Research progress of self-assembled nanogel and hybrid hydrogel systems based on pullulan derivatives

Abstract

Polymer nano-sized hydrogels (nanogels) as drug delivery carriers have been investigated over the last few decades. Pullulan, a nontoxic and nonimmunogenic hydrophilic polysaccharide derived from fermentation of black yeast like Aureobasidium pullulans with great biocompatibility and biodegradability, is one of the most attractive carriers for drug delivery systems. In this review, we describe the preparation, characterization, and ‘switch-on/off’ mechanism of typical pullulan self-assembled nanogels (self-nanogels), and then introduce the development of hybrid hydrogels that are numerous resources applied for regenerative medicine. A major section is used for biomedical applications of different nanogel systems based on modified pullulan, which exert smart stimuli-responses at ambient conditions such as charge, pH, temperature, light, and redox. Pullulan self-nanogels have found increasingly extensive application in protein delivery, tissue engineering, vaccine development, cancer therapy, and biological imaging. Functional groups are incorporated into self-nanogels and contribute to expressing desirable results such as targeting and modified release. Various molecules, especially insoluble or unstable drugs and encapsulated proteins, present improved solubility and bioavailability as well as reduced side effects when incorporated into self-nanogels. Finally, the advantages and disadvantages of pullulan self-nanogels will be analyzed accordingly, and the development of pullulan nanogel systems will be reviewed.

Current and New Approaches for Mucosal Vaccine Delivery

“…Nanogel vaccine formulations can be delivered via a wide range of routes, such as parenteral, oral, nasal, pulmonary, or ocular administration [52]. Nanogels can be formulated by various polysaccharides such as chitosan, mannan, hyaluronic acid, dextrin, cycloamylose, pullulan, and enzymatically synthesized glucogen [53]. In recent years, pullulan has played a critical role in the development of nanogel systems for vaccine and drug delivery [54].…”

Micro and Nanogels for Biomedical Applications

“…Self-assembled nanogels were firstly introduced by Akiyoshi and colleagues, where hydrophilic pullulan polysaccharides were conjugated with hydrophobic cholesterol units and sonication of these amphiphilic polysaccharide derivatives in water yielded intramolecularly self-aggregated monodisperse particles with 25±5 nm sizes [22]. Moreover numerous microgels and nanogels have been reported by self-assembly process including synthetic and natural polymeric substrates such as poly(Nisopropylacrylamide) (PNIPAM) [23], poly(hydroxyethyl methacrylate) (p(HEMA)) [24], polysaccharides [25], pullulan [26], chitosan (CHI) [27][28][29][30][31][32], alginic acid [24], dextran [33,34], hyaluronic acid (HA) [35][36][37][38][39], starch derivatives [40], and polyphenols [41][42][43][44], proteins [45], polypeptides [46,47], various amino acids [48], and DNA [30,49,50] all of which were intended for biomedical applications in delivery of various therapeutic agents including small molecules, proteins, drugs, and genes and siRNAs.…”

Recent Advances in Degradable Hybrids of Biomolecules and NGs for Targeted Delivery

“…As the physical assembly generates a higher risk of adverse effects due to the low stability of the NGs in body fluids, this process, when followed by the chemical conjugation, gives a significant opportunity for the construction of highly stable, biodegradable hybrid NGs made from biopolymers. Recent investigations show that there is an opportunity for the design of the hybrid NGs in a high-throughput manner [37].…”