The Effect of Polymerization Method in Stereo-active Block Copolymers on the Stability of Polymeric Micelles and their Drug Release Profile

Purpose

To investigate the effect of polymerization method on the stability and drug release properties of polymeric micelles formed using stereo-active block copolymers.

Methods

Diblock copolymers consisting of methoxy poly ethylene oxide (MePEO) and poly(lactide)s (PLA)s of different stereochemistry were synthesized by bulk or solution polymerization. Polymers and micelles were characterized for their chemical structure by ¹H NMR, optical rotation by polarimetry, critical micellar concentration by fluorescence spectroscopy, thermal properties by differential scanning calorimetry, morphology by transmission electron microscopy and size as well as kinetic stability by dynamic light scattering. Release of encapsulated nimodipine from polymeric micelles at different levels of loading was also investigated.

Results

Solution polymerization yielded a higher degree of crystallinity for stereo-regular PLA blocks. Consequently, the related polymeric micelles were kinetically more stable than those prepared by bulk polymerization. At high drug loading levels, the release of nimodipine was more rapid from polymeric micelles with crystalline cores. At lower levels of drug loading, drug release was slower and independent of the stereochemistry of the core.

Conclusions

The results underline the effect of polymerization method in defining core crystallinity in stereoregular block copolymer micelles. It also shows the impact of core crystallinity on enhancing micellar stability and drug release.     

Pleuraerkrankungen

Zeitschrift für Pneumologie - Pleuraerkrankungen bieten ein weites Spektrum an Differenzialdiagnosen. Häufigstes Symptom ist der Pleuraerguss, der zur Luftnot führen kann. Neben der...     

Helicobacter pylori infection in Kazakhstan: effect of water source and household hygiene

The epidemiology of Helicobacter pylori infection and risk factors associated with its transmission are not well understood. Kazakhstan is country with two ethnic groups, Asian (Kazakhs) and Western (Russians), living under similar socioeconomic conditions. The aim of this study was to examine the seroepidemiologic pattern of H. pylori and hepatitis A among the same individuals from both ethnic groups, with emphasis on water source and household sanitation practices. This was a cross-sectional seroepidemiologic study conducted among unrelated healthy individuals in Kazakhstan. From May through August 1999, individuals between the ages of 10 and 60 years from Almaty, Kazakhstan, were invited to participate. Demographic information, socioeconomic factors, living conditions, and various aspects of the local household environment including access to water were collected. A clean water index (CWI) was created based on combined factors, consistency of boiling water before drinking, frequency of storing and reusing water, and frequency of bathing and showering. H. pylori and hepatitis A antibodies were assessed by enzyme-linked immunosorbent assay. Two hundred eighty-eight individuals between the ages of 10 and 60 years participated. The prevalence of H. pylori infection was almost identical among the two ethnic groups (Russians 79% and Kazakhs 80%). H. pylori infection was inversely correlated with the CWI (i.e., 56%, 79%, and 95% for high, middle, and low, respectively (P < .05). Drinking river water had highest risk of H. pylori infection (OR = 13.6, 95% CI = 1.8-102.4; P < .01, compared with tap water). Crowding showed no significant effect on H. pylori prevalence. Anti-HAV antibodies were found in 86% of the population, 90% among the Russians versus 82% among the Kazakhs (OR = 1.8, 95% CI = 1.1-3.8, P = .05). Although the two infections were highly correlated (P < .001), antibody to both infections were present simultaneously in only 74%. The prevalence of H. pylori infection in Kazakhstan is very high. The data suggest that transmission of H. pylori can be water borne, related to poor sanitary practices, or both. The high prevalence of antibodies to H. pylori and HAV among this population is a marker for poor sanitation and hygienic practices. Reducing the rate of H. pylori transmission will require improvements in overall sanitation including clean water, waste disposal, as well as in household hygienic practices.     

