Evaluation of the Mucoadhesive Properties of Chitosan-Based Microstructured Lipid Carrier (CH-MLC)

Different mucoadhesive systems have been studied in recent years to increase the residence time of the delivery systems and to prolong the release of the drug. The aim of this work was to evaluate the mucoadhesive properties of chitosan-based Microstructured Lipid Carrier (CH-MLC) with a new approach which requires chitosan and mucin to be compacted into a tablet and mucoadhesion to be assessed on a non-mucoadhesive substrate. This type of test showed that chitosan maintains a close bond with mucin even in the presence of a fluid and even encapsulated in microparticles. After this, using a bioreactor, the release of N-acetylcysteine (NAC) from the microparticles (NA-CH-MLC) through a layer of mucus mimicking the pathological conditions of a patient with cystic fibrosis was tested. The release of the active from NAC-CH-MLC demonstrated how the chitosan inside the microparticles acts as a penetration enhancer and how the microparticles can impart a prolonged release over time.

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The Role Of Mexxy Efflux Pump Expression In The Development Of Aminoglycoside Resistance In P. Aeruginosa Over Time In Patients With Cystic Fibrosis

10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a4864 ◽

2011 ◽

Author(s):

Michelle Prickett ◽

Alan R. Hauser ◽

Susanna McColley ◽

Joanne Cullina ◽

Eileen Potter ◽

...

Keyword(s):

Cystic Fibrosis ◽

Efflux Pump ◽

Aminoglycoside Resistance ◽

Over Time

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National Healthcare Delivery Systems Influence Lung Transplant Outcomes for Cystic Fibrosis

American Journal of Transplantation ◽

10.1111/ajt.13226 ◽

2015 ◽

Vol 15 (7) ◽

pp. 1948-1957 ◽

Cited By ~ 15

Author(s):

C. A. Merlo ◽

S. C. Clark ◽

G. J. Arnaoutakis ◽

N. Yonan ◽

D. Thomas ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Transplant ◽

Healthcare Delivery ◽

Delivery Systems ◽

Transplant Outcomes ◽

National Healthcare ◽

Healthcare Delivery Systems

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Change in Pseudomonas aeruginosa prevalence in cystic fibrosis adults over time

BMC Pulmonary Medicine ◽

10.1186/s12890-016-0333-y ◽

2016 ◽

Vol 16 (1) ◽

Cited By ~ 22

Author(s):

Mathew R. Crull ◽

Kathleen J. Ramos ◽

Ellen Caldwell ◽

Nicole Mayer-Hamblett ◽

Moira L. Aitken ◽

...

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Over Time

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Natural history of glucose tolerance, beta-cell function and peripheral insulin sensitivity in cystic fibrosis patients with fasting euglycemia

Acta Endocrinologica ◽

10.1530/eje.0.1490053 ◽

2003 ◽

Vol 149 (1) ◽

pp. 53-59 ◽

Cited By ~ 58

Author(s):

F Lombardo ◽

F De Luca ◽

M Rosano ◽

C Sferlazzas ◽

C Lucanto ◽

...

Keyword(s):

Cystic Fibrosis ◽

Insulin Sensitivity ◽

Natural History ◽

Glucose Tolerance ◽

Pancreatic Beta Cells ◽

Cell Function ◽

Glucose Levels ◽

Peripheral Insulin Resistance ◽

History Of ◽

Over Time

OBJECTIVE: The loss of pancreatic beta-cells is thought to be one of the principal causes of diabetes mellitus (DM) in cystic fibrosis (CF), but the role of peripheral insulin resistance (IR) in the pathogenesis of DM in CF remains unclear. The aim of this study was to evaluate whether eventual changes of glucose tolerance (GT) over time were associated with modifications of insulin secretion or sensitivity. METHODS: Plasma glucose and insulin responses to an oral GT test (OGTT) were investigated and reinvestigated 13 Years later in 14 CF patients with initial and persistent fasting euglycemia and no history of insulin treatment. Insulin sensitivity (IS) at both tests was assessed on the basis of insulin and glucose levels both in the fasting state and during OGTTs. RESULTS: From the 1st to the 2nd OGTT: (a) the prevalence of DM responses significantly increased; (b) the areas beneath the respective glucose and insulin curves significantly increased and decreased respectively; (c) IR and IS indices decreased and increased respectively, even in the patients who developed DM; (d) pulmonary function significantly worsened in the entire series, especially in the patients who developed DM. CONCLUSIONS: (i) the natural history of glyco-metabolic status in CF is characterized by deteriorating GT over time; (ii) insulinopenia plays a prominent role in the pathogenesis of GT worsening; (iii) IR does not play any significant part in the pathogenesis of DM development; (iv) deterioration of lung function tests is more severe in the subjects who develop DM over time.

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Serial Analysis of the Gut and Respiratory Microbiome in Cystic Fibrosis in Infancy: Interaction between Intestinal and Respiratory Tracts and Impact of Nutritional Exposures

mBio ◽

10.1128/mbio.00251-12 ◽

2012 ◽

Vol 3 (4) ◽

Cited By ~ 172

Author(s):

J. C. Madan ◽

D. C. Koestler ◽

B. A. Stanton ◽

L. Davidson ◽

L. A. Moulton ◽

...

