The Shape/Morphology Balance: A Study of Stealth Liposomes via Fractal Analysis and Drug Encapsulation

Purpose

Fractal analysis was used as a tool in order to study the morphological characteristics of PEGylated liposomes. We report on the morphological characteristics of stealth liposomes composed of DPPC and DPPE-PEG 3000 in two dispersion media using fractal analysis.

Methods

Light scattering techniques were used in order to elucidate the size, the morphology and the surface charge of PEGylated liposomes as a function of PEGylated lipid concentration and temperature. Fluorescence spectroscopy studies revealed a microenvironment of low polarity inside the liposomal membranes.

Results

All formulations were found to retain their physicochemical characteristics for at least 3 weeks. The hydrodynamic radii (R_h) of stealth liposomes were stable in the process of heating up to 50°C; while the fractal dimension values (d_f) which correspond to their morphology, have been changed during heating. Hence, these results are a first indication of the presence of a heterogeneous microdomain structure of the stealth liposomal system. The amphiphilic drug indomethacin (IND) was successfully encapsulated within the liposomes and led to an increased size of stealth liposomes, while the morphology of liposomal vectors changed significantly at the highest molar ratio of PEGylated lipid.

Conclusions

We can state that this approach can promote a new analytical concept based on the morphological characteristics and quantify the shape of drug carriers complementary to that of the conventional analytical techniques.     

Application of the Monte Carlo method for the calibration of an in situ gamma spectrometer

A MCNP model was developed for the efficiency calibration of an in situ gamma ray spectrometry system based on a high purity germanium (HPGe) detector. The detector active crystal volume was adjusted semi-empirically against experimental measurements. Calculated full energy peak efficiency curves, over the photon energy range between 50 keV and 5 MeV, are presented for surface and slab source configurations. The effect of different collimator apertures and the contribution of different HPGe crystal regions in the detector response are also shown.     

Impact of source data verification on data quality in clinical trials: an empirical post hoc analysis of three phase 3 randomized clinical trials

AIM

The aim of this project was to perform an empirical evaluation of the impact of on site source data verification (SDV) on the data quality in a clinical trial database to guide an informed decision on selection of the monitoring approach.

METHODS

We used data from three randomized phase III trials monitored with a combination of complete SDV or partial SDV. After database lock, individual subject data were extracted from the clinical database and subjected to post hoc complete SDV. Error rates were calculated with focus on the degree of on study monitoring and relevance and analyzed for potential impact on end points.

RESULTS

Data from a total of 2566 subjects including more than 3 million data fields were 100% source data verified post hoc. An overall error rate of 0.45% was found. No sites had 0% errors. 100% SDV yielded an error rate of 0.27% as compared with partial SDV having an error rate of 0.53% (P < 0.0001). Comparing partly and fully monitored subjects, minor differences were identified between variables of major importance to efficacy or safety.

CONCLUSIONS

The findings challenge the notion that a 0% error rate is obtainable with on site monitoring. Data indicate consistently low error rates across the three trials analyzed. The use of complete vs. partial SDV offers a marginal absolute error rate reduction of 0.26%, i.e. a need to perform complete SDV of about 370 data points to avoid one unspecified error and does not support complete SDV as a means of providing meaningful improvements in data accuracy.     

A comparison of arteriovenous fistulas and central venous lines for long-term chronic haemodialysis

Background

Despite the Fistula First initiative there is still reluctance to use arteriovenous fistulas (AVF) for chronic haemodialysis (HD) in children. Our aim was to compare outcomes of AVFs and central venous lines (CVL) in children on chronic HD in a centre where AVF is the primary choice for vascular access.

Patients and methods

This was a retrospective case notes analysis of access complications, dialysis adequacy and laboratory outcomes in children who underwent dialysis for at least a year by AVF (n?=?20, median age 14.2 years, range (2.9–16.5) and CVL (n?=?5, median age 2.4 years, range 2.0–12.2) between January 2007 and December 2010.

Results

Primary access failure rate (patient-months) was 1 per 78.8 for AVF (n?=?5) and 1 per 15.5 for CVLs (n?=?7, p?=?0.3). Failure thereafter was 1 per 131.3 and 1 per 18.5 for AVF and CVLs respectively (n?=?3 and 6 respectively; p?=?0.2). The annualised hospitalisation rate for access malfunction was 0.44% and 3.1% for AVFs and CVLs respectively (p?=?0.004). Patients with AVFs had a lower infection rate of 0.25 per 100 patient-months compared with CVL at 3.2 per 100 (p?=?0.002). There was no difference in dialysis adequacy or laboratory values between AVF and CVL groups. Access survival rates (including both primary and secondary access failure) were significantly higher for AVF compared with CVL (p?=?0.0002, hazard ratio?=?0.15, 95% confidence interval 0.04–0.37).

Conclusions

Patients with AVF spend less time in hospital than those dialysed by CVLs and have a much lower access infection rate. These findings emphasise the need to use AVF as first-line access for paediatric patients on chronic HD.