Aline Gillet

Skin penetration behaviour of liposomes as a function of their composition.

Deformable liposomes have been developed and evaluated as a novel topical and transdermal delivery system. Their mechanism of drug transport into and through the skin has been investigated but remains a much debated question. The present study concerns ex vivo diffusion experiments using pig ear skin in order to explain the penetration mechanism of classical and deformable liposomes. Classical and deformable vesicles containing betamethasone in the aqueous compartment through the use of cyclodextrin inclusion complexes were compared to vesicles encapsulating betamethasone in their lipid bilayer. Deformable liposomes contained sodium deoxycholate as the edge activator. Liposomes were characterised by their diameter, encapsulation efficiency, deformability, stability (in terms of change in diameter) and release of encapsulated drug. Ex vivo diffusion studies using Franz diffusion cells were performed. Confocal microscopy was performed to visualise the penetration of fluorescently labelled liposomes into the skin. This study showed that liposomes do not stay intact when they penetrate the deepest layers of the skin. Betamethasone is released from the vesicles after which free drug molecules can diffuse through the stratum corneum and partition into the viable skin tissue.

Development of a new topical system: Drug-in-cyclodextrin-in-deformable liposome

A new delivery system for cutaneous administration combining the advantages of cyclodextrin inclusion complexes and those of deformable liposomes was developed, leading to a new concept: drug-in-cyclodextrin-in-deformable liposomes. Deformable liposomes made of soybean phosphatidylcholine (PC) or dimyristoylphosphatidylcholine (DMPC) and sodium deoxycholate as edge activator were compared to classical non-deformable liposomes. Liposomes were prepared by the film evaporation method. Betamethasone, chosen as the model drug, was encapsulated in the aqueous cavity of liposomes by the use of cyclodextrins. Cyclodextrins allow an increase in the aqueous solubility of betamethasone and thus, the encapsulation efficiency in liposome vesicles. Liposome size, deformability and encapsulation efficiency were calculated. The best results were obtained with deformable liposomes made of PC in comparison with DMPC. The stability of PC vesicles was evaluated by measuring the leakage of encapsulated calcein on the one hand and the leakage of encapsulated betamethasone on the other hand. In vitro diffusion studies were carried out on Franz type diffusion cells through polycarbonate membranes. In comparison with non-deformable liposomes, these new vesicles showed improved encapsulation efficiency, good stability and higher in vitro diffusion percentages of encapsulated drug. They are therefore promising for future use in ex vivo and in vivo experiments.

Liposome surface charge influence on skin penetration behaviour

Vesicular systems have shown their ability to increase dermal and transdermal drug delivery. Their mechanism of drug transport into and through the skin has been investigated but remains a much debated question. Several researchers have outlined that drug penetration can be influenced by modifying the surface charge of liposomes. In the present work we study the influence of particle surface charge on skin penetration. The final purpose is the development of a carrier system which is able to enhance the skin delivery of two model drugs, betamethasone and betamethasone dipropionate. Liposomes were characterised by their size, morphology, zeta potential, encapsulation efficiency and stability. Ex vivo diffusion studies using Franz diffusion cells were performed. Confocal microscopy was performed to visualise the penetration of fluorescently labelled liposomes into the skin. This study showed the potential of negatively charged liposomes to enhance the skin penetration of betamethasone and betamethasone dipropionate.

Nuclear delivery of a therapeutic peptide by long circulating pH-sensitive liposomes: Benefits over classical vesicles

