16 research outputs found

    Pre-formulation and systematic evaluation of amino acid assisted permeability of insulin across in vitro buccal cell layers

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    The aim of this work was to investigate alternative safe and effective permeation enhancers for buccal peptide delivery. Basic amino acids improved insulin solubility in water while 200 and 400 ”g/mL lysine significantly increased insulin solubility in HBSS. Permeability data showed a significant improvement in insulin permeation especially for 10 ”g/mL of lysine (p < 0.05) and 10 ”g/mL histidine (p < 0.001), 100 ”g/mL of glutamic acid (p < 0.05) and 200 ”g/mL of glutamic acid and aspartic acid (p < 0.001) without affecting cell integrity; in contrast to sodium deoxycholate which enhanced insulin permeability but was toxic to the cells. It was hypothesized that both amino acids and insulin were ionised at buccal cavity pH and able to form stable ion pairs which penetrated the cells as one entity; while possibly triggering amino acid nutrient transporters on cell surfaces. Evidence of these transport mechanisms was seen with reduction of insulin transport at suboptimal temperatures as well as with basal-to-apical vectoral transport, and confocal imaging of transcellular insulin transport. These results obtained for insulin is the first indication of a possible amino acid mediated transport of insulin via formation of insulin-amino acid neutral complexes by the ion pairing mechanism

    Collision Resistant Hashing for Paranoids: Dealing with Multiple Collisions

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    A collision resistant hash (CRH) function is one that compresses its input, yet it is hard to find a collision, i.e. a x1≠x2x_1 \neq x_2 s.t. h(x1)=h(x2)h(x_1) = h(x_2). Collision resistant hash functions are one of the more useful cryptographic primitives both in theory and in practice and two prominent applications are in signature schemes and succinct zero-knowledge arguments. In this work we consider a relaxation of the above requirement that we call Multi-CRH: a function where it is hard to find x1,x2,
,xkx_1, x_2, \ldots, x_k which are all distinct, yet h(x1)=h(x2)=⋯=h(xk) h(x_1) = h(x_2) = \cdots = h(x_k). We show that for some of the major applications of CRH functions it is possible to replace them by the weaker notion of an Multi-CRH, albeit at the price of adding interaction: we show a statistically hiding commitment schemes with succinct interaction (committing to poly(n)\mathsf{poly}(n) bits requires exchanging O(n)O(n) bits) that can be opened locally (without revealing the full string). This in turn can be used to provide succinct arguments for any statement. On the other hand we show black-box separation results from standard CRH and a hierarchy of such Multi-CRHs
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