Norfloxacin-Poly(_l-Lysine Citramide Imide) Conjugates and Structure-dependence of the Drug Release

Abstract

Norfloxacin (Nflx), an antibiotic which is active against some intracellular bacteria, was coupled to a polymeric carrier, namely poly(L-lysine citramide) via a lysine or an ethylcarbamate spacer to obtain a macromolecular prodrug. The carrier, which derived from the two metabolites citric acid and L-lysine, is known to be biocompatible and slowly degradable under slight acidic conditions. Conjugates were characterised by UV, 1H and 13C NMR and SEC. The presence of Norfloxacin and the lysine type spacer caused chain aggregation, due to a probable physical cure. The release of Norfloxacin from these prodrugs and from a prodrug where Norfloxacin is bound to the carrier backbone without spacer arm was investigated comparatively in vitro. Conjugation via a carbamate-type linkage appeared as a method to achieve the release of Norfloxacin from a PLCA-type conjugate at neutral.

Polypeptide‐Based Conjugates as Therapeutics: Opportunities and Challenges

“…This may be due to electrostatic interactions between the residual primary amine group and the carboxyl groups present as pendent groups along the polymer chain or covalent amide bonds between amine and carboxylic acid groups. The carbamate space did not lead to detectable levels of aggregation …”

Antibiotic-containing polymers for localized, sustained drug delivery

“…In another example, NOR was conjugated to a poly(L-lysine citramide) carrier [29] using three different methodologies with 1) a lysine spacer, 2) an ethyl carbamate spacer, and 3) no spacer between drug and backbone. Firstly, dibenzyloxycarbonyl-L-lysine was coupled to NOR via DCC reaction; subsequently, the product was reacted with HBr to remove the protecting group and generate the hydrobromide which was then reacted with poly(L-lysine citramide imide) and dialyzed to generate the final product in which an amide bond links the drug to the polymer backbone with a lysine spacer.…”

Low-fouling, mixed-charge poly-l-lysine polymers with anionic oligopeptide side-chains

“…Because PLL is positively charged at physiological pH, it can be easily adsorbed on a large variety of negatively charged substrates via electrostatic interactions, including glass, 36 metals, 37 polymers, 38 and metallic oxides. 39 Furthermore, PLL polymers can be easily modified with nonionic side-chains (like PEG/OEG), thereby making it an ideal candidate for engineering biomaterial interfaces, such as surface coatings, 37,40 drug, 41 gene, 42 and protein 43 delivery platforms, and hydrogel scaffolds. 44 The easy functionalization of PLL polymers with different functional groups allows to have a critical control over the biosensing interfaces by creating mixed monolayers with different functionalities.…”