Review of Applications and Future Prospects of Stimuli-Responsive Hydrogel Based on Thermo-Responsive Biopolymers in Drug Delivery Systems

Abstract

Some of thermo-responsive polysaccharides, namely, cellulose, xyloglucan, and chitosan, and protein-like gelatin or elastin-like polypeptides can exhibit temperature dependent sol-gel transitions. Due to their biodegradability, biocompatibility, and non-toxicity, such biomaterials are becoming popular for drug delivery and tissue engineering applications. This paper aims to review the properties of sol-gel transition, mechanical strength, drug release (bioavailability of drugs), and cytotoxicity of stimuli-responsive hydrogel made of thermo-responsive biopolymers in drug delivery systems. One of the major applications of such thermos-responsive biopolymers is on textile-based transdermal therapy where the formulation, mechanical, and drug release properties and the cytotoxicity of thermo-responsive hydrogel in drug delivery systems of traditional Chinese medicine have been fully reviewed. Textile-based transdermal therapy, a non-invasive method to treat skin-related disease, can overcome the poor bioavailability of drugs from conventional non-invasive administration. This study also discusses the future prospects of stimuli-responsive hydrogels made of thermo-responsive biopolymers for non-invasive treatment of skin-related disease via textile-based transdermal therapy.

Keywords: LCST; biopolymer; drug delivery; polysaccharide; thermo-responsive hydrogel; transdermal therapy.

Figure 1

The sol–gel transition of LCST-type thermo-responsive polymer-based drug delivery system (Schematic presentation). Formulation over LCST changes to hydrogel from the solution state. LCST-type thermo-responsive polymer in solution forms micelles at low concentration and that further aggregates at high polymer concentration to form gel at a temperature (≥LCST).

Figure 2

LCST-type formulation undergoes sol–gel transition with increase in temperature while UCST-type formulation undergoes sol–gel transition as the temperature decreases. The black colored curved lines indicate the boundary of phase separation.

Figure 3

The formation of drug-loaded biopolymer-based thermo-responsive hydrogel system via in situ gel formation and its bio-medical applications including cancer treatment, transdermal, and bone regeneration (Flow-chart presentation).

Figure 4

The chemical structures of thermo-responsive polysaccharides: (A) methylcellulose (water-soluble derivative of cellulose); (B) chitosan; and (C) xyloglucan. The chemical structures of the compounds are drawn using ChemDraw Prime software.

Figure 5

(A) UCST-type sol–gel transition of drug-loaded hydrogel system of gelatin; and (B) LCST-type sol–gel transition of drug-loaded hydrogel system of physically blended gelatin and other biopolymer (Schematic presentation).

Figure 6

(A) The consensus the repeat sequence of elastin-like polypeptide (XAA: any amino acid except proline); and (B) Sol–gel transformation of elastin-like polypeptide with an increase in temperature. The single molecule of the elastin-like polypeptide is made of hydrophilic and hydrophobic blocks and starts to form aggregates upon heating through micellar intermediate formation. Above inverse transition temperature of both hydrophobic and hydrophilic blocks, elastin-like polypeptides start to form aggregates. In addition, upon cooling below their inverse transition temperature, the aggregate changes to single molecules in the solution.