Insulin-loaded poly(acrylic acid)-cysteine nanoparticles: Stability studies towards digestive enzymes of the intestine

Abstract

This study evaluated thiolated poly(acrylic acid) nanoparticles as a valuable tool to protect insulin from degradation by serinproteases of the intestine. Nanaoparticles were characterized concerning particle size, zeta potential, and drug load. Furthermore, in vitro release studies were performed. Within in vitro degradation studies with trypsin, alpha-chymotrypsin, and elastase it could be demonstrated that the obtained nanoparticles are capable of protecting 44.47 +/- 0.89% of the initial insulin amount from tryptic degradation, 21.33 +/- 5.34% from chymotryptic degradation, and 45.01 +/- 1.40% from degradation by elastase compared to insulin solutions.

The Oral Delivery of Proteins Using Interpolymer Polyelectrolyte Complexes

“…After 60 min, thiolated PECs had only approximately 10% of their initial insulin load nondegraded, while nonthiolated PECs had approximately 25% nondegraded. This is surprising given that one expected advantage of thiolated PECs is their increased ability to protect proteins from enzymatic breakdown [32,63,[94][95][96][97]103]. Again this may refer back to the propensity for surface-functionalized PECs to form disulfides which in turn future science group may limit their ability to chelate metal cations which are responsible for enzyme activity [66].…”

“…The rapid release in pH 6.8 is surprising, given that disulfide-bond formation should be increased at a pH above 5 due to the increasing oxidation of the thiol groups on the PECs [32,63,[94][95][96][97]103]. The opposite appears to have happened whereby the interpolymer interactions have become so weak that the nanoparticles can no longer retain insulin at increasing pHs.…”

“…To date, most thiomers have relied on disulfide crosslinking within PECs to form stable particles as the pH rises to five and above [32,63,[94][95][96][97]103]. However, as mentioned above, this reduces the number of 'free' thiol groups available for mucoadhesion and enzyme inhibition.…”

“…future science group interpolymer complexes of polyanions and polycations have been produced to try and mitigate the problems of using polyanions or polycations alone [2,84,90,103].…”

Development and in vivo evaluation of a new oral nanoparticulate dosage form for leuprolide based on polyacrylic acid

“…Therefore, PVP (10,11,12) exhibiting a carboxylic moiety, and Pluronic F68 with polyether structure were chosen. In order to decide between the two polymers and to determine optimal ratios, titration experiments at varying ratios were performed and monitored by absorbance measurement at 400 nm.…”