• Home
  • Michael Hinchcliffe
Michael Hinchcliffe

Michael Hinchcliffe
Paracelsis Ltd

BSc (Hons), MSc, PhD

About

27
Publications
7,005
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
2,996
Citations
Additional affiliations
August 1989 - September 2012
Archimedes Development Ltd.
Position
  • Biological Group Head

Publications

Publications (27)
Article
Full-text available
Recent evidence indicates that local immune responses and tissue resident memory T cells (T RM) are critical for protection against respiratory infections but there is little information on the contributions of upper and lower respiratory tract (URT and LRT) immunity. To provide a rational basis for designing methods for optimal delivery of vaccine...
Preprint
Full-text available
Recent evidence indicates that local immune responses and tissue resident memory T cells (TRM) are critical for protection against respiratory infections but there is little information on the contributions of upper and lower respiratory tract (URT and LRT) immunity. To provide a rational basis for designing methods for optimal delivery of vaccines...
Article
Full-text available
Nasal delivery of large peptides such as parathyroid 1-34 (PTH 1-34) can benefit from a permeation enhancer to promote absorption across the nasal mucosa into the bloodstream. Previously, we have published an encouraging bioavailability (78%), relative to subcutaneous injection in a small animal preclinical model, for a liquid nasal spray formulati...
Article
Full-text available
Abstract: Amyotrophic lateral sclerosis (ALS) is the commonest form of motor neuron disease and is a fatal, degenerative, multisystem disorder affecting upper and/or lower motor neurons in the motor cortex, brain stem, and spinal cord. ALS is characterized by progressive atrophy of associated bulbar, limb, thoracic, and abdominal muscles and suppor...
Article
Full-text available
We investigated the protective efficacy of two intranasal chitosan (CSN and TM-CSN) adjuvanted H5N1 Influenza vaccines against highly pathogenic avian Influenza (HPAI) intratracheal and intranasal challenge in a ferret model. Six groups of 6 ferrets were intranasally vaccinated twice, 21 days apart, with either placebo, antigen alone, CSN adjuvante...
Chapter
Nasal vaccination offers a number of attractions, including the potential for generating mucosal and systemic antibody responses and the avoidance of syringes and needles for dosing. However, many antigens are not capable by themselves of eliciting an adequate immune response when administered intranasally and coadministration with an adjuvant will...
Article
Full-text available
The nasal route is attractive for the delivery of vaccines in that it not only offers an easy to use, non-invasive, needle-free alternative to more conventional parenteral injection, but it also creates an opportunity to elicit both systemic and (crucially) mucosal immune responses which may increase the capability of controlling pathogens at the s...
Article
Full-text available
Please cite this paper as: Svindland et al. (2012) A study of Chitosan and c‐di‐GMP as mucosal adjuvants for intranasal influenza H5N1 vaccine. Influenza and Other Respiratory Viruses 10.1111/irv.12056000(000), 000–000. Background Highly pathogenic avian influenza A/H5N1 virus remains a potential pandemic threat, and it is essential to continue va...
Article
Here we confirm that intranasal (IN) dry powder anthrax vaccine formulations are able to protect rabbits against aerosol challenge 9 weeks after a single immunization. The optimum dose of rPA in our dry powder anthrax vaccine formulation in rabbits was experimentally determined to be 150microg and therefore was chosen as the target dose for all sub...
Article
An intranasal vaccine targeting the Bacillus anthracis toxin and vegetative bacterium was tested for the ability to protect immunized rabbits against aerosol B. anthracis spore exposure. Rabbits were vaccinated intranasally with PA-based vaccines formulated as dry powders with or without chitosan (ChiSys, Archimedes Development Limited), a compound...
Article
Full-text available
The effectiveness of chitosan in promoting the intranasal bioavailability of recombinant human growth hormone (hGH) has been evaluated. hGH was formulated with chitosan to produce a powder blend (Formulation A) and granules (Formulation B) for intranasal administration. The in vivo pharmacokinetic performance of the formulations was evaluated in a...
Article
The effects of a chitosan-based delivery system on the pharmacokinetics of intranasally administered salmon calcitonin (sCT) were investigated in a sheep model. In particular, the feasibility of producing a formulation with a comparable or improved bioavailability and/or less variability than the currently marketed nasal product (Miacalcin nasal sp...
Article
Full-text available
Paclitaxel is a highly promising phase-sensitive antitumor drug that could conceivably be improved by extended lower dosing as opposed to intermittent higher dosing. Although intratumoral delivery of paclitaxel to the whole tumor at different loads and rates has already been achieved, determining an optimal release mode of paclitaxel for tumor erad...
Article
Investigate the effect of blood sampling site and physicochemical characteristics of drugs on the pharmacokinetic (PK) parameters obtained after intravenous and nasal administration in sheep and compare results with computer simulations. Three drugs, insulin, morphine, and nicotine, were administered nasally and by intravenous (IV) injection to she...
