Xian Jun Loh

Cyclodextrin-based supramolecular architectures: Syntheses, structures, and applications for drug and gene delivery

The supramolecular structures formed between cyclodextrins (CDs) and polymers have inspired interesting developments of novel supramolecular biomaterials. This review will update the recent progress in studies on supramolecular structures based on CDs and block copolymers, followed by the design and synthesis of CD-based supramolecular hydrogels and biodegradable polyrotaxanes for potential controlled drug delivery, and CD-containing cationic polymers and cationic polyrotaxanes for gene delivery. Supramolecular hydrogels based on the self-assembly of the inclusion complexes between CDs with biodegradable block copolymers could be used as promising injectable drug delivery systems for sustained controlled release of macromolecular drugs. Biodegradable polyrotaxanes with drug-conjugated CDs threaded on a polymer chain with degradable end-caps could be interesting supramolecular prodrugs for controlled and targeting delivery of drugs. CD-containing cationic polymers as gene carriers showed reduced cytotoxicity than non-CD-containing polymer counterparts. More importantly, the polyplexes of CD-containing cationic polymers with DNA could be pegylated through a supramolecular process using inclusion complexation between the CD moieties and a modified PEO. Finally, new cationic polyrotaxanes composed of multiple oligoethylenimine-grafted CDs threaded and end-capped on a block copolymer chain were designed and synthesized as a new class of polymeric gene delivery vectors, where the chain-interlocked cationic cyclic units formed an integrated supramolecular entity to function as a macromolecular gene vector. The development of the supramolecular biomaterials through inclusion complexation has opened up a new approach for designing novel drug and gene delivery systems, which may have many advantages over the systems based on the conventional polymeric materials.

Ultrahigh-Water-Content Supramolecular Hydrogels Exhibiting Multistimuli Responsiveness

Hydrogels are three-dimensional networked materials that are similar to soft biological tissues and have highly variable mechanical properties, making them increasingly important in a variety of biomedical and industrial applications. Herein we report the preparation of extremely high water content hydrogels (up to 99.7% water by weight) driven by strong host-guest complexation with cucurbit[8]uril (CB[8]). Cellulosic derivatives and commodity polymers such as poly(vinyl alcohol) were modified with strongly binding guests for CB[8] ternary complex formation (K(eq) = 10(12) M(-2)). When these polymers were mixed in the presence of CB[8], whereby the overall solid content was 90% cellulosic, a lightly colored, transparent hydrogel was formed instantaneously. The supramolecular nature of these hydrogels affords them with highly tunable mechanical properties, and the dynamics of the CB[8] ternary complex cross-links allows for rapid self-healing of the materials after damage caused by deformation. Moreover, these hydrogels display responsivity to a multitude of external stimuli, including temperature, chemical potential, and competing guests. These materials are easily processed, and the simplicity of their preparation, their availability from inexpensive renewable resources, and the tunability of their properties are distinguishing features for many important water-based applications.

Towards lignin-based functional materials in a sustainable world

In light of the incessant consumption of raw materials in the world today, the search for sustainable resources is ever pressing. Lignin, the second most naturally abundant biomass, which makes up 15% to 35% of the cell walls of terrestrial plants, has always been treated as waste and used in low-value applications such as heat and electricity generation. However, its abundance in nature could potentially solve the problem of the rapidly depleting resources if it was successfully translated into a renewable resource or valorized to higher value materials. Advanced lignin modification chemistry has generated a number of functional lignin-based polymers, which integrate both the intrinsic features of lignin and additional properties of the grafted polymers. These modified lignin and its copolymers display better miscibility with other polymeric matrices, leading to improved performance for these lignin/polymer composites. This review summarizes the progress in using such biopolymers as reinforcement fillers, antioxidants, UV adsorbents, antimicrobial agents, carbon precursors and biomaterials for tissue engineering and gene therapy. Recent developments in lignin-based smart materials are discussed as well.

Nanoparticle–Hydrogel Composites: Concept, Design, and Applications of These Promising, Multi‐Functional Materials

New technologies rely on the development of new materials, and these may simply be the innovative combination of known components. The structural combination of a polymer hydrogel network with a nanoparticle (metals, non‐metals, metal oxides, and polymeric moieties) holds the promise of providing superior functionality to the composite material with applications in diverse fields, including catalysis, electronics, bio‐sensing, drug delivery, nano‐medicine, and environmental remediation. This mixing may result in a synergistic property enhancement of each component: for example, the mechanical strength of the hydrogel and concomitantly decrease aggregation of the nanoparticles. These mutual benefits and the associated potential applications have seen a surge of interest in the past decade from multi‐disciplinary research groups. Recent advances in nanoparticle–hydrogel composites are herein reviewed with a focus on their synthesis, design, potential applications, and the inherent challenges accompanying these exciting materials.

Controlled drug release from biodegradable thermoresponsive physical hydrogel nanofibers.

Hydrogel nanofiber mats based on thermoresponsive multiblock poly(ester urethane)s comprising poly(ethylene glycol) (PEG), poly(propylene glycol) (PPG), and poly(epsilon-caprolactone) (PCL) segments were fabricated by electrospinning. The hydrogel nanofiber mats were more water absorbent under cold conditions and shrunk when exposed to higher temperatures. The rate of protein release could be controlled by changing the temperature of the nanofiber environment. Cell culture studies on the nanofiber mats were carried out using human dermal fibroblasts, and healthy cell morphology was observed. The adherent viable cells were quantified by MTS after rinsing in excess buffer solution. The results showed that these nanofiber scaffolds supported excellent cell adhesion, comparable with the pure PCL nanofibers. The increased hydrophilicity of these hydrogel nanofiber mats led to a more rapid hydrolytic degradation, compared with the pure PCL nanofiber mats. These hydrogel nanofiber scaffolds could potentially be used as thermoresponsive biodegradable supporting structures for skin tissue engineering applications.

