Paola Luciani

Paola Luciani
Universität Bern | UniBe · Department of Chemistry and Biochemistry

34.61
 · 
Professor

About

74
Publications
4,712
Reads
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1,291
Citations
Introduction
Liposome technology, sustained release, imaging, liver fibrosis, phospholipids
Research Experience
April 2019 - present
Universität Bern
Position
  • Full Professor of Pharmaceutical Technology
September 2015 - March 2019
Friedrich Schiller University Jena
Position
  • Professor (Associate, W2)
January 2012 - July 2015
ETH Zurich
Position
  • Group Leader
Education
October 2002 - February 2006
Sapienza University of Rome
Field of study
  • Chemical Sciences
October 1996 - July 2002
Sapienza University of Rome
Field of study
  • Chemistry

Publications

Publications (74)
Article
Full-text available
Phospholipids and their derivatives represent a broad range of multifunctional substances used as excipients or active ingredients by different industries due to their natural origin and unique properties. A fast and reliable quantification as well as comprehensive stability evaluation are of major importance in the process of development and quali...
Article
Full-text available
The remarkable number of new molecular entities approved per year as parenteral drugs, such as biologics and complex active pharmaceutical ingredients, calls for innovative and tunable drug delivery systems. Besides making these classes of drugs available in the body, injectable depot formulations offer the unique advantage in the parenteral world...
Article
Background: Extracellular vesicles (EVs) are a diverse group of membrane-bound nanovesicles potentially released by every cell. With the liver's unique ensemble of cells and its fundamental physiological tasks, elucidating the role of EV-mediated hepatic cellular crosstalk and their role in different pathologies has been gaining the attention of m...
Article
Full-text available
The pivotal role of hepatic stellate cells (HSCs) in orchestrating the bidirectional process of progression and regression of liver fibrosis makes them an ideal target for exploring new antifibrotic therapies. Essential phospholipids (EPLs), with their polyenylphosphatidylcholine (PPC) fraction, either alone or combined with other hepatoprotective...
Article
Full-text available
Vascularized composite allotransplantation (VCA), such as hand and face transplantation, is emerging as a potential solution in patients that suffered severe injuries. However, adverse effects of chronic high-dose immunosuppression regimens strongly limit the access to these procedures. In this study, we developed an in situ forming implant (ISFI)...
Article
In glioblastoma, the benefit from temozolomide chemotherapy is largely limited to a subgroup of patients (30–35%) with tumors exhibiting methylation of the promoter region of the O⁶-methylguanine-DNA methyltransferase (MGMT) gene. In order to allow more patients to benefit from this treatment, we explored magnetic resonance image-guided microbubble...
Article
Drugs that are neither lipophilic nor suitable for encapsulation via remote loading procedures are generally characterized by low entrapment efficiencies and poor retention in liposomes. One approach to circumvent this problem consists in covalently linking a lipid to the drug molecule in order to permit its insertion into the vesicle membrane. The...
Article
Hybrid self-assembling nanoparticles (hsaNPs) encapsulating bisphosphonates (BPs) recently showed very promising results in preclinic experiments for the treatment of brain tumor. However, the poor knowledge on the architecture of hybrid nanovectors is certainly one of the main reasons hampering further clinical and industrial development of these...
Article
Compared to conventional parenteral formulations injectable depot formulations, owing to a sustained drug release, offer several advantages, such as a reduced dosing frequency - and consequent improved compliance - or a predictable release profile. Additionally, fluctuations in the drug blood level may be smoothened and consequently side effects re...
Article
Several drugs have a short biological half-life and multiple administrations are needed to achieve a therapeutic effect. In addition, such drugs may not be suitable for oral administration because of degradation in the gastrointestinal tract and poor permeation through the gastrointestinal tract epithelium. Typical examples are high molecular weigh...
Article
Liposomal delivery is a well-established approach to increase the therapeutic index of drugs, mainly in the field of cancer chemotherapy. Here, we report the preparation and characterization of a new liposomal formulation of a derivative of lomeguatrib, a potent O6-methylguanine-DNA methyltransferase (MGMT) inactivator. The drug had been tested in...
Article
Ratiometric fluorescent probes offer an elegant option to detect analytes of interest and to normalize the signal of short-lived species such as reactive oxygen species (ROS) to a second fluorescence emission. The ratio of the two signals becomes thus independent of the sensor concentration and minimizes artefacts and intensity fluctuations. A summ...
Article
Compared to hemodialysis, peritoneal dialysis represents a more straightforward and less invasive alternative, though current solutions are not as effective. Herein, the feasibility of liposome-supported enzymatic peritoneal dialysis (LSEPD) is explored to increase the functionality of peritoneal dialysis for the model indication acute alcohol pois...
Article
The use of molecular markers for inflammation in the gastrointestinal tract could empower optical imaging modalities for early diagnosis and eventually personalized timely treatments. A major hurdle to the widespread use of functional fluorescence imaging is the absence of suitable contrast agents, in particular to be administered via the oral rout...
