Insulin complexes with PEGylated basic oligopeptides

Polymer Directed Protein Assemblies

“…For this a charged oligo-peptide in the form of an oligo-lysine and oligo-arginine was connected to a linear polyethylene glycol (PEG). Upon mixing of a fixed concentration of insulin with varying amounts of the cationic oligo-peptide-PEG structure, differently sized structures were obtained in the range between ~100-1800 nm with increasing amounts of cationic polymer [23]. This increase in size was associated with a reversal of surface charge going from negative for pure insulin to positive upon addition of the cationic oligo-peptide structure, which indicates coordinating and enclosing the protein.…”

“…When the polymer matrix acts as a hydrogel, the proteins are still in contact with the outside medium for small analytes and substrates because of the open porous polymeric hydrogel structure but at the same time is shielded and protected against attack by structures, which are larger than the polymer mesh-size ( Figure 7). The interactions for confinement of the protein inside the polymer gel-particle can be electrostatic as well as hydrophobic interactions or covalently bound as discussed earlier [16,22,23]. Due to a change in environment, a triggered release can be induced, e.g., a lowering of pH as is seen in cancer cells, temperature in case of local inflammation or just general biodegradability by hydrolysis or via enzymatic degradation.…”

Uniform mPEG‐b‐PMETAC enables pH‐responsive delivery of insulin

“…Similar studies on insulin complexation with cationic polymers generally obtained a complexation efficiency of 85 to 100%. 14,23,24 DLS measurements showed that the typical particle size in the mixture solutions varied from 100 to 800 nm under different conditions. The size distribution at pH 7.0 without the addition of NaCl is shown in Figure 3.…”

“…Tsiourvas et al reported that oligolysine or oligoarginine, other types of biocapatible polycations which form complexes with proteins, failed to protect insulin from trypsin degradation. 23 With regard to chymotrypsin which has 7 cleavage sites on insulin molecules [Supporting Information Figure S3(b)] (5 on the surface and 2 in the hydrophobic core), 20 a more comprehensive inhibition may require a larger mPEG-b-PMETAC polymer to shield all cleavage sites. In addition, chymotrypsin with pI of 8.1-8.6 is very weakly charged at pH 5 8, thus the electrostatic repulsive force between the polymer and chymotrypsin is much weaker, compared to that between the polymer and trypsin.…”

Wrap-and-Strip Technology of Protein–Polyelectrolyte Complex for Biomedical Application

“…Chitosan-coated mesoporous silicon microparticles are a biodegradable material with the binding capacity of insulin and albumin [87,88]. Cationic polymers of PEGylated oligolysine and oligoarginine can bind to insulin with high (>95%) levels of complex formation efficiency [89]. The PEGylated oligopeptides also have the advantage of being biodegradable, but they tend to form aggregates with insulin, as analyzed by isothermal titration calorimetry and Fourier transform infrared spectroscopy.…”