Keyword(s):

Cystic Fibrosis ◽

Respiratory Tract ◽

Microbial Communities ◽

Effective Means ◽

Significant Proportion ◽

Gut Colonization ◽

Pulmonary Damage ◽

Chronic Colonization ◽

High Degree ◽

Over Time

ABSTRACT Pulmonary damage caused by chronic colonization of the cystic fibrosis (CF) lung by microbial communities is the proximal cause of respiratory failure. While there has been an effort to document the microbiome of the CF lung in pediatric and adult patients, little is known regarding the developing microflora in infants. We examined the respiratory and intestinal microbiota development in infants with CF from birth to 21 months. Distinct genera dominated in the gut compared to those in the respiratory tract, yet some bacteria overlapped, demonstrating a core microbiota dominated by Veillonella and Streptococcus. Bacterial diversity increased significantly over time, with evidence of more rapidly acquired diversity in the respiratory tract. There was a high degree of concordance between the bacteria that were increasing or decreasing over time in both compartments; in particular, a significant proportion (14/16 genera) increasing in the gut were also increasing in the respiratory tract. For 7 genera, gut colonization presages their appearance in the respiratory tract. Clustering analysis of respiratory samples indicated profiles of bacteria associated with breast-feeding, and for gut samples, introduction of solid foods even after adjustment for the time at which the sample was collected. Furthermore, changes in diet also result in altered respiratory microflora, suggesting a link between nutrition and development of microbial communities in the respiratory tract. Our findings suggest that nutritional factors and gut colonization patterns are determinants of the microbial development of respiratory tract microbiota in infants with CF and present opportunities for early intervention in CF with altered dietary or probiotic strategies. IMPORTANCE While efforts have been focused on assessing the microbiome of pediatric and adult cystic fibrosis (CF) patients to understand how chronic colonization by these microbes contributes to pulmonary damage, little is known regarding the earliest development of respiratory and gut microflora in infants with CF. Our findings suggest that colonization of the respiratory tract by microbes is presaged by colonization of the gut and demonstrated a role of nutrition in development of the respiratory microflora. Thus, targeted dietary or probiotic strategies may be an effective means to change the course of the colonization of the CF lung and thereby improve patient outcomes.

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Measuring Poverty in Britain as a Multi-dimensional Concept, 1991 to 2003

Journal of Social Policy ◽

10.1017/s0047279408002237 ◽

2008 ◽

Vol 37 (4) ◽

pp. 597-620 ◽

Cited By ~ 39

Author(s):

MARK TOMLINSON ◽

ROBERT WALKER ◽

GLENN WILLIAMS

Keyword(s):

Structural Equation Modelling ◽

Structural Equation ◽

Panel Study ◽

Financial Stress ◽

Material Deprivation ◽

New Approach ◽

Equation Modelling ◽

Dimensional Measure ◽

Trends Over Time ◽

Over Time

AbstractWhile poverty is widely accepted to be an inherently multi-dimensional concept, it has proved very difficult to develop measures that both capture this multi-dimensionality and facilitate comparison of trends over time. Structural equation modelling appears to offer a solution to this conundrum and is used to exploit the British Household Panel Study to create a multi-dimensional measure of poverty. The analysis reveals that the decline in poverty in Britain between 1991 and 2003 was driven by falls in material deprivation, but more especially by reduced financial stress, particularly during the early 1990s. The limitations and potential of the new approach are critically discussed.

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Logica di un sistema di sostegno alle imprese. La politica industriale italiana dal secondo dopoguerra a "Industria 2015"

Economia e Politica Industriale ◽

10.3280/poli2009-004006 ◽

2009 ◽

pp. 89-113

Author(s):

Fabrizio Traů

Keyword(s):

Industrial Policy ◽

State Intervention ◽

State Aid ◽

Limiting State ◽

New Approach ◽

Industrial Activities ◽

The Universe ◽

Over Time

- The paper aims at discussing the logic lying behind sixty years of industrial policy in Italy. It is argued that during this time State intervention has been characterised by the issue of an increasing number of laws (mostly persisting over time) devoted to specific objectives, but at the same time paralleled by a tendency towards the reduction of their selectivity through the widening (i.e. the loosening) of the boundaries of the universe of firms they were thought for. Such a logic seems to have made way in recent years for a relatively new approach, as stated in the program "Industria 2015", which has put at the centre of the stage the need for limiting State aid to a selected group of (horizontally identified) industrial activities. The paper also discusses some apparent shortcomings of this approach, emphasising that a risk for a new weakening of its selective logic is still at work.

