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Background: Treatment for metabolic and morphologic alterations in HIV-related lipodystrophy include medical therapy, physical exercise, and surgical interventions., Method: We assessed the efficacy and safety of a comprehensive multidisciplinary approach for treating morphological and metabolic alterations of the lipodystrophy syndrome in consecutive patients attending the Metabolic Clinic (MC) of the University of Modena and Reggio Emilia who had at least 2 evaluations over a 48-week period. 245 patients were evaluated: 143 (62.4%) were men, 74 (36.1%) presented with lipoatrophy, 10 (4.9%) with fat accumulation, 93 (45%) with mixed forms, 24 (11.3%) had hypercholesterolemia (LDL >160 mg/dL), 87 (38%) had hypertriglyceridemia (TG >150 mg/dL), 13 (5.7%) had diabetes (glucose >126 mg/dL), and 78 (44%) had insulin resistance (HOMA-IR >4)., Results: At follow-up, a significant improvement was observed in both objective and subjective variables. Anthropometric improvement was observed in waist to hip ratio, waist circumference, and right and left cheek dermal thickness measurements. A nonsignificant improvement was observed in fat and lean regional mass by DEXA; CT showed improvement in visceral and subcutaneous adipose tissue. Glucose, HOMA-IR, total cholesterol, and APO B improved. Subjective variables improved in aesthetic satisfaction., Conclusion: We conclude that the medical and surgical interventions proposed in this multidisciplinary therapeutic approach are efficacious and safe in the management of lipodystrophy.

Cellular localization of nanoparticles (Np) represents an important target in the understanding of their distribution after endovenous injection. The need of suitable devices and methodologies capable to detect Np in tissues or in cellular districts can be satisfied by Np which have to be easily recognizable by simple methods. Conjugations of poly(D,L-lactide-co-glycolide) with fluorescein and biotin allow fluorescent and immuno-histochemically active Np to be obtained. The fluorescein Np are detectable using fluorescent microscopy whereas biotin Np can be detected by optical microscopy after streptavidin-biotin-peroxidase complexation. In vivo experiments confirm the ability of these particles to be easily detected in the brain parenchyma or in the liver cell population according to the infusion pathway.

Liposomes loaded with ketorolac tromethamine salt were prepared by using a thin layer evaporation method. The physical properties of liposomes were studied by using atomic force microscopy (AFM) and transmission electron microscopy (TEM). The relationship between lipid composition, encapsulation efficiency, vesicle size, and the release of ketorolac tromethamine-loaded liposomes was studied. The drug content was found to be dependent on the lipidic composition used in the preparations and, in particular, vesicles containing both cationic lipids (dimethyldioctadecylammonium bromide and N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride), and phosphatidylcholine had a higher entrapped efficiency than liposomes with phosphatidylcholine alone or in the presence of cholesterol. Finally, the cationic liposomes appear to be useful as carriers for ketorolac tromethamine to control its in vitro release.

We report a preliminary study evaluating the encapsulation modalities in microparticles of the antiischemic drug N(6)-cyclopentyladenosine (CPA). The effects of release systems have been evaluated on the stability in human whole blood of CPA and its affinity toward human adenosine A(1) receptors. The microspheres were prepared by an emulsion-solvent evaporation method (different CPA amounts and two stirring rates were employed) using poly(lactic acid). Free and encapsulated CPA was incubated in human blood and the drug stability was analyzed. The affinity of CPA to human A(1) receptor was also obtained in the presence and in the absence of unloaded microspheres. The microspheres obtained using 1200 rpm showed a broad size distribution and a mean diameter value of 21+/-9 microm. Using 1700 rpm the mean diameter decreased to 5+/-2 microm and a more homogeneous size distribution was obtained. The CPA release changed with the particle size and the different amounts of drug employed during the preparation of the microspheres. The degradation in human whole blood of CPA encapsulated in the microspheres was negligible, with respect to that of free CPA. Affinity values of CPA obtained in the absence and in the presence of unloaded microspheres were the same.

Complexation of ursodeoxycholic acid (UDCA) with 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD) improves the water solubility and the dissolution rate of UDCA and may therefore increase its bioavailability. We compared the amount and the rate of biliary excretion of UDCA and biliary lipid secretion after a single oral administration of UDCA in 3 different pharmaceutical formulations [UDCA-HPbetaCD ('urso-beta-cyclodextrin'), UDCA suspension and UDCA capsule] at 3 different dosages each, in 11 groups (2 control groups) of bile fistula rats. UDCA excretion increased with an increase in dose, biliary UDCA recovery and peak secretion were significantly higher after administration of UDCA-HPbetaCD than after UDCA in suspension or capsule. This enhancement of biliary excretion may achieve greater UDCA enrichment in the bile acid pool than conventional pharmaceutical UDCA formulations, this giving to UDCA-HPbetaCD a considerable therapeutical potential., (Copyright 2001 S. Karger AG, Basel.)