Article
Important elements for an efficient tumor targeted delivery are cancer-specific de novo- or over-expression of target receptors and their availability on the tumor cell surface. Peptides can be designed to selectively bind to such receptors and act as tumor-targeting ligands, as has been revealed in several preclinical studies. Notably, the amino a...
Article
Reactive oxygen species (ROS) are endogenously produced oxidants with various functions ranging from host defense to signaling. These transient species can cause severe damage to the body when their production is dysregulated or when environmental factors elevate their concentrations. To study their effects and prevent oxidative harm, tools capable...
Article
Aim: Our goal was to improve vincristine (VCR) based rhabdomyosarcoma (RMS) therapy by encapsulating the drug into liposomes. A targeting strategy was attempted to enhance tumor accumulation. Materials & methods: VCR was loaded in control and peptide-decorated liposomes via an active method. The interaction of an RMS-specific peptide with the pr...
Article
Extracellular detection of endogeneous analytes (e.g. superoxide) can provide important insights into mechanisms of homeostasis and diseases, such as tumorigenesis. A ratiometric probe with a fluorescent reference and an analyte-specific switch-on dye was developed. Detection of ROS in the extracellular milieu was ensured by connecting the two fluo...
Article
Full-text available
Techniques to image lymphatic vessel function in either animal models or in the clinic are limited. In particular, imaging methods that can provide robust outcome measures for collecting lymphatic vessel function are sorely needed. In this study, we aimed to develop a method to visualize and quantify collecting lymphatic vessel function in mice, an...
Article
Full-text available
Lymphatic vessels play important roles in the pathogenesis of many conditions that have an increased prevalence in the elderly population. However, the effects of the aging process on the lymphatic system are still rel- atively unknown. We have applied non-invasive imaging and whole-mount staining techniques to assess the lym- phatic vessel functio...
Article
Full-text available
Continuous focused ultrasound (FUS) has been mostly used to generate high temperatures necessary for tissue ablation. Pulsed FUS in combination with intravenously injected microbubbles has been shown to open the blood-brain barrier (BBB) to increase plasma-to-tissue permeability, thus presenting a new opportunity for local drug delivery to the targ...
Article
Full-text available
The role of lymphatic vessels is to transport fluid, soluble molecules, and immune cells to the draining lymph nodes. Here, we analyze how the aging process affects the functionality of the lymphatic collectors and the dynamics of lymph flow. Ultrastructural, biochemical, and proteomic analysis indicates a loss of matrix proteins, and smooth muscle...
Article
Full-text available
The role of lymphatic vessels is to transport fluid, soluble molecules, and immune cells to the draining lymph nodes. Here, we analyze how the aging process affects the functionality of the lymphatic collectors and the dynamics of lymph flow. Ultrastructural, biochemical, and proteomic analysis indicates a loss of matrix proteins, and smooth muscle...
Article
What if we could open the 2044 special issue of the Journal of Controlled Release? Which drug delivery technologies will have led the field? Which ones will have successfully reached the marketplace? In attempting to answer these questions, we selected a few recent technologies and concepts that could, in our opinion, play a crucial role in coming...
Article
Full-text available
Lymphatic vessels play an essential role in intestinal lipid uptake, and impairment of lymphatic vessel function leads to enhanced adipose tissue accumulation in patients with lymphedema and in genetic mouse models of lymphatic dysfunction. However, the effects of obesity on lymphatic function have been poorly studied. We investigated if and how ad...
Article
Full-text available
Methods to stabilize and retain enzyme activity in the gastrointestinal tract are investigated rarely because of the difficulty of protecting proteins from an environment that has evolved to promote their digestion. Preventing the degradation of enzymes under these conditions, however, is critical for the development of new protein-based oral thera...
Article
Over the last 15 years, discovery of key growth factors and specific molecular markers for lymphatic vessels has enabled a new era of molecular research on the lymphatic vascular system. As a result, it has been found that lymphangiogenesis, the expansion of existing lymphatic vessels, plays an important role in tumor progression and in the control...
Article
Over the last 15 years, discovery of key growth factors and specific molecular markers for lymphatic vessels has enabled a new era of molecular research on the lymphatic vascular system. As a result, it has been found that lymphangiogenesis, the expansion of existing lymphatic vessels, plays an important role in tumor progression and in the control...
Article
Knowledge about the mechanisms of regeneration of the lymphatic vasculature after surgical trauma is essential for the development of strategies for the prevention and therapy of lymphedema. However, little is known about the alterations of lymphatic flow directly after surgical trauma. We investigated lymphatic function in mice using near-infrared...
Article
Preclinical vascular research has been hindered by a lack of methods that can sensitively image and quantify vascular perfusion and leakage in vivo. In this study, we have developed dynamic near-infrared imaging methods to repeatedly visualize and quantify vascular leakage in mouse skin in vivo, and we have applied these methods to transgenic mice...
Article
