Copolymers of N‐isopropylacrylamide, HEMA‐lactate and acrylic acid with time‐dependent lower critical solution temperature as a bioresorbable carrier

Abstract

Copolymers of N-isopropylacrylamide (NIPAAm), 2-hydroxyethyl methacryl lactate (HEMAlactate) and acrylic acid (AAc) were prepared, with varying mole ratios of monomers, to develop a bioresorbable in-situ-gelling material with a time-dependent lower critical solution temperature (LCST). The synthesized copolymers were characterized by nuclear magnetic resonance, gel permeation chromatography and differential scanning calorimetry. In 0.1 M phosphate-buffered saline solution of pH 7.4, these copolymers had an LCST below body temperature. The LCST decreased as the HEMAlactate content of the copolymers was increased. Furthermore, in these conditions, the LCST of the copolymers exhibited time-dependent properties, due to hydrolysis of the HEMA-lactate. As the HEMAlactate hydrolyzed, the copolymers became more hydrophilic, thereby leading to an increase in LCST. This hydrophilicity caused copolymers of approximately 6 mol% of AAc to exhibit an LCST above body temperature after hydrolysis. In neutral solution, copolymers with varying mol% of AAc saw their LCST rise above 37 • C within one to ten days, depending upon the HEMA-lactate/NIPAAm ratio, due to the complete hydrolysis of the HEMA-lactate. The above properties indicate that these copolymers would be useful for drug delivery because their variable LCST makes them bioresorbable.

New Hydrolysis-Dependent Thermosensitive Polymer for an Injectable Degradable System

“…In poly(NIPAAm-co-Hydroxyethyl methacrylate [HEMA]-lactate), an increase in the HEMA-lactate monomer increases the time of degradation. 11 In that case, the degradation product, HEMA, left on the polymer chain does not produce a charge on the polymer and does not significantly affect the hydrophilicity.…”

“…reported the synthesis of a new type of thermosensitive NIPAAm copolymer with hydrolysable lactate ester side groups and the LCST increases after the hydrolysis of the ester groups. 11,[14][15][16][17] In this system, a low molecular weight by-product of the degradation is lactic acid. Synthesis of NIPAAm with cyclic monomer, 2-methylene-1,3-dioxepane (MDO), and its biodegradable properties have been described by Sun, et.…”

In Situ‐Gelling, Erodible N‐Isopropylacrylamide Copolymers

“…[5] In brief, the total monomer concentration was 0.1 g·mL −1 in 1, 4-dioxane (10 wt.-%). AIBN was used as an initiator (initiator/total amount of monomers = 7 × 10 −3 mol/mol).…”

“…[5][6] The degree of polymerization (DP) of the lactate graft in HEMA-lactate was calculated from the ratio of the integrals of 1-ethylene and methine peaks at 5.6 and 5.1-5.3 ppm, respectively. The average degree of polymerization of lactate obtained was 2.3 and 2.5.…”

“…In our previous report, by introducing acrylic acid into copolymers of NIPAAm and HEMA-lactate, copolymers with an LCST above 37 o C after hydrolysis were synthesized and characterized. [5] Now we study the detailed characterization and gelation properties of these polymers for in situ-forming, injectable, and bioerodible carriers.…”