Cyclodextrins improve the water-solubility of drugs and can mask their haemolytic effect in parenteral use. Because the mechanism by which bile acids induce haemolysis is poorly understood, it has been investigated in the presence of 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD). The haemolytic effect of 1.8 mM solutions of cholic acid, chenodeoxycholic acid (CDCA), deoxycholic acid and ursodeoxycholic acid (UDCA) in isotonic buffer at pH 7.4 was investigated at 37 degrees C in the presence of HP-beta-CyD at concentrations from 0.18 to 32 mM. No haemolytic effect was evident for cholic acid and UDCA. The haemolytic effect of the other bile acids was reduced by addition of HP-beta-CyD and was prevented at a molar ratio of 1:1 owing to complex formation. An HP-beta-CyD:bile acid molar ratio greater than 5:1 had a different effect on the erythrocyte membrane, irrespective of the identity of the bile acid; the effect was in accordance with the complexion affinities. In the absence of HP-beta-CyD, the haemolytic effect of CDCA and deoxycholic acid appeared related to their capacity to form a surface monolayer and to solubilize the components of the erythrocyte membrane. The haemolytic effect observed after complexation of the bile acids appeared to be solely the effect of HP-beta-CyD, which was able to form a reversible inclusion complex with lipophilic components of the erythrocyte membranes at concentrations higher than 12 mM.

Tablets containing the inclusion complex of ursodeoxycholic acid (UDCA) with 2-hydroxypropyl-beta-cyclodextrin were prepared by direct compression. Plasma concentrations of UDCA were determined in six healthy volunteers after oral administration of tablets containing the inclusion complex or UDCA alone (Ursacol). Following the administration of the complex tablets, the mean area under the plasma concentration curve (AUC) and the maximum UDCA plasma concentration (Cmax) were significantly higher than those obtained after the administration of the commercial ones. Moreover, the time of maximum plasma concentration (tmax) appeared at a shorter time. These results may be explained by the increase of the UDCA dissolution rate via complex formation.

The effect of drug loading level both on dynamic swelling and drug release was evaluated using crosslinked gelatin microspheres. Owing to water penetration the microsphere diameter went first to a maximum value, which was not affected by the payload; the diameter gradually approached to an equilibrium swollen value, which was affected by drug loading level. Water absorption increases and drug diffusion decreases the microsphere diameter. Obviously, the diameter variation depends on the factor (water absorption or drug diffusion) predominating in the process. As the payload affected only the equilibrium swollen value it is reasonable to hypothesize that drug loading level has a greater effect on drug diffusion than on polymer relaxation. This rationale could explain the increase of the diffusion component of the drug release process as the payload increased.

The cross-linking time period affected both the swelling and release processes of cross-linked gelatin microspheres. In the dynamic swelling procedure, the combination of both phenomena of microparticle swelling and drug diffusion produced at first the increase and then the decrease of the diameter of a loaded microsphere. The increase of the cross-linking time period produced the shift of the penetrant transport from anomalous to super-case II kinetics. This behaviour could justify the decrease of the diffusion component of the drug release as the cross-linking time period increased.

The effect of the concentration of a cross-linking agent (gelatin hardener) on gelatin microspheres was evaluated. A concentration increase of the gelatin hardener (formaldehyde) produced a decrease of drug loading, swelling degree and drug release rate. The cross-linking agent concentration affected also the kinetics of water absorption and drug release. This paper suggests a decreasing significance of the diffusion-type mechanism of drug release as the concentration of the cross-linking agent increased.

Ethylene:vinyl acetate pellets were loaded at 20 degrees C by swelling the polymer with 1 and 3% (w/v) chloroformic solutions of tolbutamide. The energy dispersive X-ray analysis showed different concentrations of the tolbutamide sulfur in the pellets sections according to the loading time. At the beginning of the loading process, the sulfur in the pellets showed two concentration peaks which later joined in the center of the section before reaching a homogeneous distribution. The concentration peaks might depend on a drug sieving process as the solution flow reaches a less swollen inner area. Therefore, the concentration distribution of the drug would be affected by the size of the polymer network, which is related to the volume of the solvent in the polymer. Another possible explanation of these concentration profiles is that they could be a result of the solvent evaporation process. The concentration distribution of the drug becomes homogeneous only after the complete swelling of all of the polymer.