Dissolving Microneedle Delivery of Nanoparticle Encapsulated Antigen Elicits Efficient Cross-Priming and Th1 Immune Responses by Murine Langerhans Cells

Dendritic cells (DCs) of the skin play an important role in skin-mediated immunity capable of promoting potent immune responses. We availed of polymeric dissolving microneedle (MN) arrays laden with nano-encapsulated antigen to specifically target skin DC networks. This modality of immunization represents an economic, efficient and potent means of antigen delivery directly to skin DCs, which are inefficiently targeted by more conventional immunization routes. Following MN immunization, Langerhans cells (LCs) constituted the major skin DC subset capable of cross-priming antigen-specific CD8(+) T cells ex-vivo. While all DC subsets were equally efficient in priming CD4(+) T cells, LCs were largely responsible for orchestrating the differentiation of CD4(+) IFN-γ and IL-17 producing effectors. Importantly, depletion of LCs prior to immunization had a profound effect on CD8(+) CTL responses in vivo, and vaccinated animals displayed reduced protective anti-tumour and viral immunity. Interestingly, this cross-priming bias was lost following MN immunization with soluble antigen, suggesting that processing and cross-presentation of nano-particulate antigen is favoured by LCs. Therefore, these studies highlight the importance of LCs in skin immunization strategies and that targeting of nano-particulate immunogens through dissolvable polymeric MNs potentially provides a promising technological platform for improved vaccination strategies.Journal of Investigative Dermatology accepted article preview online, 22 September 2014. doi:10.1038/jid.2014.415.

Potential of Microneedles in Enhancing Delivery of Photosensitising Agents for Photodynamic Therapy

Photodynamic therapy can be used in the treatment of pre-malignant and malignant diseases. It offers advantages over other therapies currently used in the treatment of skin lesions including avoidance of damage to surrounding tissue and minimal or no scarring. Unfortunately, systemic delivery of photosensitising agents can result in adverse effects, such as prolonged cutaneous photosensitivity; while topical administration lacks efficacy in the clearance of deeper skin lesions and those with a thick overlying keratotic layer. Therefore, enhancement of conventional photosensitiser delivery is desired. However, the physicochemical properties of photosensitising agents, such as extreme hydrophilicity or lipophilicity and large molecular weights make this challenging. This paper reviews the potential of microneedles as a viable method to overcome these delivery-limiting physicochemical characteristics and discusses the current benefits and limitations of solid, dissolving and hydrogel-forming microneedles. Clinical studies in which microneedles have successfully improved photodynamic therapy are also discussed, along with benefits which microneedles offer, such as precise photosensitiser localisation, painless application and reduction in waiting times between photosensitiser administration and irradiation highlighted.

Supporting delivery of the recovery package for people living with and beyond cancer

Survivorship is an important issue in cancer care in the UK. More people are being diagnosed with the disease and many more are living for longer after diagnosis. The National Cancer Survivorship Initiative recommends that patients with cancer have a package of care designed to improve outcomes and support for those living with and beyond the disease. The recovery package consists of a holistic needs assessment, treatment summary, cancer care review and health and wellbeing event. Although these interventions are recommended as a way to improve care, many people do not have access to the combined package, or even some of its components. The Cancer Nursing Partnership (CNP), a collaboration of cancer nursing organisations and communities of influence, has been established to support nurses with delivery of the recovery package in practice. This article describes the package and its components, introduces the CNP and outlines the work it has carried out to date.

Evaluation of Multidisciplinary Delivery of Surgical Anatomy Teaching

Title Evaluation of Multidisciplinary Delivery of Surgical Anatomy Teaching

Authors Walsh I.K., Taylor S.J., Dorman A, Boohan M.

Objectives To evaluate the efficacy of newly introduced multidisciplinary methods to deliver Surgical Anatomy teaching to undergraduate medical students.

Design and Setting Qualitative and quantitative study using questionnaires and focus groups, employing students of the perioperative and emergency medicine (POEM) module of the phase 4 undergraduate medical curriculum at Queen’s University Belfast.

Outcome Measures To determine:
(1) if multidisciplinary teaching is effective in delivering surgical anatomy teaching,
(2) student’s learning preferences regarding this teaching method.
Results The questionnaire response rate was 89% (216 of 244 students; female: male ratio 1.25) and 42 students participated in 6 focus groups. Mean questionnaire responses indicated a favourable opinion on quality assurance items and multidisciplinary teaching. 81% of students agreed that multidisciplinary teaching enhanced learning and 86% felt that this did not adversely affect interaction. A positive contribution towards POEM learning was reported for Radiology (95% of students), Anatomy (93%) and Surgery (78%). The benefits of multidisciplinary teaching were congruent for Anatomy, Radiology and Surgery with 78% of students indicating a perceived favourable association with learning. Multidisciplinary teaching was not associated with diluted interaction, with 62% of students describing interaction as sufficient. 88% of students positively ranked tutor characteristics of enthusiasm and encouragement as being strongly associated with teacher quality. Positive perception of overall quality was strongly associated with learning preferences as well as more generic quality assurance issues (80% students; alpha coefficient 0.83).
The results were supported by triangulation of the above quantitative data with qualitative data generated by the focus groups. Whilst students frequently misunderstood the meaning of “multidisciplinary teaching”, there was an appreciation of the method’s worth; students recognised and valued the relevance of Anatomy, Radiology and Surgery teaching to POEM learning. The importance of vertically integrating Anatomy into all stages of the undergraduate curriculum was especially recognised.

Reference Aarnio M, Nieminen J, Pyorala E, Lindbolm-Ylanne S. Motivating medical students to learn. 2010 Med Teach;32(4):199-204.

Immunogenetic responses in calves to intranasal delivery of bovine respiratory syncytial virus (BRSV) epitopes encapsulated in poly (DL-lactide-co-glycolide) microparticles

Bovine respiratory syncytial virus (BRSV) is the principal aetiological agent of the bovine respiratory disease complex. A BRSV subunit vaccine candidate consisting of two synthetic peptides representing putative protective epitopes on BRSV surface glycoproteins in soluble form or encapsulated in poly(lactide-co-glycolide) (PLG) microparticles were prepared. Calves (10 weeks old) with diminishing levels of BRSV-specific maternal antibody were intranasally administered a single dose of the different peptide formulations. Peptide-specific local immune responses (nasal secretion IgA), but not systemic humoral (serum IgG) or cellular responses (serum IFN-γ), were generated by all forms of peptide. There was a significant reduction in occurrence of respiratory disease in the animals inoculated with all peptide formulations compared to animals given PBS alone. Furthermore no adverse effects were observed in any of the animals post vaccination. These results suggest that intranasal immunisation with the peptide subunit vaccine does induce an as yet unidentified protective immune response.