[An importance of colloid chemical characterization of liposomes for DDS in a large scale production].

Efficacy and safety data of liposomal drugs in a laboratory environment are often not reproduced on an industrial production scale. This is largely due to the fact that the colloid-chemical properties of the liposomes manufactured on a small scale are not reproduced in large scale production. Though the size and the electric charge of liposomes are measured and are adequately specified in relation to the bio-distributions in most developments of liposomes (1), uniformity of lipid components, exposure of bio-chemically important functional groups on the outer surface of liposomes (2), fixed aqueous layer thickness (FALT), number of the lipid bilayers, etc., are dependent upon the scale of production. Nevertheless these properties are not always exactly specified. Uniformity, especially of the functional groups on the membrane surface can be assessed chemically or bio-chemically with fractionated samples, and FALT can be easily determined through electro-chemical means (3). In this review, colloid chemical characterization of liposomes is introduced, FALT as an example, and its importance in a quality control of a liposomal product in an industrial scale production is shown. Methoxy-polyethyleneglycol-diacylglycerol (PEG-DAG) with varying PEG chain length and acyl chains were synthesized, FALT of liposomes coated with PEG-DAG determined and tissue distribution in tumor bearing mice. The higher incorporation ratio of PEG-DAG into liposomal membrane was observed with PEG-DAG with short acyl chains (myristoyl) and a small PEG molecular weight (1000). The easier to incorporate, the easier to be stripped in the serum. The disposition data in the rats well reflected the colloid chemical and in vitro data of the PEG liposomes. Galactosyl-carbonyl-propionyl-polyethyleneglycol-diacylglycerol (Gal-PEG-DAG) with oxyethylene number, n = 10, 20 and 40 were synthesized. The exposure of the galactose residue beyond the fixed aqueous layer of liposomes coated with Gal-PEG-DAG was monitored by a lectin, Ricinus communis agglutinin (RCA) induced agglutination, the half life in the blood after i.v. injection into rats, organ distribution determined and intrahepatic distribution studied. Only the liposomes containing the Gal-PEG10-DAG aggregated with the lectin, indicating that only with this derivative the galactose group was adequately exposed. The Gal-PEG10-DAG liposomes were cleared from the plasma with a half life of 0.3 h. The plasma elimination could be attributed entirely to increased uptake by the liver. The increased liver uptake was almost entirely attributed to increased uptake by the non-parenchymal cell. Incorporation of PEG-DSPE in to the Gal-PEG10-DAG liposomes caused 1) a three-fold increase in blood circulation time, 2) a small but significant decrease in hepatic uptake after 20 h and 3) a significant shift in intrahepatic distribution in favor of the hepatocytes, comparable to that of the control liposomes. In conclusion, therapeutic efficacy and safety of liposomes can be controlled by their colloid chemical, more exactly, surface chemical properties. By setting up reasonable quality control specification of the properties in laboratory and examining the specifications satisfied in upscaling, the efficacy and safety are reproduced in a large scale product.

Interstitial lung disease in rheumatoid arthritis: assessment with high-resolution computed tomography.

Interstitial lung disease (ILD) is a frequent manifestation of rheumatoid arthritis (RA), and it has a close bearing on the prognosis of RA patients. Computed tomography (CT) has been shown to be excellent for the diagnosis of diffuse lung disease. In this study chest radiographs and high-resolution CT (HRCT) scans were obtained in 91 patients with RA to evaluate their ILD precisely. By HRCT 43 patients could be diagnosed as having interstitial pneumonitis (IP), and 5 could be diagnosed as having bronchiolitis. The remaining 43 patients were normal by HRCT. Chest radiographic findings were consistent with the HRCT findings in approximately 50% of patients with IP. HRCT was superior to chest radiographs for the detection of early interstitial changes. The histogram of HRCT values might be a useful adjunct to HRCT diagnosis by adding some degree of objectivity. HRCT is useful for the diagnosis of ILD in patients with RA.

[MR imaging in the assessment of lung cancer patients: primary lung cancer staging, evaluation of therapeutic effect and diagnosis of recurrent tumor].

Magnetic resonance imaging and computed tomography were compared in a prospective study of 137 lung cancer patients proved by surgery or autopsy for determining the staging, evaluation of therapeutic effect and diagnosis of recurrent tumor. 1. Lung cancer staging In peripheral lung cancer, T1 and T2 relaxation times of the tumors before operation have some correlation with those of operated specimens. These relaxation times, however, are of limited nodule characterization. Hilar mass and adjacent pulmonary consolidation (obstructive pneumonia or collapse) can be distinguished on T2-weighted image (77%) and Gd-DTPA enhanced image (80%). Therefore these images help in distinguishing tumor from peripheral lung disease. In the diagnosis of tumor invasion to the heart and great vessels, MRI is superior to CT because MRI can be helpful in distinguishing true mass from heart and great vessels. As for the chest wall, MRI is more useful than CT in detecting tumor invasion especially to the thoracic inlet and superior regions. In the diagnosis of mediastinal and hilar lymphadenopathy, MRI is equivalent or slightly inferior to CT, but MRI can easily demonstrate the lymphadenopathy at subcarinal region on coronal image. 2. Evaluation of therapeutic effect in lung cancer patients treated by radiation and chemotherapy MRI patterns of therapeutic effect was divided into 3 types. It is suggested that there is some correlation between these patterns and histologic types. MRI can easily demonstrate necrotic area on T2-weighted and Gd-DTPA enhanced images. 3. Diagnosis of recurrent tumor in treated lung cancer Concerning detecting recurrent tumor after surgery or irradiation, and delineating tumor from radiation pneumonitis, T2-weighted and Gd-DTPA enhanced images are of clinical value.