Fabrication of thermal sensitive folic acid based supramolecular hybrid gels for injectable drug release gels

• An improved mechanical supramolecular hybrid gel based on folic acid
• The hybrid gel is thermal sensitive and the gelation temperature can be adjusted under external stimuli.
• The hybrid gel can be used as an injectable gel for drug delivery.

Thermal sensitive supramolecular hybrid gels for injectable drug release were prepared by adding different amounts of agar into folic acid (FA) gelator. The gelation temperature was modulated in order to form injectable gel with body temperature (37 °C). Such kind of folic acid-agar (FAG) hybrid gel makes it possible to use supramolecular gel as injectable drug loaded gels for drug release. FT-IR and UV–vis spectra indicate that agar macromolecules involve in the self-assembly process through intermolecular H-bonding and π-π stacking interactions with FA molecules. The SEM and TEM images demonstrate that the fiber diameter of FAG hybrid gel is about 20 nm, much smaller than that of FA gel (40 nm). However, FAG hybrid has a denser nano-fibrous network structure than FA gels. Moreover, FAG hybrid gel is endowed with a more ordered network structure and a little better crystallization capability by adding agar. FAG hybrid gel also shows a shear-thinning behavior but the shear viscosity is about 2 times higher than that of FA gel. Compared with FA gel, the storage (G′) and loss (G″) moduli of the FAG gel are higher, which implies an enhanced gel strength. At the same time, both FA and FAG gels are facilely affected by some external factors such as acid, base and salts. In acidic or basic conditions, the strength became weak and the gelation temperature (Tg) decreased. While, within certain concentrations, the salt (NaCl) increased the gel strength and Tg. FAG gel suffered lower mass loss and owned better stability in different pH solutions compared with pure FA gel. The release behavior of the FA and injectable FAG gels was investigated by using Rhodamine B as a mimic model drug. FAG hybrid gel shows a long release profile and the release time is 3 times longer than that of FA gel, up to 30 h, and the accumulative release amount reaches about 86%. So it is a potential injectable gel for sustained release drug delivery system.