In Vitro Assessment of the Hydrolytic Stability of Poly(2-isopropenyl-2-oxazoline)

Abstract

Poly(2-isopropenyl-2-oxazoline) (PiPOx) is emerging as a promising, versatile polymer platform to design functional materials and particularly biomaterials that rely on the hydrophilic character of the 2-oxazoline side units. To be able to assess the applicability of PiPOx in a biomedical context, it is essential to understand its stability and degradation behavior in physiological conditions. In the present work, the hydrolytic stability of PiPOx was systematically investigated as a function of pH during incubation in various buffers. PiPOx was found to be stable in deionized water (pH 6.9), to have good stability in basic conditions (pH 8 and 9), to be satisfactorily stable in neutral conditions (pH 7.4), and to have moderate to low stability in acidic conditions (decreases drastically from pH 6 to pH 1.2). At pH 4, PiPOx formed a crosslinked network in a timeframe of hours, while at pH 1.2, PiPOx was transformed to a water-soluble poly(N-(2-hydroxyethyl)methacrylamide) type of structure over the course of 2 weeks. In vitro stability assays were performed in phosphate-buffered saline (pH 7.4), simulated body fluid (SBF) (pH 7.4), simulated saliva (pH 6.4), simulated intestinal fluid (pH 6.8), and plasma (pH 7.4) revealing that PiPOx is stable in these SBFs up to 1 week of incubation. When incubated in simulated gastric fluid (pH 1.2), PiPOx exhibited a similar degradation behavior to that observed in the buffer at pH 1.2, rendering a water-soluble structure. The presented results on the stability of PiPOx will be important for future use of PiPOx for the development of drug-delivery systems and biomedical applications, such as hydrogels.

Poly(N-allyl acrylamide) as a Reactive Platform toward Functional Hydrogels

“…When choosing a polymer platform for the preparation of hydrogels, the hydrophilicity is an important property to allow the uptake of water. A wide range of hydrophilic polymers are available including biopolymers, like alginate, − chitosan, − and gelatin, − as well as synthetic polymers, such as poly(ethylene glycol), − poly(hydroxyethyl methacrylate), − poly(vinyl alcohol), − poly(2-oxazoline)s, − polyacrylamides, − and recently poly(2-isopropenyl-2-oxazoline)s. − …”

Poly(2-isopropenyl-2-oxazoline) as a reactive polymer for materials development

“…16 Synthesis by direct condensation of isobutyronitrile with 2-amino-ethanol has been also reported. 17,18 In addition, it is worth noting that a very efficient synthesis from 2-ethyl-2-oxazoline via the formaldehyde reaction has been described previously. 19…”

“…16 Synthesis by direct condensation of isobutyronitrile with 2-amino-ethanol has been also reported. 17,18 In addition, it is worth noting that a very efficient synthesis from 2-ethyl-2oxazoline via the formaldehyde reaction has been described previously. 19 This type of five-membered heterocyclic compound can undergo various ring-opening reactions proceeding via an addition-type mechanism, as presented in Fig.…”

“…Taking into account the potential biomedical applications, the hydrolytic stability of PiPOx in various water media was systematically investigated as a function of pH. 18 Studies performed in different aqueous media show that the polymer is relatively stable in deionized water ( pH 6.9) and has good stability in basic conditions ( pH 8 and 9). 18,34 Under acidic conditions, the stability of the polymer decreases with changing pH from 6 to 1.2.…”

“…18 Studies performed in different aqueous media show that the polymer is relatively stable in deionized water ( pH 6.9) and has good stability in basic conditions ( pH 8 and 9). 18,34 Under acidic conditions, the stability of the polymer decreases with changing pH from 6 to 1.2. It has been found that the degradation process occurs via hydrolysis and crosslinking and only affects the polymer side chains, while the main chain remains intact.…”