Effect of Side Groups on the Hydrolytic Stability of Thiolated and Disulfide Cross-linked Polyaspartamides

Abstract

Thiolated polyaspartamides either with N,N-dimethyl-2-aminoethyl (DME), N,N-dimethyl-3-aminopropyl (DMP) or 2-hydroxyethyl (HE) side groups were synthesized to study the effect of side groups on the hydrolytic stability of these polymers. The chemical structure of linear polymers was confirmed by 1H NMR spectroscopy, while thiol content was determined by Ellman's assay. Hydrolytic stability of thiolated polyaspartamides was studied by viscosity measurements and results suggested main-chain degradation in the presence of DME side groups. Polyaspartamides with DMP or HE side groups showed considerable stability. Thiolated polyaspartamides were converted to their disulfide cross-linked hydrogels and the gelation process was followed by oscillatory rheology. Time-dependence of dynamic moduli indicated the degradation of hydrogels containing DME side groups, while stable moduli were observed for hydrogels containing DMP or HE side groups. This structure-dependent aqueous degradation of polyaspartamides can be useful in different biomedical fields.

Nanoformulation of Therapeutic Enzymes: A Short Review

“…Various types of carriers, such as hydrogels [39], liposomes [40], and nanoparticles (NPs) [41][42][43], have been used for this purpose. Different inorganic NPs (such as, silica, iron and titan-oxide NPs), and organic NPs (for example natural and unnatural polymer NPs such as polyvinyl alcohol (PVA), polylactic acid (PLA), chitosan, polyaspatamodes) single enzyme NPs, and carbon-based NPs (such as graphene and carbon nanotubes) can all be utilized in enzyme therapy formulation [44][45][46][47][48].…”

Thiolated cationic poly(aspartamides) with side group dependent gelation properties for the delivery of anionic polyelectrolytes

“…We earlier reported that poly(aspartic acid) and polyaspartamide derivatives and their hydrogels are promising candidates as biocompatible, chemically versatile, and responsive excipients. [18][19][20][21][22][23] We also showed that the non-enzymatic degradation rate of polyaspartamide hydrogels could be controlled by the side group structure, 24 making disulfide cross-linked PASP hydrogels good candidates for human biological applications where in situ gelation and/or bioadhesion are beneficial.…”

Synthesis, Complex Formation and Corneal Permeation of Cyclodextrin-Modified, Thiolated Poly(Aspartic Acid) as Self-Gelling Formulation of Dexamethasone

“…Cyclodextrin units have already been conjugated to various macromolecular structures to obtain water-soluble polymer-based formulations or hydrogels for the efficient encapsulation of hydrophobic APIs [27]. Poly(aspartic acid) (PASP) and its thiolated form as water-soluble, biodegradable, and biocompatible poly(amino acid)s are widely studied for pharmaceutical uses [28][29][30][31][32][33]. The interest in using PASP is supported by the chemical versatility of polysuccinimide − the precursor polymer of PASP − as succinimide repeating units can react with various nucleophiles and facilitate degradation under physiological conditions depending on the composition of the pendant groups [34][35][36][37][38].…”