Preparation of thermo-responsive and injectable hydrogels based on hyaluronic acid and poly(N-isopropylacrylamide) and their drug release behaviors

Abstract

Copolymers composed of hyaluronic acid (HA) and poly(N-isopropylacrylamide) (PNIPAAm) were prepared to create temperature-sensitive injectable gels for use in controlled drug delivery applications. Semi-telechelic PNIPAAm, with amino groups at the end of each main chain, was synthesized by radical polymerization using 2-aminoethanethiol hydrochloride (AESH) as the chain transfer agent, and was then grafted onto the carboxyl groups of HA using carbodiimide chemistry. The result of the thermo-optical analysis revealed that the phase transition of the PNIPAAm-grafted HA solution occurred at around 30~33 o C. As the graft yield of PNIPAAm onto the HA backbone increased, the HA-g-PNIPAAm copolymer solution exhibited sharper phase transition. The short chain PNIPAAm-grafted HA (M w = 6,100) showed a narrower temperature range for optical turbidity changes than the long chain PNIPAAm-grafted HA (M w = 13,100). PNIPAAm-grafted HA exhibited an increase in viscosity above 35 o C, thus allowing the gels to maintain their shape for 24 h after in vivo administration. From the in vitro riboflavin release study, the HA-g-PNIPAAm gel showed a more sustained release behavior when the grafting yield of PNIPAAm onto the HA backbone was increased. In addition, BSA released from the PNIPAAm-g-HA gels showed a maximum concentration in the blood 12 h after being injected into the dorsal surface of a rabbit, followed by a sustained release profile after 60 h.

Bioengineering the Skin–Implant Interface: The Use of Regenerative Therapies in Implanted Devices

“…64,128 It would even be possible to use thermo-responsive and injectable HA hydrogels. 49 The only caveat on the use of HA is to avoid gross and abnormal accumulation of HA in the tissues, requiring that concentrations should be kept sufficiently low. 61…”

Photo-crosslinking hyaluronan-heparin hybrid hydrogels for BMP-2 sustained delivery

“…Here, BMP-2 was used as the model GF for loading and delivery. The in site encapsulation of macromolecules such as GFs and proteins are generally adopted during the gelation in consideration of the difficulty of macromolecules entering a swollen gel [29,30]. However, this method was not used in this work because UV radiation was at the risk of denaturing BMP-2.…”

Photocrosslinkable Polymers for Biomedical Applications

“…Another approach on the synthesis of crosslinkable hydrogels is grafting of PNIPAAm linear chains onto natural polymers (Hoare and Kohane, 2008). As an example, temperature-sensitive injectable gels were prepared by grafting amino-terminated semitelechelic PNIPAAm onto hyaluronic acid (HA) backbones (Ha et al, 2006). Riboflavin was entrapped in the resulting gel and in vitro tests results showed a more sustained release behavior when the grafting yield of PNIPAAm onto the HA backbone was increased.…”