The role of glutathione conjugation on the transcellular transport process of PEGylated liposomes across the blood brain barrier.

Notwithstanding the growing evidence of improved drug delivery efficiency to the brain by ligand modification of PEGylated liposomes, the comprehensive knowledge of their transport processes and payload across the BBB is yet to be revealed. Herein, this study sought to understand the glutathione (GSH) ligand effect on transcellular transport mechanisms of liposomes through the blood-brain barrier (BBB) by comparing PEGylated liposomes (PEG-L) and GSH PEGylated liposomes (GSH-PEG-L). Endocytosis and exocytosis of liposomes including the role of secreted extracellular vesicles (EVs) of brain endothelial cells (BECs) were assessed.

The involvement of extracellular vesicles in the transcytosis of nanoliposomes through brain endothelial cells, and the impact of liposomal pH-sensitivity.

Despite the demonstrated effectiveness of nano-materials for drug delivery to the brain, a comprehensive understanding of their transport processes across the blood brain barrier (BBB) remains undefined. This multidisciplinary study aimed to gain an insight into the transport processes across BBB, focusing on the transcytosis of liposomes and the impact of liposomal pH-sensitivity. Glutathione-PEGylated pH-sensitive (GSH-PEG-pSL) and non pH-sensitive liposomes (GSH-PEG-L) were fluorescently labelled with rhodamine-DOPE and calcein, both impermeable to biomembranes.

Zebularine suppressed gemcitabine-induced senescence and improved the cellular and plasma pharmacokinetics of gemcitabine, augmented by liposomal co-delivery.

Chemoresistance is a major factor driving cancer recurrence. This study investigated the potential of zebularine, a dual cytidine deaminase (CDA)/epigenetic inhibitor, to circumvent gemcitabine-resistance in pancreatic cancer using a nanomedicine co-delivery approach. The mRNA expression of key metabolic enzymes, including CDA for gemcitabine deactivation in a gemcitabine-resistant cell line Gr2000 and its parental MIA PaCa-2 was compared using quantitative reverse transcription polymerase chain reaction.

Optimisation of glutathione conjugation to liposomes quantified with a validated HPLC assay.

Glutathione (GSH) grafted onto nanoliposomes (GSH-liposomes) have the potential to enhance drug delivery into the brain. GSH is known to be an unstable tripeptide, however, despite widespread use to promote active transport its stability has been largely ignored to date. Therefore this study focuses on the optimisation of GSH conjugation with liposomes, supported with a validated HPLC assay for GSH.

Molecular interaction between glimepiride and Soluplus®-PEG 4000 hybrid based solid dispersions: Characterisation and anti-diabetic studies.

The objective of this study was to evaluate a novel blend of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol 6000 grafted copolymer (Soluplus®) and polyethylene glycol (PEG) 4000 for solubility enhancement, physicochemical stability and anti-diabetic efficacy of the produced solid dispersions containing glimepiride, a biopharmaceutics classification system (BCS) class II sulphonylurea. Different batches of glimepiride solid dispersions (SD) were prepared by the solvent evaporation method using the individual polymers and blends of the polymers at different ratios. The Soluplus®-PEG 4000 (sol-PEG) hybrid polymer based glimepiride solid dispersions were characterized by differential scanning calorimetry (DSC), fourier transform infrared (FTIR) spectroscopy, micromeritics and dissolution studies.

Cyclic-AMP agonists inhibit antiphospholipid/beta2-glycoprotein I induced synthesis of human platelet thromboxane A2 in vitro.

Objective: To investigate mechanisms responsible for increased thrombotic activity in systemic lupus erythematosus (SLE) associated with the antiphospholipid syndrome (APS). We had reported that anticardiolipin/beta2-glycoprotein I (aCL/beta2-GPI) complexes induce platelet overactivity resulting in excessive production of thromboxane A2 (TXA2). Presumably this occurs by decreased platelet cyclic AMP (cAMP) activity and results in increased platelet aggregation.