Andrew Ingham

A case-study investigating the physicochemical characteristics that dictate the function of a liposomal adjuvant.

A range of particulate delivery systems have been considered as vaccine adjuvants. Of these systems, liposomes offer a range of advantages including versatility and flexibility in design format and their ability to incorporate a range of immunomodulators and antigens. Here we briefly outline research, from within our laboratories, which focused on the systematic evaluation of cationic liposomes as vaccines adjuvants. Our aim was to identify physicochemical characteristics that correlate with vaccine efficacy, with particular consideration of the interlink between depot-forming action and immune responses. A variety of parameters were investigated and over a range of studies we have confirmed that cationic liposomes, based on dimethyldioctadecylammonium bromide and trehalose 6,6’-dibehenate formed a depot at the injection site, which stimulates recruitment of antigen presenting cells to the injection site and promotes strong humoral and cell-mediated immune responses. Physicochemical factors which promote a strong vaccine depot include the combination of a high cationic charge and electrostatic binding of the antigen to the liposome system and the use of lipids with high transition temperatures, which form rigid bilayer vesicles. Reduction in vesicle size of cationic vesicles did not promote enhanced drainage from the injection site. However, reducing the cationic nature through substitution of the cationic lipid for a neutral lipid, or by masking of the charge using PEGylation, resulted in a reduced depot formation and reduced Th1-type immune responses, while Th2-type responses were less influenced. These studies confirm that the physicochemical characteristics of particulate-based adjuvants play a key role in the modulation of immune responses.

Acute Effects of Vitamin D3 Supplementation on Muscle Strength in Judoka Athletes: A Randomized Placebo-Controlled, Double-Blind Trial.

Objective:Indoor athletes have been shown to be prone to vitamin D3 deficiency. The aim of the study was to examine the acute effects of vitamin D supplementation on muscle function using isokinetic dynamometry. Design:Randomized placebo-controlled, double-blind study. Setting:Institutional. Participants:Adult male white national level judoka athletes (n = 22) who were involved in full-time training. Exclusion criteria were vitamin supplementation, overseas travel to sunny climes, and/or an injury incurred during the last 3 months before testing. Interventions:Subjects were randomly allocated to the treatment (150 000IU vitamin D3) or placebo and given blinded supplements by an independent researcher. Participants were tested twice, 8 days apart, on a Monday morning before the start of judo training and after 2 days of rest. A 5 to 7 mL of blood sample was collected followed by isokinetic concentric quadriceps and hamstring muscle function assessments on the right leg at 30 and 200°·s−1. Main Outcome Measures:Repeated-measures analysis of variance was used to analyze isokinetic muscle force and serum 25(OH)D3. Regression to the mean was used to examine changes in 25(OH)D3 levels over the study period. Results:The treatment group demonstrated a significant increase in serum 25(OH)D levels (34%, P ⩽ 0.001) and muscle strength (13%, P = 0.01) between days 1 and 8. No significant differences were found for the placebo group for the same period. Conclusions:A single bolus of 150 000IU vitamin D3 had a significant positive effect on serum 25(OH)D levels and muscle function in vitamin D insufficient elite indoor athletes. Clinical Relevance:Serum 25(OH)D3 levels of indoor athletes should be monitored throughout the year and especially during winter months. Beneficial responses, in muscle strength and serum 25(OH)D3, to 1 dose of vitamin D3 supplementation can be observed within 1 week of ingestion. Muscle strength is linked to serum 25(OH)D levels.

Polymer film formulations for the preparation of enteric pharmaceutical capsules

Objectives Standard pharmaceutical capsules are designed to dissolve in the acidic environment of the stomach releasing the encapsulated contents for absorption. When release is required further along the gastrointestinal tract capsules can be coated with acid insoluble polymers to enable passage through the stomach and dissolution in the intestine. This paper describes formulations that have the potential to be used to produce two‐piece hard capsules for post‐gastric delivery without the requirement of an exterior coat.

Measuring the flow properties of small powder samples using an avalanche tester

ABSTRACT The feasibility of using a small-scale avalanche tester to measure the flow properties of pharmaceutical lactose powders was examined. The modes of behavior observed in larger systems were displayed and showed a clear distinction between angular, free-flowing particles and more spherical particles of similar flow characteristics. Angular Lactohale LH100 particles showed slumping behavior at a rotational frequency of 0.33 Hz that disappeared at higher frequencies. Spherical lactose powder with a similar flow function to LH100 only showed rolling behavior under the same conditions, as did more cohesive powders LH200 and LH300. Further investigation of the LH100 data using fast Fourier analysis showed that the slumping frequency was one tenth of the rotational frequency.

An in-vitro-in-vivo model for the transdermal delivery of cholecalciferol for the purposes of rodent management.

Graphical abstract