The effect of thermosensitive liposomal formulations on loading and release of high molecular weight biomolecules.

Thermosensitive liposomes are clinically-relevant nanocarriers which have been used to deliver chemotherapeutic agents to tumors in combination with local hyperthermia. However, the encapsulation and release of macromolecular therapeutic agents (proteins, nucleic acids, bioactive polymers) is often hindered by their instability during the liposome formation as well as by the low encapsulation efficiency. The objective of this study was to investigate the influence of the thermosensitive liposomal formulation on the encapsulation and release of low and high molecular weight hydrophilic drugs, in order to identify the key parameters to control during nanocarrier design, depending on the specific drug delivery application. Thermosensitive liposomes with different formulations were prepared through the combinations of different lipids, including dipalmitoylphosphatidylcholine (DPPC), distearoylphosphatidylcholine (DSPC), cholesterol (Chol), 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphocholine (P-Lyso-PC), and the PEGylated lipid distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(PEG)-2000 (DSPE-PEG2000). The thin film hydration method was used for liposome preparation and loading of different water soluble molecules. The encapsulation efficiency and release profiles were investigated for a low molecular weight compound such as carboxyfluorescein (CF), proteins (albumin), and hydrophilic polymers which do not interact with the lipid bilayer, such as a linear dextran and a poly(ethylene glycol)-based star polymer. An optimised liposomal formulation [DPPC/P-lyso-PC/DSPE-PEG2000 90/10/4 (mol/mol) (LTSL)] was chosen for further application in encapsulating therapeutic proteins, such as lysozyme and the brain-derived neurotrophic factor (BDNF), which are recognized as drug carriers and potential therapeutic agents for kidney diseases and neurological disorders.

Ultrasmall polymeric nanocarriers for drug delivery to podocytes in kidney glomerulus.

We explored the use of new drug-loaded nanocarriers and their targeted delivery to the kidney glomerulus and in particular to podocytes, in order to overcome the failure of current therapeutic regimens in patients with proteinuric (i.e. abnormal amount of proteins in the urine) diseases. Podocytes are glomerular cells which are mainly responsible for glomerular filtration and are primarily or secondarily involved in chronic kidney diseases. Therefore, the possibility to utilise a podocyte-targeted drug delivery could represent a major breakthrough in kidney disease research, particularly in terms of dosage reduction and elimination of systemic side effects of current therapies. Four-arm star-shaped polymers, with/without a hydrophobic poly-ε-caprolactone core and a brush-like polyethylene glycol (PEG) hydrophilic shell, were synthesised by controlled/living polymerisation (ROP and ATRP) to allow the formation of stable ultrasmall colloidal nanomaterials of tuneable size (5-30nm), which are able to cross the glomerular filtration barrier (GFB). The effects of these nanomaterials on glomerular cells were evaluated in vitro. Nanomaterial accumulation and permeability in the kidney glomerulus were also assessed in mice under physiological and pathological conditions. Drug (dexamethasone) encapsulation was performed in order to test loading capacity, release kinetics, and podocyte repairing effects. The marked efficacy of these drug-loaded nanocarriers in repairing damaged podocytes may pave the way for developing a cell-targeted administration of new and traditional drugs, increasing efficacy and limiting side effects.

[Geriatric telecare, a new model of assistance: a pilot study]. / Teleassistenza geriatrica continua. Nuovo modello di supporto all'anziano fragile: progetto pilota.

Aim of this pilot study was to evaluate the feasibility and explore the patients' acceptance of the -telecare model. The objective of this trial was to investigate the effects of a telecare system on elderly management at home. In a 24-months prospective study we enrolled all patients aged >65 years at risk of disability. During the two years of observation, each patient contact the TELECARE system. Telephone contact was followed by specific intervention and administration of a questionnaire evaluation. Over the 24 months we recorded 90,000 calls and 13,000 elderly were included in the telecare project. We analyzed the calls and the measures adopted. Our findings provide evidence of improved quality of life through clinical management at home from a telecare system. The use of this system had high adherence and was feasible for elderly patients and their family.

Improved assessment of left ventricular volumes and ejection fraction by contrast enhanced harmonic color Doppler echocardiography.

AIMS: Test the accuracy of contrast enhanced harmonic color Doppler technique (CHCD) to determine left ventricular volumes and ejection fraction (LVEF) compared to equilibrium radionuclide ventriculography (MUGA). METHODS AND RESULTS: A total of 35 patients were enrolled (male 74.3%) with the mean age of 64.5 +/- 10 years and 6.8 +/- 4.9 days between echo and MUGA scans. The correlation of LVEF by CHCD with MUGA was better (R2 = 0.89) than that of harmonic 2D (H2D) and of contrast enhanced harmonic 2D (CH2D) (R2 = 0.74, R2 = 0.82, respectively). The RMS residual of CHCD (0.056) was smaller than that of H2D and CH2D (0.079, 0.067, respectively). The LVED and LVES volumes by H2D, CH2D and CHCD correlate well with MUGA but there was a significant over estimation of LVED and LVES volumes by H2D and CH2D as compared to MUGA. Also, the RMS residuals were the lowest for the CHCD method. The CHCD had the highest mean inter-observer agreement (90.9%) for LVEF compared with H2D and CH2D (78.9% and 88.1%, respectively). CONCLUSIONS: CHCD has been feasible in all patients in the present study and it has shown a good concordance with ejection fraction and volumes provided by MUGA.