations (MICs) were determined by broth dilution with and without various combinations of chelators (EDTA and other tetracyclines) and metal ions (i.e. calcium, magnesium). Trimethoprim (TMP) was used as a non-chelating control. Addition of metal ions led to increases in MICs, whilst addition of EDTA led to decreases in MICs. The chelating effects of EDTA were reversed by addition of magnesium and most profoundly calcium. Similar effects of EDTA and calcium were observed for tetracycline (TET) and TMP. When other tetracyclines (TET, oxytetracycline (OXY) and chlortetracycline (CHL)) were used as chelators at concentrations below their MICs, TIG MICs decreased for P. aeruginosa but not for E. coli. Some decreases in TIG MICs were observed for K. pneumoniae when TET and CHL were added. A dose-dependent decrease in TIG MIC was observed for TET and was reversed by the addition of calcium. The presence of effects of EDTA and calcium on TMP MICs indicates that mechanisms outside of TIG chelation likely play a role in enhanced activity. Full characterisation of an unexpected interaction such as TIG–TET with different microorganisms could provide valuable insights into the underlying mechanisms and design of physiologically viable chelators as candidates for future combinations regimens.     

Second generation antipsychotic-induced mitochondrial alterations: Implications for increased risk of metabolic syndrome in patients with schizophrenia

Metabolic syndrome (MetS) is seen more frequently in persons with schizophrenia than in the general population, and these metabolic abnormalities are further aggravated by second generation antipsychotic (SGA) drugs. Although the underlying mechanisms responsible for the increased prevalence of MetS among patients under SGA treatment are not well understood, alterations in mitochondria function have been implicated. We performed a comprehensive evaluation of the role of mitochondrial dysfunction in the pathophysiology of drug-induced MetS in schizophrenia. We found a downregulation in genes encoding subunits of the electron transport chain complexes (ETC), enzyme activity, and mitochondrial dynamics in peripheral blood cells from patients at high-risk for MetS. Additionally, we evaluated several markers of energy metabolism in lymphoblastoid cell lines from patients with schizophrenia and controls following exposure to antipsychotics. We found that the high-risk drugs clozapine and olanzapine induced a general down-regulation of genes involved in the ETC, as well as decreased activities of the corresponding enzymes, ATP levels and a significant decrease in all the functional parameters of mitochondrial oxygen consumption in cells from patients and controls. We also observed that the medium-risk SGA quetiapine decreased oxygen consumption and respiratory control ratio in controls and patients. Additionally, clozapine and olanzapine induced a downregulation of Drp1 and Mfn2 both in terms of mRNA and protein levels. Together, these data suggest that an intrinsic defect in multiple components of oxidative metabolism may contribute to the increased prevalence of MetS in patients under treatment with SGAs known to cause risk for MetS.