A major problem in developing preventive and/or therapeutic treatment options for secondary lymphedema patients is the lack of reliable animal models to study the pathogenesis of lymphedema development. The aim of the current study was to investigate lymphatic flow in the leg and tail of healthy mice with Near-Infrared (NIR)-lmaging with regard to...
Article
Calcium channel blocker (CCB) overdose is potentially lethal. Verapamil and diltiazem are particularly prone to acute toxicity due to their dual effect on cardiac and vascular tissues. Unfortunately, conventional decontamination measures are ineffective in accelerating blood clearance and, to date, few efforts have been made to develop antidotes. T...
Article
The lymphatic vasculature provides a major route for tumor metastasis and inhibiting neolymphangiogenesis induced by tumors can reduce metastasis in animal models. Developmental biology studies have identified the transcription factor SOX18 as a critical switch for lymphangiogenesis in the mouse embryo. Here, we show that SOX18 is also critical for...
Article
Istaroxime, an investigational new drug that targets defective Ca(2+) cycling without compromising cardiac efficiency, may represent a promising and safe treatment of both acute and chronic heart failure. Even though the compound demonstrated good tolerability in a phase I/II safety study, symptoms related to the gastro-intestinal tract and pain at...
Article
Full-text available
Lymphatic vessels play a major role in cancer progression and in postsurgical lymphedema, and several new therapeutic approaches targeting lymphatics are currently being developed. Thus, there is a critical need for quantitative imaging methods to measure lymphatic flow. Indocyanine green (ICG) has been used for optical imaging of the lymphatic sys...
Article
Full-text available
Lipid-based drug carriers, such as liposomes or drug/lipid complexes, have been extensively investigated in a large number of therapeutic protocols such as gene therapy, drug delivery, drug targeting and antibacterial treatments, in preclinical and clinical trials. Many formulations composed of natural and/or synthetic amphiphiles have been studied...
Article
The inclusion of poly(ethylene glycol) monolaurate in liposomes formulated with dimyristoyl-sn-glycero-3-phosphocholine and certain cationic gemini surfactants improves their capability of condensing DNA into a psi phase and transfecting it into cells. Both the condensation, observed by circular dichroism, and the transfection efficiency are strong...
Article
Reported here is the thermotropic behavior of cationic gemini/phospholipid/DNA complexes investigated by synchrotron X-ray diffraction. At low temperature, DNA forms rectangular columnar superlattices between interdigitated bilayers. At temperatures above the lipid main phase transition, the transbilayer DNA ordering is partly preserved and DNA arr...
Article
Malignant gliomas represent the most common primary brain tumor: more than 50% of them are glioblastoma multiforme (GBM). Photodynamic therapy may offer a very good chance of targeted destruction of infiltrating GBM cells, thus increasing the survival time and recurrence-free interval of GBM patients. Among photosensitizing agents, meta-tetrahydrox...
Article
The impact of the length of gemini surfactant spacer on complexation and condensation of calf thymus DNA by cationic mixed phospholipid/gemini liposomes was investigated by monitoring the conformational changes of DNA by circular dichroism and the lipid hydration level by the emission characteristics of the fluorescent probe laurdan included in the...
Article
While much is known about the self-assembly of lipids on nanoscale, our understanding of their biologically relevant mesoscale organization remains incomplete. Here, we show for a cationic gemini lipid a sharp and reversible transition from small vesicles with an average diameter of approximately 40 nm to giant vesicles (GVs) with an average diamet...
Article
The properties of a novel disulfide-bond-containing gemini surfactant bis[N,N-dimethyl-N-hexadecyl-N-(2-mercaptoethyl)ammonium bromide] disulfide (DSP) were studied using a Langmuir balance, supported monolayers, differential scanning calorimetry, giant vesicles, and LUVs. In 150 mM NaCl the cmc for DSP was 7.5 microM whereas that of the monomer N,...
Article
The condensation of calf thymus DNA into the cholesteric-like psi-phase was observed by circular dichroism in liposome suspensions formulated with specific cationic gemini surfactants. The stereochemistry of the gemini spacer, the presence of specific functional groups, and the covalent link between the headgroups are fundamental issues in the cond...
Article
Cationic liposomes formulated with neutral 1,2-dimyristoyl-sn-glycero-3-phosphocholine and cationic gemini surfactants were used for transfecting different cell lines with a reporter gene. The efficiency in the transfection has been correlated to the high extent of DNA condensation observed by circular dichroism, condensation shown to depend heavil...
Article
Mixed cationic liposomes composed by different ratios of dimyristoyl-sn-glycero-phosphatidylcoline (DMPC) and a cationic gemini surfactant have been studied by various physicochemical tools as vehicles for m-tetrahydroxyphenylchlorin (m-THPC), a photosensitizer used in photodynamic therapy. Entrapment and location of m-THPC within the lipid double...
Article
Solid-supported multibilayers of the enantiomers of the cationic gemini surfactant 1, i.e., (2S,3S)-2,3-dimethoxy-1,4-bis(N-hexadecyl-N,N-dimethylammonium)butane dibromide (1a) and (2R,3R)-2,3-dimethoxy-1,4-bis(N-hexadecyl-N,N-dimethylammonium)butane dibromide (1b), have been studied by means of energy dispersive X-ray diffraction. The effect of su...

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Projects (2)
Project
Phospholipid-based therapeutics; biomarkers; extracellular vesicles