Novel formulations for antigen delivery using biodegradable polymers: new approaches for the use of new and established adjuvants

The use of immunological adjuvants has been established since 1924 and ever since many candidates have been extensively researched in vaccine development. The controlled release of vaccine is another area of biotechnology research, which is advancing rapidly with great potential and success. Encapsulation of peptide and protein drugs within biodegradable microspheres has been amongst the most successful of approaches within the past decade. The present studies have focused on combining the advantages of microsphere delivery systems composed of biodegradable polylactide (PLLA) and polylactide-co-glycolide (PLGA) polymers with that of safe and effective adjuvants. The research efforts were directed to the development of single-dose delivery vehicles which, can be manufactured easily, safely, under mild and favourable conditions to the encapsulated antigens. In pursuing this objective non ionic block copolymers (NIBCs) (Pluronics@ LI01 and L121) were incorporated within poly-dl-lactide (PDLA) micorospheres prepared with emulsification-diffusion method. LI0I and L121 served both as adjuvants and stabilising agents within these vaccine delivery vehicles. These formulations encapsulating the model antigens lysozyme, ovalbumin (OVA) and diphtheria toxoid (DT) resulted in high entrapment efficiency (99%), yield (96.7%) and elicited high and sustained immune response (IgG titres up to 9427) after one single administration over nine months. The structural integrity of the antigens was preserved within these formulations. In evaluating new approaches for the use of well-established adjuvants such as alum, these particles were incorporated within PLLA and PLGA microspheres at much lesser quantities (5-10 times lower) than those contained within conventional alum-adsorbed vaccines. These studies focused on the incorporation of the clinically relevant tetanus toxoid (TT) antigen within biodegradable microspheres. The encapsulation of both alum particles and TT antigen within these micropheres resulted in preparations with high encapsulation efficiency (95%) and yield (91.2%). The immune response to these particles was also investigated to evaluate the secretion of serum IgG, IgG1, IgG2a and IgG2b after a single administration of these vaccines. The Splenic cells proliferation was also investigated as an indication for the induction of cell mediated immunity. These particles resulted in high and sustained immune response over a period of 14 months. The stability of TT within particles was also investigated under dry storage over a period of several months. NIBC microspheres were also investigated as potential DNA vaccine delivery systems using hepatitis B plasmid. These particles resulted in micro spheres of 3-5 μm diameter and were shown to preserve the integrity of the encapsulated (27.7% entrapment efficiency) hepatitis B plasmid

Economic evaluation of early administration of prednisolone and/or aciclovir for the treatment of Bell's palsy

Objectives. Bell's palsy (BP), which causes facial paralysis, affects 11-40 people per 100 000 per annum in the UK. Its cause is unknown but as many as 30% of patients have continuing facial disfigurement, psychological difficulties and occasionally facial pain. We present an randomised controlled trial (RCT)-based economic evaluation of the early administration of steroids (prednisolone) and/or antivirals (acyclovir) compared to placebo, for treatment of BP. Methods. The RCT was not powered to detect differences in the cost-effectiveness; therefore, we adopted a decision analytic model approach as a way of gaining precision in our cost-effectiveness comparisons [e.g. prednisolone only (PO) versus acyclovir only versus prednisolone and acyclovir versus placebo, prednisolone versus no prednisolone (NP) and acyclovir versus no acyclovir]. We assumed that trial interventions affect the probability of being cured/not cured but their consequences are independent of the initial therapy. We used the percentage of individuals with a complete recovery (based on House-Brackmann grade = 1) at 9 months and Quality Adjusted Life Years (e.g. derived on responses to the Health Utilities Index III) as measures of effectiveness. Other parameter estimates were obtained from trial data. Results. PO dominated-i.e. was less costly and more effective-all other therapy strategies in the four arms model [77% probability of cost-effective (CE)]. Moreover, Prednisolone dominated NP (77% probability of being CE at £30 000 threshold) while no acyclovir dominated aciclovir (85% chance of CE), in the two arms models, respectively. Conclusions. Treatment of BP with prednisolone is likely to be considered CE while treatment with acyclovir is highly unlikely to be considered CE. Further data on costs and utilities would be useful to confirm findings.</p

In search of belonging: Reflections by transracially adopted people

Transracial adoption has provoked much polarised commentary, initiated heated debate and stirred up strong feelings. Yet the experience of transracially adopted people themselves remains on the margins and has rarely been given a voice. Through a series of intensely moving testimonies, In search of belonging conveys the complexity for black and minority ethnic children of being raised by a white adoptive family. It demonstrates the lifelong impact of transracial adoption and illustrates that to view such placements in either positive or negative terms is far too simplistic. The themes of separation and loss, the search for identity and belonging permeate these accounts, but so does the power of healing and survival, happiness and hope. A wide range of experiences is described, including racism during childhood, placement disruption, visiting country or origin, reclaiming cultural heritage, searching for birth mothers, fathers and other relatives, becoming a parent, involvement with the psychiatric system and connecting with other transracial adoptees. This highly original anthology brings together established writers, new and emerging writers and those who have never been published before. Through poetry, art, autobiography, memoir and oral testimony over 50 transracially adopted people tell it like it was, and is, for them. The contributors range in age from six to 56 years and were born and adopted both in the UK and countries as different as Kenya and Hong Kong, Cambodia, Sri Lanka and El Salvador. As well as a Foreword by acclaimed poet Lemn Sissay, the book includes a substantial introduction and a comprehensive resource section. In search of belonging is for all transracially adopted young people and adults. It will also be of interest to other adoptees, birth relatives, adoptive parents, prospective adoptive parents, social workers, social work students, family placement workers, counsellors, therapists, mental health and other professionals