Recent Advances of Using Hybrid Nanocarriers in Remotely Controlled Therapeutic Delivery

The development of hybrid biomaterials has been attracting great attention in the design of materials for biomedicine. The nanosized level of inorganic and organic or even bioactive components can be combined into a single material by this approach, which has created entirely new advanced compositions with truly unique properties for drug delivery. The recent advances in using hybrid nanovehicles as remotely controlled therapeutic delivery carriers are summarized with respect to different nanostructures, including hybrid host-guest nanoconjugates, micelles, nanogels, core-shell nanoparticles, liposomes, mesoporous silica, and hollow nanoconstructions. In addition, the controlled release of guest molecules from these hybrid nanovehicles in response to various remote stimuli such as alternating magnetic field, near infrared, or ultrasound triggers is further summarized to introduce the different mechanisms of remotely triggered release behavior. Through proper chemical functionalization, the hybrid nanovehicle system can be further endowed with many new properties toward specific biomedical applications.

Biodegradable polymers for electrospinning: towards biomedical applications.

Electrospinning has received much attention recently due to the growing interest in nano-technologies and the unique material properties. This review focuses on recent progress in applying electrospinning technique in production of biodegradable nanofibers to the emerging field of biomedical. It first introduces the basic theory and parameters of nanofibers fabrication, with focus on factors affecting the morphology and fiber diameter of biodegradable nanofibers. Next, commonly electrospun biodegradable nanofibers are discussed, and the comparison of the degradation rate of nanoscale materials with macroscale materials are highlighted. The article also assesses the recent advancement of biodegradable nanofibers in different biomedical applications, including tissue engineering, drug delivery, biosensor and immunoassay. Future perspectives of biodegradable nanofibers are discussed in the last section, which emphasizes on the innovation and development in electrospinning of hydrogels nanofibers, pore size control and scale-up productions.

Triply Triggered Doxorubicin Release From Supramolecular Nanocontainers

The synthesis of a supramolecular double hydrophilic block copolymer (DHBC) held together by cucurbit[8]uril (CB[8]) ternary complexation and its subsequent self-assembly into micelles is described. This system is responsive to multiple external triggers including temperature, pH and the addition of a competitive guest. The supramolecular block copolymer assembly consists of poly(N-isopropylacrylamide) (PNIPAAm) as a thermoresponsive block and poly(dimethylaminoethylmethacrylate) (PDMAEMA) as a pH-responsive block. Moreover, encapsulation and controlled drug release was demonstrated with this system using the chemotherapeutic drug doxorubicin (DOX). This triple stimuli-responsive DHBC micelle system represents an evolution over conventional double stimuli-responsive covalent diblock copolymer systems and displayed a significant reduction in the viability of HeLa cells upon triggered release of DOX from the supramolecular micellar nanocontainers.

Multi-functional fluorescent carbon dots with antibacterial and gene delivery properties†

Glucose is abundant in nature and can be found in various sources. In this study, we developed multifunctional carbon dots (CDs) with glucose and poly(ethyleneimine) (PEI), which were further quaternized using a facile approach. The CDs are designed to possess both anti-bacteria and gene delivery capabilities. The inherent property was characterized with TEM, NMR, FTIR and fluorescent spectroscopy. Antibacterial activity was evaluated with Broth minimum inhibitory concentration (MIC) assay on both Gram-positive and Gram-negative bacteria. The CDs showed excellent inhibitation to both bacteria. The expression of CDs condensed plasmid DNA in HEK 293T cells was investigated with luciferase expression assay. Gene transfection capability of the quaternized CDs was found to be up to 104 times efficient than naked DNA delivery.

Biodegradable thermogelling poly(ester urethane)s consisting of poly(lactic acid)--thermodynamics of micellization and hydrolytic degradation.

Multiblock poly(ether ester urethane)s comprising of poly(lactic acid) (PLA), poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG) segments were synthesized, and their aqueous solutions exhibited thermogelling behavior at critical gelation concentrations (CGC) ranging from 7 to 9 wt%. The chemical structures and molecular characteristics of the copolymers were studied by GPC, 1H NMR, 13C NMR and FTIR. The thermal stability of the poly(PEG/PPG/PLA urethane)s was studied by thermogravimetry analysis (TGA), and the PLA contents were calculated based on the thermal degradation profile. The results were in good agreement with those obtained from the 1H NMR measurements. The critical micellization concentration (CMC) of these water-soluble poly(ether ester urethane)s was determined at different temperatures using a dye solubilization method. The thermodynamic parameters for micelle formation were calculated, indicating that the process is largely entropy-driven. Interestingly, it appears that there exists a requirement for the system to possess a minimum gain in entropy before the thermogelling effect can be observed. Dilute copolymer solutions showed a lower critical solution temperature (LCST) behavior similar to pNIPAM dissolved in aqueous solutions. The thermogels hydrolytically degraded to polymer fragments corresponding to the constituent segment blocks within 3 months.