42 research outputs found
Potential of a cyclone prototype spacer to improve in vitro dry powder delivery
Copyright The Author(s) 2013. This article is published with open access at Springerlink.com. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are creditedPurpose: Low inspiratory force in patients with lung disease is associated with poor deagglomeration and high throat deposition when using dry powder inhalers (DPIs). The potential of two reverse flow cyclone prototypes as spacers for commercial carrierbased DPIs was investigated. Methods: Cyclohaler®, Accuhaler® and Easyhaler® were tested with and without the spacers between 30-60 Lmin-1. Deposition of particles in the next generation impactor and within the devices was determined by high performance liquid chromatography. Results: Reduced induction port deposition of the emitted particles from the cyclones was observed due to the high retention of the drug within the spacers (e.g. salbutamol sulphate (SS): 67.89 ± 6.51 % at 30 Lmin-1 in Cheng 1). Fine particle fractions of aerosol as emitted from the cyclones were substantially higher than the DPIs alone. Moreover, the aerodynamic diameters of particles emitted from the cyclones were halved compared to the DPIs alone (e.g. SS from the Cyclohaler® at 4 kPa: 1.08 ± 0.05 μm vs. 3.00 ± 0.12 μm, with and without Cheng 2, respectively) and unaltered with increased flow rates. Conclusion: This work has shown the potential of employing a cyclone spacer for commercial carrier-based DPIs to improve inhaled drug delivery.Peer reviewe
The histone deacetylase inhibitor trichostatin A downregulates human MDR1 (ABCB1) gene expression by a transcription-dependent mechanism in a drug-resistant small cell lung carcinoma cell line model
Tumour drug-resistant ABCB1 gene expression is regulated at the chromatin level through epigenetic mechanisms. We examined the effects of the histone deacetylase inhibitor trichostatin A (TSA) on ABCB1 gene expression in small cell lung carcinoma (SCLC) drug-sensitive (H69WT) or etoposide-resistant (H69VP) cells. We found that TSA induced an increase in ABCB1 expression in drug-sensitive cells, but strongly decreased it in drug-resistant cells. These up- and downregulations occurred at the transcriptional level. Protein synthesis inhibition reduced these modulations, but did not completely suppress them. Differential temporal patterns of histone acetylation were observed at the ABCB1 promoter: increase in H4 acetylation in both cell lines, but different H3 acetylation with a progressive increase in H69WT cells but a transient one in H69VP cells. ABCB1 regulations were not related with the methylation status of the promoter −50GC, −110GC, and Inr sites, and did not result in further changes to these methylation profiles. Trichostatin A treatment did not modify MBD1 binding to the ABCB1 promoter and similarly increased PCAF binding in both H69 cell lines. Our results suggest that in H69 drug-resistant SCLC cell line TSA induces downregulation of ABCB1 expression through a transcriptional mechanism, independently of promoter methylation, and MBD1 or PCAF recruitment
A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome
Down syndrome, caused by an extra copy of chromosome 21, is associated with a greatly increased risk of early onset Alzheimer disease. It is thought that this risk is conferred by the presence of three copies of the gene encoding amyloid precursor protein (APP), an Alzheimer risk factor, although the possession of extra copies of other chromosome 21 genes may also play a role. Further study of the mechanisms underlying the development of Alzheimer disease in Down syndrome could provide insights into the mechanisms that cause dementia in the general population
LIPOSOMES AS AN IMMUNOADJUVANT SYSTEM FOR STIMULATION OF MUCOSAL AND SYSTEMIC ANTIBODY-RESPONSES AGAINST INACTIVATED MEASLES-VIRUS ADMINISTERED INTRANASALLY TO MICE
This paper reports on the immune-stimulatory activity of liposomes in an inactivated whole measles virus vaccine preparation administered intranasally to mice. Liposomes, simply mixed with inactivated whole measles virus, significantly stimulated the serum IgG response relative to the response to the virus alone. In addition, the liposomal vaccine, but not the free virus induced a secretory IgA (s-IgA) response in the lungs and nasal cavity. Serum IgG and s-IgA responses persisted up to at least 24 weeks post-immunization. The liposomes induced a moderate increase in the serum IgG response, but no s-IgA response, following intramuscular immunization. It is concluded that liposomes provide a promising adjuvant system for induction of high systemic as well as mucosal antibody responses against inactivated measles virus in an intranasal Or inhalation vaccine formulation
MUCOSAL IMMUNOADJUVANT ACTIVITY OF LIPOSOMES - INDUCTION OF SYSTEMIC IGG AND SECRETORY IGA RESPONSES IN MICE BY INTRANASAL IMMUNIZATION WITH AN INFLUENZA SUBUNIT VACCINE AND COADMINISTERED LIPOSOMES
This paper reports on a novel immunonadjuvant activity of liposomes. An influenza subunit preparation, containing the isolated viral surface antigens, was incorporated in a liposomal formulation. Administration of this vaccine to mice via the intranasal (i.n.) route resulted in a stimulated serum IgG response relative to the response to i.n. immunization with the antigen alone. In addition, the liposomal vaccine induced a secretory IgA (sIgA) response in the mucosa of the lungs and nasal cavity. Both serum IgG and sIgA responses persisted up to at least 21, weeks postimmmunization. Immune stimulation was ns observed with negatively charged liposomes consisting of phosphatidylcholine (PC), cholesterol and dicetylphosphate (DCP), but not with zwitterionic liposomes, consisting of PC and cholesterol alone. Remarkably, for stimulation of serum IgG responses and induction of an sIgA response, liposomes could be simply mixed with the antigen. Moreover, i.n. administration of empty liposomes up to 48 h prior to i.n. immunization with the subunit antigen also resulted in immune stimulation, indicating that the liposomes did not exert their adjuvant effect by acting as a carrier for the antigen. The liposomal vaccine conferred protection against infection. It is concluded that liposomes, administered i.n., provide a promising adjuvant system for stimulation of antibody responses in general, and mucosal sIgA responses in particular