Circulating anti-HLA antibodies in patients with chronic hepatitis C: relation to disease activity

The human leukocyte antigens (HLA) may influence host immune to infection. In the mean time chronic hepatitis C (CHC) results in the appearance of a variety of autoantibodies. We investigated the frequency of circulating anti-HLA antibodies and none organ specific autoantibodies in patients with chronic hepatitis C at different stages of disease activity. Sixty-seven untreated male patients with CHC (anti-HCV antibody and HCV RNA positive), in whom 38 had elevated serum alanine aminotransferase (ALT) levels and 29 persistently normal serum ALT values, and 23 age-matched normal male subjects were studied. None of them had a history of blood transfusion. Sera were analyzed for immunoglobulin G-anti-HLA class I and class II antibodies by enzyme-linked immunosorbant assay, and for non-organ-specific autoantibodies (antinuclear, anti-smooth muscle, anti-mitochondrial and anti-liver/kidney microsomes type 1 antibodies) using indirect immunofluorescence technique. Circulating anti-HLA class I and class II antibodies were detected in 15/67 (22.4 %) and 11/67 (16.4 %) respectively, while none of normal controls had detectable anti-HLA antibodies in the serum. The frequency of detecting anti-HLA antibodies was significantly higher in patients with elevated serum ALT than persistently normal serum ALT values (31.6 % vs 10.3 %; P = 0.039) and was associated with non-organ-specific serum autoantibodies in 11/15 (73.3 %) patients. Those with circulating anti-HLA antibodies had significantly higher levels of serum aminotransferases, gamma-glutamyl transpeptidase, viral load and necroinflammatory and fibrosis scores in liver biopsies than patients with negative anti-HLA antibody (P < 0.001). In conclusions, the presence of circulating antibodies against HLA class I and class II molecules in HCV antibodies may represent an autoimmune response to HLA antigens and may play a pathogenetic role in the induction of the HCV-related chronic liver disease.     

Radiation Exposure from Diagnostic Imaging Studies Among Patients with Inflammatory Bowel Disease in a Safety-Net Health-Care System

Background/Aims

Radiographic imaging studies are important in the management of patients with inflammatory bowel disease (IBD), but are associated with radiation exposure. IBD patients in a safety-net health-care system may be at risk of high exposure to radiation. Our purpose was to identify associations of high-dose radiation exposure among an ethnically diverse cohort of IBD patients in a safety-net health-care system.

Methods

A study was performed on patients with IBD receiving care from the Harris County Hospital District. Radiation exposure was calculated using total number of imaging studies performed between from 2000 and 2010 and estimates of radiation dose per study. Associations of high-dose radiation exposure, defined as a cumulative effective dose (CED) >50 mSv, were identified by using univariate and multivariate logistic regression.

Results

The study cohort of 278 patients with IBD was ethnically diverse, with 30 % Caucasian, 44 % African–American, and 26 % Hispanic. The median CED was 10.40 mSv (SD 20.02). Annualized radiation doses were 3.45 mSv/year among patients with Crohn’s disease (CD) and 1.27 mSv/year among patients with ulcerative colitis, p < 0.02. Approximately 13 % of IBD patients received a CED >50 mSv. There were no differences in radiation exposure based on age, gender, or race/ethnicity.

Conclusions

A small proportion of IBD patients in a safety-net health-care system received high doses of diagnostic radiation exposure. Use of diagnostic imaging studies that limit radiation exposure should be encouraged.     

Validation of family history of breast cancer and identification of the BRCA1 and other syndromes using a population-based cancer registry

A major risk factor for breast cancer is family history of the disease in first-degree relatives. This study evaluates the validity of family history information on breast cancer in mothers and sisters of breast cancer probands from the cancer registry (CR) compared to personal interviews (PI) of 359 consecutive population-based cases of breast cancer. Breast cancer is seen in mothers of 14% of probands by CR compared to 12% by PI. Further, 13% of probands have a sister with breast cancer using CR compared to 12% by PI. Using PI as the standard, the sensitivity of the CR family history data in mothers is 92% and the specificity is 99%, while in sisters they are 88% and 99%, respectively. These estimates were calculated on cases where family history information is available in the CR. Sensitivity and specificity are recalculated, recording an “error” whenever family history information is not available, and they are 75% and 68%, respectively, for mothers and 72% and 70%, respectively, for sisters. Estimates of proband-mother and proband-sisters familial breast cancer from CR and PI are sufficiently similar to warrant the use of CR family history data in studies of genetic epidemiology. The family phenotype consistent with the BRCA1 syndrome was found in four (1.1%) probands, all below age 50 years, while for BRCA2 there were five (1.4%) probands, three below age 50 years and two 50 years or older. Site-specific familial breast cancer was found in 23 (6.4%) probands. Population-based multiple-case breast cancer families can rapidly be identified through CR. These families can make substantial contributions to the study of genetic and environmental etiology of the disease as well as benefit from preventive and therapeutic efforts. As new knowledge and tools in molecular genetics become available, there is an urgent need for large population-based registries of families at high risk for cancer. © 1996 Wiley-Liss, Inc.