Formulation and Evaluation of Transdermal Patches Containing BGP-15.

BGP-15 is an active ingredient with many advantages, e.g., beneficial cardiovascular and anti-inflammatory effects. The transdermal administration of BGP-15 has great potential, which has not been investigated yet, despite the fact that it is a non-invasive and safe form of treatment. The aim of our study was to formulate transdermal patches containing BGP-15 and optimize the production with the Box-Behnken design of experiment. The most optimal formulation was further combined with penetration enhancers to improve bioavailability of the active ingredient, and the in vitro drug release and in vitro permeation of BGP-15 from the patches were investigated. FTIR spectra of BGP-15, the formulations and the components were also studied. The most optimal formulation based on the tested parameters was dried for 24 h, with 67% polyvinyl alcohol (PVA) content and low ethanol content. The selected penetration enhancer excipients were not cytotoxic on HaCaT cells. The FTIR measurements and SEM photography proved the compatibility of the active substance and the vehicle; BGP-15 was present in the polymer matrix in dissolved form. The bioavailability of BGP-15 was most significantly enhanced by the combination of Transcutol and Labrasol. The in vitro permeation study confirmed that the formulated patches successfully enabled the transdermal administration of BGP-15.

Association of myasthenia gravis with polymorphisms in the gene of histamine N-methyltransferase.

INTRODUCTION: Histamine N-methyltransferase (HNMT) is the main metabolizing enzyme of histamine. Histamine modulates immune responses and plays a role in the pathogenesis of autoimmune disorders. METHODS: The non-synonymous HNMT C314T polymorphism and the A939G single-nucleotide polymorphism (SNP) influencing HNMT mRNA stability were genotyped in 213 patients with myasthenia gravis (MG) and 342 healthy controls. RESULTS: The carrier frequency of the A allele of the A939G SNP was over-represented among patients with anti-AchR and anti-Titin antibodies (P = 0.05 and P = 0.004, respectively); the presence of the minor G allele was protective against anti-AchR and anti-Titin positive MG (OR = 0.67 and OR = 0.54, respectively). The combination of the G allele carrier status with wild-type C314C homozygosity was also protective against MG (OR = 0.55, P = 0.008) and against the development of anti-AchR antibodies (OR = 0.37, P = 0.01). DISCUSSION: The A939G HNMT polymorphism is associated with autoimmune MG, while no association with C314T SNP was found.

Enzyme replacement therapy induces T-cell responses in late-onset Pompe disease.

INTRODUCTION: Enzyme replacement therapy (ERT) in ultra-orphan Pompe disease generates anti-rhGAA antibodies, which may interfere with efficacy. METHODS: rhGAA-specific T-cell responses were examined at different time-points in 6 Hungarian patients treated with rhGAA and compared with 1 untreated patient and 5 healthy controls. RESULTS: The ex vivo percentage of activated T cells was increased in treated patients. rhGAA stimulation in vitro generated a dose-dependent increase in intracellular interferon-gamma (IFN-γ) expression in CD4(+) and CD8(+) T cells. Isolated CD4(+) and CD8(+) T cells produced increased amounts of IFN-γ and tumor necrosis factor-alpha (TNF-α) in half of the patients after in vitro stimulation with rhGAA, whereas interleukin (IL)-4, IL-6, and IL-17 levels were not elevated. Expression of cytotoxic FasL and perforin molecules by natural killer (NK), NKT-like, and CD8(+) T cells were not increased ex vivo. CONCLUSIONS: We found that enzyme replacement therapy (ERT) induces pro-inflammatory T-cell responses in addition to the antibody response in Pompe disease.