Degradation Mechanism and Kinetics of Thermosensitive Polyacrylamides Containing Lactic Acid Side Chains

Abstract

Diblock copolymers of poly(N-isopropylacrylamide-co-N-(2-hydroxypropyl)methacrylamide lactate) (poly(NIPAAm-co-HPMAm-lactate)) as a thermosensitive block and poly(ethylene glycol) (PEG) as a hydrophilic block form polymeric micelles above the cloud point (CP) of the temperature-sensitive block. Destabilization of these micelles occurs upon hydrolysis of the lactate side chains. Here we report on the degradation kinetics of the HPMAm-mono(di)lactate monomers and their copolymers with NIPAAm. The degradation of the monomers and polymers in their soluble state (thus below their CP) followed normal ester hydrolysis behavior: the degradation rate increased with temperature, pH (from pH 7.5 to 11), and dielectric constant of the medium. Above the CP, where the polymers are in a precipitated state, a significant retardation of the polymer degradation occurred due to a decrease of dielectric constant of the local environment of the precipitated polymer. This study shows that it is possible to predict the rate of formation of HPMAm in NIPAAm-co-HPMAm-lactate copolymers which results in an increase of the overall hydrophilicity of the polymers and destabilization of polymeric micelles based on poly(NIPAAm-co-HPMAm-lactate).

Photopolymerized Thermosensitive Poly(HPMAlactate)-PEG-Based Hydrogels: Effect of Network Design on Mechanical Properties, Degradation, and Release Behavior

“…The degradation mechanism of p(HPMAm-lac)-PEG-based hydrogels is due to hydrolysis of the numerous ester bonds present in the polymer networks, as described earlier. 37,41 It was shown that the lactate side chains of p(HPMAm-lac) with a free terminal OH group are hydrolyzed in approximately 1 week. The terminal lactate moiety in the HPMAm-dilactate is degraded faster than the one in the HPMAm-monolactate, because by a nucleophilic attack of the hydroxy terminus, the ester bond that is located two lactate units further on in the side chain is hydrolyzed in a so-called backbiting mechanism.…”

The effect of the processing and formulation parameters on the size of nanoparticles based on block copolymers of poly(ethylene glycol) and poly(N-isopropylacrylamide) with and without hydrolytically sensitive groups

“…The PEG 2 -ABCPA macroinitiators with PEG 2000, PEG 5000 and PEG 10 000 were prepared as described previously [34]. HPMA-dilactate was obtained as reported by Neradovic et al [38].…”

Fluorophore Labeling of Core-Crosslinked Polymeric Micelles for Multimodal In Vivo and Ex Vivo Optical Imaging

“…The size (Z ave ) and light scattering intensity (LSI) of the micelles were monitored by DLS while cooling a micellar suspension from 25 to 2 °C in 90 min. [15] Hydrolytic stability was analyzed by monitoring the Z ave and the LSI of the micelles with DLS under accelerated hydrolytic conditions (pH 10.0 and 37 °C) for 22 h. [16,47,48] The pH of the micellar dispersion was adjusted to pH 10.0 by diluting the micellar dispersion 5-fold with 500 mM Na 2 CO 3 /NaHCO 3 pH 10.0 buffer. The integrity of the CCPM against the dissolution by DMF was performed and also to examine the amount of non-crosslinked free polymer chains in the CCPM dispersion.…”

“…This value is in line with other published papers, in which the target site accumulation of micelles (as well as other nanocarriers) was evaluated using optical and radionuclide-based imaging techniques. [28,[43][44][45][46][47][48] Figure 5C also provides feedback on the accumulation of the iCCPM in several different healthy tissues. The liver uptake of the iCCPM was found to be ~20% at 48 h p.i., which corresponds with previous reports, and results from clearance by the mononuclear phagocytic system (MPS).…”