Influence of Enzymes on the Stability of Poly Alkyl Cyanoacrylate Nanoparticles

The peroral route is the most convenient way of delivering drugs, leading to better patient compliance, especially during long-term treatment. However, many drugs, including proteins and peptides, are unstable in the gastrointestinal tract (GIT) or are insufficiently absorbed. Earlier studies have shown that cyanoacrylate nanoparticles58,59 and nanocapsules60,61 improve the absorption of several drugs like vincamin or insulin from the GIT. Maincent et al.58 demonstrated the efficiency of PBCA nanoparticles as a drug delivery system for the GIT by improving the absorption of vincamin by more than 60% compared to an equimolar solution. Investigation of the parameters that influence the stability of nanoparticles in the GIT is much more difficult because of the complexity of the GIT. The pH changes from 2.0 in the stomach to 7-8 in the small intestine. Moreover, in different parts of the GIT there are different enzymes in differing concentrations. Degradation studies with cyanoacrylate was performed as early as 1972.62 Lenaerts et al. incubated PIBCA nanoparticles in rat liver microsomes. As these microsomes contain a mixture of enzymes, it was difficult to determine which enzyme took part in the degradation process. Scherer et al.56 studied the influence of different enzymes in vitro on the stability of PBCA nanoparticles. The study used pepsin, amylase, and esterase enzymes, added in a buffer solution that contained dispersed nanoparticles. Amylase was selected because dextran is used as a stabilizer in nanopar-ticle preparation and was shown to be partially incorporated into the polymer chains.64 Esterase was selected because hydrolysis of the ester side chain is the main route of degradation of PACA nanoparticles.65 The study showed significant degradation of PBCA nanoparticles at 37°C and was dependent on the pH of the buffer solution. The addition of pepsin and amylase to the buffer solution was found to have no influence on the stability of nanoparticles. The results upon addition of amylase revealed that dextran either was not incorporated to a significant degree or that its incorporation did not alter the regular nonenzymatic or esterase-dependant degradation pathway and velocity of this polymer in the form of nanoparticles. In contrast, the esterase significantly influenced the stability of the nanoparticles. Esterase demonstrated the highest activity of nano-particle degradation at neutral pH values; as well, the degradation of PBCA nanoparticles was proportional to the amount of esterase added. These observations suggest that the degradation of PBCA nanoparticles does not occur before the particles reach the small intestine, as esterase is released by the pancreas into the lumen of the small intestine, the major site for absorption of several drugs.

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Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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