Wing-Fu Lai

Nucleic acid delivery with chitosan and its derivatives

Chitosan is a naturally occurring cationic mucopolysaccharide. It is generally biocompatible, biodegradable, mucoadhesive, non-immunogenic and non-toxic. Although chitosan is able to condense nucleic acids (NA) (both DNA and RNA) and protect them from nuclease degradation, its poor water solubility and low transfection efficacy have impeded its use as an NA carrier. In order to overcome such limitations, a multitude of strategies for chitosan modification and formulation have been proposed. In this article, we will first give a brief overview of the physical and biological properties of chitosan. Then, with a special focus on plasmid DNA delivery, we will have a detailed discussion of the latest advances in chitosan-mediated NA transfer. For future research, the following three important areas will be discussed: chitosan-mediated therapeutic small RNA transfer, structure-activity relationships (SAR) in chitosan vector design, and chitosan-mediated oral/nasal NA therapy.

Cyclodextrins in non-viral gene delivery.

Abstract Cyclodextrins (CDs) are naturally occurring cyclic oligosaccharides. They consist of (α-1,4)-linked glucose units, and possess a basket-shaped topology with an “inner–outer” amphiphilic character. Over the years, substantial efforts have been undertaken to investigate the possible use of CDs in drug delivery and controlled drug release, yet the potential of CDs in gene delivery has received comparatively less discussion in the literature. In this article, we will first discuss the properties of CDs for gene delivery, followed by a synopsis of the use of CDs in development and modification of non-viral gene carriers. Finally, areas that are noteworthy in CD-based gene delivery will be highlighted for future research. Due to the application prospects of CDs, it is anticipated that CDs will continue to emerge as an important tool for vector development, and will play significant roles in facilitating non-viral gene delivery in the forthcoming decades.

In vivo nucleic acid delivery with PEI and its derivatives: current status and perspectives

Poly(ethylenimine) (PEI) has recently emerged as a favorable candidate for nucleic acid (NA) delivery because of its good effectivity at low cost. Despite copious derivatives and formulations being explored over the years, there is a scarcity of efforts to systematically review the current status and unmet needs of related research. The objective of this article is to fill this gap by revisiting the recent advances and challenges in in vivo NA delivery mediated by PEI. For this, related literature was retrieved from PubMed and Web of Science, and among the 530 articles yielded, 49 recent in vivo studies were selected for further analysis. Based on the distillation of literature, implications for research will be drawn and prospects of PEI-mediated NA delivery for stem cell- and RNA-based therapies will be explored. It is hoped that this article could add a new insight to the field and to clinical endeavors in the future.

Revisiting the melamine contamination event in China: implications for ethics in food technology.

Food technology is a burgeoning field of applied science, invading many areas of the food industry and making contributions to economic advancement; however, little research has focused on ethical aspects in this field. This article attempts to fill this knowledge gap by revisiting the tainted milk event in China in 2008, followed by a detailed discussion of the application of food technology ethics in industrial contexts. Through the lesson learnt in the Chinese food industry, it is hoped that more global concerns on ethical issues in food technology will be raised, thereby creating a more humane food production industry.

Multicompartment Microgel Beads for Co-Delivery of Multiple Drugs at Individual Release Rates

Multidrug therapy may yield higher therapeutic effects as compared to monotherapy, yet its wide application has been hampered by the limitations of conventional drug delivery systems, in which not only incompatible drugs cannot be co-delivered but also the release rates of individual co-delivered drugs cannot be tuned separately. Regarding these limitations, we adopt the microfluidic electrospray technology to fabricate alginate-based multicompartment microgel beads. By using cadmium-telluride (CdTe) quantum dots (QDs) and a quenching agent as a model pair, the beads are shown to effectively separate incompatible drugs during co-delivery, and significantly prolong the time of observable fluorescence emission from QDs co-delivered with a quenching agent. Moreover, the drug release rates from different compartments can be tuned using the polymer blending technique to achieve a variety of drug release patterns. This study is one of the first to adopt the microfluidic electrospray technology to generate microgel beads with such versatility for co-delivery of multiple drugs. Our results provide evidence for the promising potential of our beads to be further developed as a carrier for multidrug therapy and other applications that require co-administration of multiple bioactive agents.