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Towards feedback-controlled nanomedicines for smart, adaptive delivery

Experimental Biology and Medicine ◽

10.1177/1535370218800456 ◽

2018 ◽

Vol 244 (4) ◽

pp. 283-293 ◽

Cited By ~ 4

Author(s):

Stephen J. Jones ◽

Annette F. Taylor ◽

Paul A Beales

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Drug Delivery Systems ◽

Delivery Systems ◽

The Body ◽

Living Systems ◽

Prolonged Release ◽

Drug Bioavailability ◽

Drug Release Profile ◽

Chemical Systems

Nanomedicines for controlled drug release provide temporal and spatial regulation of drug bioavailability in the body. The timing of drug release is usually engineered either for slow gradual release over an extended period of time or for rapid release triggered by a specific change in its physicochemical environment. However, between these two extremes, there is the desirable possibility of adaptive nanomedicines that dynamically modulate drug release in tune with its changing environment. Adaptation and response through communication with its environment is a fundamental trait of living systems; therefore, the design of biomimetic nanomedicines through the approaches of bottom-up synthetic biology provides a viable route to this goal. This could enable drug delivery systems to optimize release in synchronicity with the body’s natural biological rhythms and the personalized physiological characteristics of the patient, e.g. their metabolic rate. Living systems achieve this responsiveness through feedback-controlled biochemical processes that regulate their functional outputs. Towards this goal of adaptive drug delivery systems, we review the general benefits of nanomedicine formulations, provide existing examples of experimental nanomedicines that encapsulate the metabolic function of enzymes, and give relevant examples of feedback-controlled chemical systems. These are the underpinning concepts that hold promise to be combined to form novel adaptive release systems. Furthermore, we motivate the advantages of adaptive release through chronobiological examples. By providing a brief review of these topics and an assessment of the state of the art, we aim to provide a useful resource to accelerate developments in this field. Impact statement The timing and rate of release of pharmaceuticals from advanced drug delivery systems is an important property that has received considerable attention in the scientific literature. Broadly, these mostly fall into two classes: controlled release with a prolonged release rate or triggered release where the drug is rapidly released in response to an environmental stimulus. This review aims to highlight the potential for developing adaptive release systems that more subtlety modulate the drug release profile through continuous communication with its environment facilitated through feedback control. By reviewing the key elements of this approach in one place (fundamental principles of nanomedicine, enzymatic nanoreactors for medical therapies and feedback-controlled chemical systems) and providing additional motivating case studies in the context of chronobiology, we hope to inspire innovative development of novel “chrononanomedicines.”

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Influence of Oleic Acid on the Rheology and in Vitro Release of Lumiracoxib from Poloxamer Gels

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/j34880 ◽

2010 ◽

Vol 13 (2) ◽

pp. 286 ◽

Cited By ~ 13

Author(s):

Tailane Sant´Anna Moreira ◽

Valéria Pereira De Sousa ◽

Maria Bernadete Riemma Pierre

Keyword(s):

Oleic Acid ◽

Rheological Behavior ◽

Transdermal Delivery ◽

In Vitro Release ◽

Delivery Systems ◽

Penetration Enhancer ◽

Release Studies ◽

Vitro Release ◽

Gel Transition

Abstract PURPOSE: Transdermal delivery of anti-inflammatory lumiracoxib (LM) could be an interesting strategy to avoid the side effects associated with systemic delivery, but it is ineffective due to the drug poor skin penetration. We have investigated the effects of oleic acid (OA), a lipid penetration enhancer, on the in vitro release of LM from poloxamer-based delivery systems (PBDS). The rheological behavior (shear rate dependent viscosity) and gelation temperature through measurements of optimal sol-gel transition temperatures (Tsol-gel) were also carried out in these systems. METHODS: In vitro release studies of LM from PBDS were performed using cellulose acetate as artificial membrane mounted in a diffusion system. The amount of LM released was divided by exposition area (µg/cm2) and these values were plotted as function of the time (h). The flux of the drug across the membrane (J) was calculated from the slope of the linear portion of the plot and expressed as µg/cm2. h -1. The determination of viscosity was carried out at different shear rates (γ) between 0.1- 1000 S-1 using a parallel plate rheometer. Oscillatory measurements using a cone-plate geometry rheometer surrounded by a double jacket with temperature varying 4-40°C, was used in order to determine Tsol-gel. RESULTS: Increase of both polymer and OA concentrations increases the viscosity of the gels and consequently reduces the in vitro LM release from the PBDS, mainly for gels containing OA at 10.0% compared to other concentrations of the penetration enhancer. Tsol-gel transition temperature was decreased by increasing viscosity; in some cases the formulation was already a gel at room temperature. Rheological studies showed a pseudoplastic behavior, which facilitates the flow and improves the spreading characteristics of the formulations. CONCLUSIONS: Taken together, the results showed that poloxamer gels are good potential delivery systems for LM, leading to a sustained release, and also have appropriate rheological characteristics. Novelty of the work: A transdermal delivery of non-steroidal antinflammatory drugs like lumiracoxib (LM) can be an interesting alternative to the oral route of this drug, since it was recently withdraw of the market due to the liver damage when systemically administered in tablets as dosage form. There are no transdermal formulations of LM and it could be an alternative to treat inflammation caused by arthritis or arthrosis. Then, an adequate delivery system to LM is necessary in order to release the drug properly from the PBDS as well as have good characteristics related to semi-solid preparations for transdermal application, which were evaluated through in vitro release studies and rheological behavior in this paper, respectively.

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