100 research outputs found
Assessment of drug entrapment within liposomes using photophysical probes
The photophysical and photochemical behavior of (R)-cinacalcet (CIN) and (S)-naproxen (NPX) entrapped within liposomes has been studied. For this purpose, liposome encapsulated drugs have been prepared through thin layer evaporation and characterized by transmission electron microscopy, cryoscopy scanning electron microscopy and dynamic light scattering. Steady state and time-resolved fluorescence experiments showed similar spectra, emission quantum yields, singlet energies and lifetimes for the selected drugs, outside and inside liposomes. By contrast, laser flash photolysis experiments revealed an important enhancement of the triplet lifetimes for entrapped drugs inside liposomes, indicating the spatial confinement existing in the microenvironment prevailing in these biomimetic entities. Thus, this photophysical property shows potential as a non-invasive, direct and valuable tool to monitor encapsulation of photoactive drugs and to probe the intraliposome environment. In addition, it provides a new quantitative indicator of the capability of liposomes to act as drug carriers.We gratefully acknowledge financial support from the Carlos III Institute of Health (Servet Contract CP11/00154 for I.A. and Red RETICS de investigacion de Reacciones Adversas a Alergenos y Farmacos, RIRAAF) and from Ministero dell'Istruzione, dell'Universita e della Ricerca (M.I.U.R. Italy).Oliverio, F.; Nuin PlĂĄ, NE.; Andreu Ros, MI.; Ragno, G.; Miranda Alonso, MĂ. (2014). Assessment of drug entrapment within liposomes using photophysical probes. European Journal of Pharmaceutics and Biopharmaceutics. 88(2):551-555. https://doi.org/10.1016/j.ejpb.2014.06.013S55155588
A consensus review on the development of palliative care for patients with chronic and progressive neurological disease
BACKGROUND AND PURPOSE:
The European Association of Palliative Care Taskforce, in collaboration with the Scientific Panel on Palliative Care in Neurology of the European Federation of Neurological Societies (now the European Academy of Neurology), aimed to undertake a review of the literature to establish an evidence-based consensus for palliative and end of life care for patients with progressive neurological disease, and their families.
METHODS:
A search of the literature yielded 942 articles on this area. These were reviewed by two investigators to determine the main areas and the subsections. A draft list of papers supporting the evidence for each area was circulated to the other authors in an iterative process leading to the agreed recommendations.
RESULTS:
Overall there is limited evidence to support the recommendations but there is increasing evidence that palliative care and a multidisciplinary approach to care do lead to improved symptoms (Level B) and quality of life of patients and their families (Level C). The main areas in which consensus was found and recommendations could be made are in the early integration of palliative care (Level C), involvement of the wider multidisciplinary team (Level B), communication with patients and families including advance care planning (Level C), symptom management (Level B), end of life care (Level C), carer support and training (Level C), and education for all professionals involved in the care of these patients and families (Good Practice Point).
CONCLUSIONS:
The care of patients with progressive neurological disease and their families continues to improve and develop. There is a pressing need for increased collaboration between neurology and palliative care
Challenges and Pitfalls in the Management of Parathyroid Carcinoma: 17-Year Follow-Up of a Case and Review of the Literature
A 29-year-old man presented to his primary care physician with nausea, severe weight loss and muscle weakness. He had a hard, fixed neck swelling. He was severely hypercalcaemic with 10-fold increased parathyroid hormone (PTH) concentrations. A diagnosis of primary hyperparathyroidism was established and the patient was referred for parathyroidectomy. At neck exploration, an enlarged parathyroid gland with invasive growth into the thyroid gland was found and removed, lymph nodes were cleared and hemithyroidectomy was performed. A suspected diagnosis of parathyroid carcinoma was confirmed histologically. Serum calcium and PTH levels normalised post-operatively, but hyperparathyroidism recurred within 3Â years of surgery. Over the following 17Â years, control of hypercalcaemia represented the most difficult challenge despite variable success achieved with repeated surgical interventions, embolisations, radiofrequency ablation of metastases and treatment with calcimimetics, bisphosphonates and haemodialysis using low-dialysate calcium. In this paper, we report the challenges and pitfalls we encountered in the management of our patient over nearly two decades of follow-up and review recent literature on the topic
Photoactive assemblies of organic compounds and biomolecules: drug-protein supramolecular systems
[EN] The properties of singlet and triplet excited states are strongly medium-dependent.
Hence, these species constitute valuable tools as reporters to probe compartmentalised
microenvironments, including drug@protein supramolecular systems. In the present
review, the attention is focused on the photophysical properties of the probe drugs
(rather than those of the protein chromophores) using transport proteins (serum
albumins and 1-acid glycoproteins) as hosts. Specifically, fluorescence measurements
allow investigating the structural and dynamic properties of biomolecules or their
complexes. Thus, the emission quantum yields and the decay kinetics of the drug singlet
excited states provide key information to determine important parameters such as the
stoichiometry of the complex, the binding constant, the relative degrees of occupancy of
the different compartments, etc. Application of the FRET concept allows determining
donor-acceptor interchromophoric distances. In addition, anisotropy measurements can
be related to the orientation of the drug within the binding sites, where the degrees of
freedom for conformational relaxation are restricted. Transient absorption spectroscopy
is also a potentially powerful tool to investigate the binding of drugs to proteins, where
formation of encapsulated triplet excited states is favoured over other possible processes
leading to ionic species (i. e. radical ions), and their photophysical properties are
markedly sensitive to the microenvironment experienced within the protein binding
sites. Even under aerobic conditions, the triplet lifetimes of protein-complexed drugs are
remarkably long, which provides a broad dynamic range for identification of distinct
triplet populations or for chiral discrimination. Specific applications of the laser flash
photolysis technique include the determination of drug distribution among the bulk
solution and the protein binding sites, competition of two types of proteins to bind a
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drug, occurrence of drug-drug interactions within protein binding sites, enzymatic-like
activity of the protein or determination of enantiomeric compositions.
The use of proteins as supramolecular hosts modifies the photoreactivity of
encapsulated substrates by providing protection against oxygen or other external
reagents, by imposing conformational restrictions in the binding pockets, or by
influencing the stereochemical outcome. In this review, a selected group of examples is
presented including decarboxylation, dehalogenation, nucleophilic addition,
dimerisation, oxidation, Norrish type II reaction, photo-Fries rearrangement and 6
electrocyclisationFinancial support from the Spanish Government (CTQ2010-14882, JCI-2011-09926, RyC-2007-00476), from the EU (PCIG12-GA-2012-334257), from the Universitat PolitĂšnica de ValĂšncia (SP20120757) and from the ConsellerĂa de EducaciĂł, Cultura i Esport (PROMETEOII/2013/005, GV/2013/051) is gratefully acknowledged.VayĂĄ PĂ©rez, I.; Lhiaubet-Vallet, VL.; JimĂ©nez Molero, MC.; Miranda Alonso, MĂ. (2014). Photoactive assemblies of organic compounds and biomolecules: drug-protein supramolecular systems. Chemical Society Reviews. 43:4102-4122. https://doi.org/10.1039/C3CS60413FS410241224
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