Drug loading and release from polypeptide multilayer nanofilms
AbstractPolypeptides, linear macromolecules, are formed from amino acid residues by linkage of peptide bonds. Proteins are polypeptides too, with more complex conformations contributing to specific functionalities. Disulfide bonds are very important to maintain the structure and functions of proteins, which will form between two cysteine (Cys) residues under oxidizing circumstance.
Cys containing polypeptides are designed and synthesized by F-moc (9-Fluorenylmethyloxycarbonyl) chemistry. The number and position of Cys residues can be controlled by amino acid sequences design and following peptide synthesis, which is important to gain insights on the nature of polyelectrolyte multilayer film assembly and stability.
Both commercial and designed polypeptides have been used to fabricate multilayer nanofilms by Layer-by-layer self-assembly (LBL). The thickness, refractive index, and surface morphology of Cys containing polypeptide multilayer films can be controlled by adjusting assembly pHs over a small range, because these are affected by the deprotonation of Cys side chains and rearrangement of charge distributions. The number of Cys residues in the polypeptide chain can influence the number of disulfide bonds formed under an oxidizing environment, and furthermore affect the stability of multilayer films. The 2-D or 3-D disulfide crosslinkings can fortify the polypeptide multilayer film stabilities.
Multilayer polypeptide films made from poly-L-lysine (PLL), poly-glutamic acid (PLGA), and designed peptides have been used in methylene blue (MB) dye loading and release. The amount of MB loaded can be finely controlled by adjusting assembly pHs and architecture of polypeptide multilayers. The controlled release of MB from nanofilms could be influenced by various factors such as pH and salt concentrations of the release medium.
The side chains of Cys residues can form mixed disulfides with drugs containing thiol groups. The reversible disulfide bond can act as a switch for the redox-stimulated drug loading and release. 5,5\u27-dithiobis-(2-nitrobenzoic acid) (DTNB) has been used as a drug indicator to bind to Cys containing polypeptides covalently. Controlled release of 2-nitro-5-thiobenzoate anions (TNB 2-) from labeled polypeptides has been tested both in solution phase and solid phase-multilayer films. The new drug loading and release mechanism, the change of redox potential, provides a promising possibility for future targeted drug delivery