Article
To investigate whether the widely accepted advantages as sociated with the use of chitosan as a nasal drug delivery system might be further improved by application of chitosan formulated a nanoparticles. Insulin-chitosan nanoparticles were prepared by the ionotropic gelation of chitosan glutamate and tripolyphosphate pentasodium and by simple compl...
Article
Full-text available
Morphine administered nasally to humans as a simple solution is only absorbed to a limited degree, with a bioavailability of the order of 10% compared with intravenous administration. This article describes the development of novel nasal morphine formulations based on chitosan, which, in the sheep model, provide a highly increased absorption with a...
Article
A novel nasal formulation, in the form of a nicotine-Amberlite resin complex powder has been developed that provided an optimal combined pulsatile and sustained plasma nicotine profile for smoking cessation. The adsorption isotherms of nicotine hydrogen tartrate salt on two types of Amberlite resins (IRP69 and IR120) were evaluated and the subseque...
Article
A variety of different types of nasal vaccine systems has been described to include cholera toxin, microspheres, nanoparticles, liposomes, attenuated virus and cells and outer membrane proteins (proteosomes). The present review describes our work on the use of the cationic polysaccharide, chitosan as a delivery system for nasally administered vacci...
Article
This paper describes the clearance characteristics of two bioadhesive nasal delivery systems in the form of chitosan microspheres and chitosan solution, from the nasal cavity of conscious sheep. The pattern of deposition and clearance of the nasal dosage forms were evaluated using a radioactive tracer and the non-invasive technique of gamma scintig...
Article
Full-text available
The gastrointestinal transit of liquid, pellet and tablet formulations was measured under fasted conditions in the domestic pig (n = 4) using the technique of gamma scintigraphy. The mean times for 50% gastric emptying for liquid and pellet systems were 1.4 and 2.2 h, respectively; tablets emptied between 1.5 and 6.0 h. Total transit times were in...
Article
Full-text available
We have evaluated the ability of two carbohydrate biopolymers, chitosan and gellan, to enhance antibody responses to subunit influenza virus vaccines delivered to the respiratory tracts of mice. Groups of mice were vaccinated three times intranasally (i.n.) with 10 microg of purified influenza B/Panama virus surface antigens (PSAs), which consist o...
Article
Intranasal insulin delivery has been widely investigated as an alternative to subcutaneous injection for the treatment of diabetes. The pharmacokinetic profile of intranasal insulin is similar to that obtained by intravenous injection and, in contrast to subcutaneous insulin delivery, bears close resemblance to the `pulsatile' pattern of endogenous...
Article
Chitosan is a polysaccharide that demonstrates much potential as a gene delivery system. The ability of a commercially available chitosan and depolymerized chitosan oligomers to condense plasmid was determined using TEM and microtitration calorimetry, while the diameter and stability of the resultant complexes were measured using laser light scatte...
Article
This study was designed to investigate the existence of an ileal brake mechanism in the pig model. The test substances used (oleic acid, deoxycholic acid, taurocholic acid) had all been previously shown to affect the ileal brake mechanism in other species including man. The substances were infused directly into the terminal ileum of surgically modi...
Article
The distribution and the retention time of a novel bioadhesive intravaginal delivery system based on HYAFF microspheres were studied in a sheep model. In a preliminary experiment, the vagina of the ewe was outlined by gamma scintigraphy following vaginal administration of a radiolabelled gel and this data was used as a reference for subsequent eval...
Article
The findings of this project have added to the pool of information reported in the literature regarding the application of the nasal route for the delivery of insulin and other peptide drugs. The preliminary studies reported in this project were apparently the first studies performed to investigate the potential use of chitosan in nasal delivery sy...
Article
An in vivo rat model was used to study the nasal absorption of insulin in the presence of selected enhancers (Laureth 9, glycodeoxycholate and L-α-lysophosphatidylcholine) either alone or in combination with 2-hydroxypropyl-β-cyclodextrin or γ-cyclodextrin. All the enhancers when administered alone with insulin produced about 50% decrease in the bl...

Network

Cited By

Projects

Project (1)
Archived project
Current Drug Delivery projects focus on in vivo evaluation of the efficacy (pharmacokinetics, immunology etc.) and safety/tolerability of various novel dosage forms including: Intravaginal ring in sheep; nasal/oral vaccine in rat/rabbit; nasal polypeptide in sheep; nasal corticosteroid in sheep; ocular (intravitreal) mAB in rabbits. Risk Assessment projects, include evaluation and qualification of impurity levels in drug substance/product and on extractables/leachables