A novel pH-sensitive liposome formulation containing oleyl alcohol

AbstractpH-sensitive liposomes are designed to undergo acid-triggered destabilization. First generation pH-sensitive liposomes, based on the cone-shaped lipid dioleoylphosphatidylethanolamine (DOPE), have been shown to lose fusogenicity in the presence of serum. Here, we report the design and evaluation of novel serum-resistant pH-sensitive liposome formulations that are based on the composition of egg phosphatidylcholine (PC), cholesteryl hemisuccinate (CHEMS), oleyl alcohol (OAlc), and Tween-80 (T-80). When loaded with the fluorescent probe calcein, these liposomes exhibited excellent stability at pH 7.4 and underwent rapid destabilization upon acidification as shown by calcein dequenching and particle size increase. Adjusting the mole percentages of T-80 and OAlc in the formulation could regulate the stability and pH-sensitive properties of these liposomes. Liposomes with a higher T-80 content exhibited greater stability but were less sensitive to acid-induced destabilization. Meanwhile, formulations with a higher OAlc content exhibited greater content release in response to low pH. The pH-triggered liposomal destabilization did not produce membrane fusion according to an octadecylrhodamine B chloride (R18) lipid-mixing assay. Compared to DOPE-based pH-sensitive liposomes, the above formulations showed much better retention of their pH-sensitive properties in the presence of 10% serum. These liposomes were then evaluated for intracellular delivery of entrapped cytosine-β-d-arabinofuranoside (araC) in KB human oral cancer cells, which have elevated folate receptor (FR) expression. The FR, which is amplified in many types of human tumors, has been shown to mediate the internalization of folate-derivatized liposomes into an acidic intracellular compartment. FR-targeted OAlc-based pH-sensitive liposomes, entrapping 200 mM araC, showed ∼17-times greater FR-dependent cytotoxicity in KB cells compared to araC delivered via FR-targeted non-pH-sensitive liposomes. These data indicated that pH-sensitive liposomes based on OAlc, combined with FR-mediated targeting, are promising delivery vehicles for membrane impermeable therapeutic agents

Additional file 1: of A systematic investigation of the maximum tolerated dose of cytotoxic chemotherapy with and without supportive care in mice

Additional information regarding the clinical severity score used to determine wellbeing of the mice and a comprehensive list of the chemotherapeutic drugs used in this study. (PDF 82 kb

Additional file 1: Table S1. of Consistent gene expression profiles in MexTAg transgenic mouse and wild type mouse asbestos-induced mesothelioma

PCR primers. (DOCX 23 kb

La Charente

06 janvier 18821882/01/06 (A11,N4538)-1882/01/06.Appartient à l’ensemble documentaire : PoitouCh

Additional file 3: Figure S3. of Evaluating the effectiveness of IV iron dosing for anemia management in common clinical practice: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS)

Distribution of 3-month IV iron dose. (PPTX 546 kb

El Diario de Pontevedra : periódico liberal: Ano XXXV Número 10236 - 1918 maio 22

Genes of interest previously reported in MM and primer sequences used to detect expression of the targets in murine messenger RNA. (DOCX 85 kb

Additional file 2: Table S1. of Analysis of SDHAF3 in familial and sporadic pheochromocytoma and paraganglioma

Summary of SDHAF3 c.157 T > C (p.Phe53Leu) variant analysis in familial SDH-associated individuals. Twenty-three unrelated individuals with SDH germline mutations and evidence of disease (i.e. presence of pheochromocytoma and/or paraganglioma) were assessed (using massively parallel sequencing and/or Sanger sequencing) for the presence of SDHAF3 c.157 T > C. (PDF 236 kb

Additional file 1: Table S2. of Analysis of SDHAF3 in familial and sporadic pheochromocytoma and paraganglioma

Summary of SDHAF3 c.157 T > C (p.Phe53Leu) variant analysis in pheochromocytoma and/or paraganglioma of suspected sporadic origin. Fifteen pheochromoctyomas and/or paragangliomas of apparently sporadic origin were assessed (using massively parallel sequencing and/or Sanger sequencing) for the presence of SDHAF3 c.157 T > C. (PDF 119 kb

Data File 1: Harnessing nonlinearities near material absorption resonances for reducing losses in plasmonic modulators

Refractive Index of 75%HD-BB-OH and 25%YLD124 Originally published in Optical Materials Express on 01 July 2017 (ome-7-7-2168

Additional file 1: Figure S1. of Calretinin as a blood-based biomarker for mesothelioma

Comparison of marker concentrations in different non-MM pathologies. All controls of group 1, 2, and 3 were pooled and then separated into plaques, asbestosis plus plaques, and asbestosis. P-values for each comparison between the three pathologies are indicated. (A) Concentrations of Calretinin [ng/mL] and (B) Mesothelin [nmol/L]. P-values for calretinin were obtained from two-sided Peto-Prentice test and for mesothelin from two-sided Wilcoxon rank-sum test. (TIFF 380 kb