The purpose of this study is to propose a suitable vector combining increased circulation lifetime and intracellular delivery capacities for a therapeutic peptide. Long circulating classical liposomes [SPC:CHOL:PEG-750-DSPE (47:47:6 molar% ratio)] or pH-sensitive stealth liposomes [DOPE:CHEMS:CHOL:PEG(750)-DSPE (43:21:30:6 molar% ratio)] were used to deliver a therapeutic peptide to its nuclear site of action. The benefit of using stealth pH-sensitive liposomes was investigated and formulations were compared to classical liposomes in terms of size, shape, charge, encapsulation efficiency, stability and, most importantly, in terms of cellular uptake. Confocal microscopy and flow cytometry were used to evaluate the intracellular fate of liposomes themselves and of their hydrophilic encapsulated material. Cellular uptake of peptide-loaded liposomes was also investigated in three cell lines: Hs578t human epithelial cells from breast carcinoma, MDA-MB-231 human breast carcinoma cells and WI-26 human diploid lung fibroblast cells. The difference between formulations in terms of peptide delivery from the endosome to the cytoplasm and even to the nucleus was investigated as a function of time. Characterization studies showed that both formulations possess acceptable size, shape and encapsulation efficiency but cellular uptake studies showed the important benefit of the pH-sensitive formulation over the classical one, in spite of liposome PEGylation. Indeed, stealth pH-sensitive liposomes were able to deliver hydrophilic materials strongly to the cytoplasm. Most importantly, when encapsulated in pH-sensitive stealth liposomes, the peptide was able to reach the nucleus of tumorigenic and non tumorigenic breast cancer cells.

Liposomes and parameters affecting their skin penetration behaviour

It is known that classical and more recently deformable liposomes have shown their ability to increase dermal and transdermal drug delivery. However their penetration mechanism remains controversial and not understood at this time. Different vesicle compositions, preparation methods and drugs have been used, giving vesicles with diverse characteristics. This fact, in addition to the experimental conditions, probably accounts for the lack of understanding with regards to their mode of action. This review focuses on the penetration behaviour of liposomes as a function of their composition. Parameters influencing the mode of action of liposomes are discussed, such as the preparation method, lipid composition, entrapment efficiency, addition of an edge activator or ethanol, size and lamellarity. It also reviews parameters of the experimental set-up (usually Franz type diffusion cells are used for in vitro skin absorption studies) which could affect results of diffusion, such as the skin used, receptor fluid composition, occlusive or non occlusive mode and washing step. The purpose is to highlight parameters which are beneficial or detrimental to skin penetration with the goal of understanding the penetration mechanism of liposomes.

Efficacy and cost-effectiveness: A study of different treatment approaches in a tertiary pain centre

Chronic pain is considered to be a complex phenomenon, involving an interrelation of biological, psychosocial and sociocultural factors. Currently, no single treatment or therapy can address all aspects of this pathology. In our expert tertiary pain centre, we decide to assess the effectiveness of four treatments for chronic pain classically proposed in our daily clinical work: physiotherapy; psycho‐education; physiotherapy combined with psycho‐education; and self‐hypnosis/self‐care learning.

Do management and executive share the same perception on the critical issues facing the front-line nursing staff?

ABSTRACT Changes in managerial practices increasingly distance managers from staff by promoting rotation. It could be thought that this distance changes the perception managers have of work constraints and resources. This study attempts to tackle staff and leadership disparate views on the issues facing front-line nursing staff. We sent an online questionnaire on work constraints and good practices to nursing chiefs from Belgium hospitals and conducted focus groups with their ‘front-line’ nursing staff in order to compare perceptions. 40% of the chief nurses mentioned as a regular problems for their staff: production pressure, working time, doctors–nurses collaboration and managing new staff. Except for the ‘productive pressure’, these issues are rather considered by the staff as occasional problems. Front-line staffs evaluate infrastructure, heat, working positions as more common problems. However, statistical analyses showed one significant difference in perception: management of incidents/accidents. Health care organizations should promote participatory management tools both to diagnose work constraints and to elaborate action priorities in order to guarantee a shared understanding of decisions making between staff and supervisors.

Cognitive support for a better handoff: does it improve the quality of medical communication at shift change in an emergency department?

Aim To improve the communication during shift handover in an emergency department. Methods We observed the handover process and analysed the discourse between physicians at shift change first, and then we created two cognitive tools and tested their clinical impact on the field. We used different measures to evaluate this impact on the health care process including the frequency and type of information content communicated between physicians, duration of the handoff, physician self-evaluation of the quality of the handoff and a posthandover study of patient handling. Results Our results showed that the patient’s medical history, significant test results, recommendations (treatment plan) and patient follow-up were communicated to a greater extent when the tools are used. We also found that physicians spent more time at the bedside and less time consulting medical records using these tools. Conclusion The present study showed how in-depth observations and analyses of real work processes can be used to better support the quality of patient care.