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

Abstract

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 20nm, much smaller than that of FA gel (40nm). 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 30h, and the accumulative release amount reaches about 86%. So it is a potential injectable gel for sustained release drug delivery system.

Bolaamphiphilic Bis-Dehydropeptide Hydrogels as Potential Drug Release Systems

“…Supramolecular hydrogels have attracted considerable attention due to their potential applications as promising biomaterials for many biotechnological and biomedical applications, such as drug delivery [1,2], cell culture [3], tissue engineering [4], wound healing [5,6], and many others. Upon receiving an external trigger, short peptides capped with aromatic groups on the N-terminus can often self-assemble into three-dimensional (3D) networks, forming fibers that can trap water molecules, providing biocompatible and biodegradable supramolecular hydrogels [7].…”

Beyond Covalent Crosslinks: Applications of Supramolecular Gels

“…The abilities of supramolecular gels to include temperature-sensitive functionality, rheological tunability, and stability when used as a platform for drug release have garnered interest in their use for injectable drug delivery applications. A thermally-sensitive folic acid-agar supramolecular hybrid gel in a 1:1 DMSO-water mixture by Song et al demonstrated mechanical tunability and a drug release profile with a low initial burst and long release time with a model drug [101]. With a specific application in mind, Dai et al developed a supramolecular gel in aqueous media based on host-guest inclusion complexation between α-cyclodextrin and anti-tumor drug-loaded micelles that exhibited several notable properties, including facile preparation, high stability, an attractive drug release profile, low toxicity, and effective in vitro and in vivo anti-tumor activity [102].…”

Bolaamphiphilic Bis-Dehydropeptide Hydrogels as Potential Drug Release Systems

“…Supramolecular hydrogels have attracted considerable attention due to their potential applications as promising biomaterials for many biotechnological and biomedical applications, such as: drug delivery, [1,2] cell culture, [3] tissue engineering, [4] wound healing [5,6] and many others. Upon receiving an external trigger, short peptides capped with aromatic groups on the Nterminus can often self-assemble into three-dimensional (3D) networks, forming fibres which can trap water molecules, providing biocompatible and biodegradable supramolecular hydrogels [7].…”