Hypromellose-graft-chitosan and Its Polyelectrolyte Complex as Novel Systems for Sustained Drug Delivery

Polyelectrolyte complexes formed between chitosan (CS) and anionic polymers have attracted increasing interest in drug delivery. In this study, CS is copolymerized with hypromellose via a coupling reagent-mediated approach to form a water-soluble, nontoxic CS derivative, namely hypromellose-graft-CS (HC), which is subsequently complexed with carboxymethylcellulose (CMC) to generate a polyampholytic hydrogel. When compared with conventional CS, HC is highly water-soluble across a wide pH range, and has a substantially higher pH buffering capacity to provide a pH-stable environment for delivery of drugs. In addition, the polyelectrolyte complex of HC exhibits a drug encapsulation efficiency of over 90% in all drugs tested, which is 1-2 fold higher than the efficiency attainable by the polyelectrolyte complex of conventional CS, with a 2-3 fold longer duration of sustained drug release. Our results indicate that as a novel polymer, HC has excellent promise for future pharmaceutical applications.

Evolving Marine Biomimetics for Regenerative Dentistry

New products that help make human tissue and organ regeneration more effective are in high demand and include materials, structures and substrates that drive cell-to-tissue transformations, orchestrate anatomical assembly and tissue integration with biology. Marine organisms are exemplary bioresources that have extensive possibilities in supporting and facilitating development of human tissue substitutes. Such organisms represent a deep and diverse reserve of materials, substrates and structures that can facilitate tissue reconstruction within lab-based cultures. The reason is that they possess sophisticated structures, architectures and biomaterial designs that are still difficult to replicate using synthetic processes, so far. These products offer tantalizing pre-made options that are versatile, adaptable and have many functions for current tissue engineers seeking fresh solutions to the deficiencies in existing dental biomaterials, which lack the intrinsic elements of biofunctioning, structural and mechanical design to regenerate anatomically correct dental tissues both in the culture dish and in vivo.

Design and fabrication of hydrogel-based nanoparticulate systems for in vivo drug delivery.

Hydrogels are swellable polymer networks which can imbibe a substantial amount of fluids. Compared to bulk hydrogels, hydrogel nanoparticles exhibit added values in drug delivery because they can be internalized into cells to deliver pharmaceutical agents into the cytosol. Their large surface area also allows for multivalent conjugations, making optimization of the nanoparticles towards in vivo and clinical applications possible. These features, together with the tunable properties and biocompatibility of hydrogels, account for the widespread use of hydrogel-based nanoparticulate systems in drug formulation. From an in vivo perspective, this article presents the latest advances in fabrication and engineering of hydrogel nanoparticles, and illuminates future avenues to enhance the potential of hydrogel-based nanoparticulate systems in treatment development and drug administration.

Beyond Sole Longevity: A Social Perspective on Healthspan Extension

Pursuance of longevity is not only combating decrepitude but it is also extending the health span; otherwise longevity would result in a universal medical and social burden. As revealed by the literature, the attainment of a healthy life could be impacted by the social milieu. An inquiry of this kind could hardly be settled by mere laboratory endeavors, and thus serious discussion of the social dimension of life span extension is imperative. However, little attention has been paid to this need in the biogerontological field. In view of this gap, the aim of this article is to explore the health relationship of the social milieu by using social relations as an example and to raise the awareness within our biogerontological community of the relevance of the social milieu to our existing efforts on longevity pursuance. It is hoped that through this article and with the success of antiaging therapies, not only could collaborative work between biogerontologists and scholars in other disciplines be stimulated, but indefinite extension of both life span and health span could also be achieved in the future.

Molecular and engineering approaches to regenerate and repair teeth in mammals

Continuous replacement of teeth throughout the lifespan of an individual is possibly basal for most of the vertebrates including fish and reptiles; however, mammals generally have a limited capacity of tooth renewal. The ability to induce cellular differentiation in adults to replace lost or damaged cells in mammals, or to tissue-engineer organs in vitro, has hence become one of the major goals of regenerative medicine. In this article, we will revisit some of the important signals and tissue interactions that regulate mammalian tooth development, and will offer a synopsis of the latest progress in tooth regeneration and repair via molecular and engineering approaches. It is hoped that this article will not only offer an overview of recent technologies in tooth regeneration and repair but will also stimulate more interdisciplinary research in this field to turn the pursuit of tooth regeneration and repair into practical reality.