Laser-engineered dissolving microneedle arrays for protein delivery: potential for enhanced intradermal vaccination

OBJECTIVES: We aimed to highlight the utility of novel dissolving microneedle (MN)-based delivery systems for enhanced transdermal protein delivery. Vaccination remains the most accepted and effective approach in offering protection from infectious diseases. In recent years, much interest has focused on the possibility of using minimally invasive MN technologies to replace conventional hypodermic vaccine injections.

METHODS: The focus of this study was exploitation of dissolving MN array devices fabricated from 20% w/w poly(methyl vinyl ether/maleic acid) using a micromoulding technique, for the facilitated delivery of a model antigen, ovalbumin (OVA).

KEY FINDINGS: A series of in-vitro and in-vivo experiments were designed to demonstrate that MN arrays loaded with OVA penetrated the stratum corneum and delivered their payload systemically. The latter was evidenced by the activation of both humoral and cellular inflammatory responses in mice, indicated by the production of immunoglobulins (IgG, IgG1, IgG2a) and inflammatory cytokines, specifically interferon-gamma and interleukin-4. Importantly, the structural integrity of the OVA following incorporation into the MN arrays was maintained.

CONCLUSION: While enhanced manufacturing strategies are required to improve delivery efficiency and reduce waste, dissolving MN are a promising candidate for 'reduced-risk' vaccination and protein delivery strategies.

Correlates of food choice in unemployed young people: The role of demographic factors, self-efficacy, food involvement, food poverty and physical activity

Associations between socio-demographic and psychological factors and food choice patterns were explored in unemployed young people who constitute a vulnerable group at risk of poor dietary health. Volunteers (N = 168), male (n = 97) and female (n = 71), aged 15–25 years were recruited through United Kingdom (UK) community-based organisations serving young people not in education training or employment (NEET). Survey questionnaire enquired on food poverty, physical activity and measured responses to the Food Involvement Scale (FIS), Food Self-Efficacy Scale (FSS) and a 19-item Food Frequency Questionnaire (FFQ). A path analysis was undertaken to explore associations between age, gender, food poverty, age at leaving school, food self-efficacy (FS-E), food involvement (FI) (kitchen; uninvolved; enjoyment), physical activity and the four food choice patterns (junk food; healthy; fast food; high fat). FS-E was strong in the model and increased with age. FS-E was positively associated with more
frequent choice of healthy food and less frequent junk or high fat food (having controlled for age, gender and age at leaving school). FI (kitchen and enjoyment) increased with age. Higher FI (kitchen) was associated with less frequent junk food and fast food choice. Being uninvolved with food was associated with
more frequent fast food choice. Those who left school after the age of 16 years reported more frequent physical activity. Of the indirect effects, younger individuals had lower FI (kitchen) which led to frequent junk and fast food choice. Females who were older had higher FI (enjoyment) which led to less frequent fast food choice. Those who had left school before the age of 16 had low food involvement (uninvolved) which led to frequent junk food choice. Multiple indices implied that data were a good fit to the model which indicated a need to enhance food self-efficacy and encourage food involvement in order to improve dietary health among these disadvantaged young people.

Tumorigenesis and peritoneal colonization from fallopian tube epithelium

Ovarian cancer is the most lethal gynecological malignancy, primarily because its origin and initiation factors are unknown. A secretory murine oviductal epithelial (MOE) model was generated to address the hypothesis that the fallopian tube is an origin for high-grade serous cancer. MOE cells were stably altered to express mutation in p53, silence PTEN, activate AKT, and amplify KRAS alone and in combination, to define if this cell type gives rise to tumors and what genetic alterations are required to drive malignancy. Cell lines were characterized in vitro and allografted into mice. Silencing PTEN formed high-grade carcinoma with wide spread tumor explants including metastasis into the ovary. Addition of p53 mutation to PTEN silencing did not enhance this phenotype, whereas addition of KRAS mutation reduced survival. Interestingly, PTEN silencing and KRAS mutation originating from ovarian surface epithelium generated endometrioid carcinoma, suggesting that different cellular origins with identical genetic manipulations can give rise to distinct cancer histotypes. Defining the roles of specific signaling modifications in tumorigenesis from the fallopian tube/oviduct is essential for early detection and development of targeted therapeutics. Further, syngeneic MOE allografts provide an ideal model for pre-clinical testing in an in vivo environment with an intact immune system.