The impact of polymer mixture composition on the properties of electrospun membranes for drug delivery applications.

Orally dispersible films (ODFs) prepared by an electrospinning are a novel type of pharmaceutical formulation. This dosage form has the potential to be beneficial for small children and the elderly, who can have problems with administration of classical tablets due to the increased risk of choking and difficulty with swallowing. Due to the highly porous nanofiber morphology, the ODFs examined in this study achieve rapid disintegration into drug microparticles when in contact with saliva. The suspension is then easier to swallow. In this study, we focus on the impact of film composition (polymer matrix composition) on the properties of electrospun membranes. In particular, we prepared ODFs composed of a mixture of PEG 100 000 with HPMC E5 and PVP k90 with HPMC E5. We found significant differences in the structure of electrospinned membranes, where samples containing PEG 100 000 and HPMC E5 exhibited much narrower distribution of fibers. Furthermore, nanofibers containing PVP k90 exhibit a faster disintegration rate, while dissolution of the drug was faster in the case of PEG 100 000 containing ODFs. The improvement was caused by both the structure and composition of the membranes.

Affinity purification of serum-derived anti-IA-2 autoantibodies in type 1 diabetes using a novel MBP-IA-2 fusion protein.

Autoantibodies targeting epitopes contained within the intracellular domain (IC) of the protein phosphatase-like islet antigen 2 (IA-2) are a common marker of autoimmune type 1 diabetes (T1D), however the isolation of genuine, serum derived anti-IA-2 autoantibodies has proven challenging due to a lack of suitable bioassays. In the current study, an ELISA format was developed for affinity purification of human anti-IA-2ic autoantibodies utilizing a fusion protein (FP) incorporating maltose binding protein and the full-length IA-2IC domain. Using a T1D patient cohort validated for anti-IA-2ic autoantibodies by commercial ELISA, we demonstrate the MBP-IA-2ic FP ELISA detects serum anti-IA-2IC autoantibodies from 3 of 9 IA-2 positive patients. Further to this, a multi-plate MBP-IA-2ic FP ELISA protocol specifically affinity purifies IgG enriched for anti-IA-2ic autoantibodies. Interestingly, serum derived autoantibodies immobilised on the MBP-IA-2ic FP ELISA demonstrate increased Kappa light chain usage when compared to the respective total IgG derived from donor patients, suggesting a clonally restricted repertoire of anti-IA-2ic autoantigen specific B plasma cells is responsible for autoantibodies detect by the MBP-IA-2ic FP ELISA. This study is the first to demonstrate the generation of specific, genuine human derived anti-IA-2ic autoantibodies, thereby facilitating further investigation into the origin and functional significance of IA-2 autoantibodies in T1D.