Dual (pH and thermal) stimuli-responsive Pickering emulsion stabilized by chitosan-carrageenan composite microgels.

Formulation of water-in-oil (W/O) Pickering emulsion (PE) for food applications has been largely restricted by the limited choices of food-grade Pickering emulsifiers. In this study, composite microgels made of chitosan and carrageenan were explored as a dual (pH and thermal) stimuli-responsive Pickering emulsifier for the stabilization of W/O PE. The chitosan-carrageenan (CS-CRG) composite microgels not only exhibited pH- and thermo-responsiveness, but also displayed enhanced lipophilicity as compared to the discrete polymers. The stability of the CS-CRG-stabilized W/O PE system (CS-CRG PE) was governed by CS:CRG mass ratio and oil fractions used. The CS-CRG PE remained stable at acidic pH and at temperatures below 40 °C. The instability of CS-CRG composite microgels at alkaline pH and at temperatures above 40 °C rendered the demulsification of CS-CRG PE. This stimuli-responsive W/O PE could unlock new opportunities for the development of stimuli-responsive W/O PE using food-grade materials.

Stimuli-responsive nanoassemblies for targeted delivery against tumor and its microenvironment.

Despite the emergence of various cancer treatments, such as surgery, chemotherapy, radiotherapy, and immunotherapy, their use remains restricted owing to their limited tumor elimination efficacy and side effects. The use of nanoassemblies as delivery systems in nanomedicine for tumor diagnosis and therapy is flourishing. These nanoassemblies can be designed to have various shapes, sizes, and surface charges to meet the requirements of different applications. It is crucial for nanoassemblies to have enhanced delivery of payloads while inducing minimal to no toxicity to healthy tissues. In this review, stimuli-responsive nanoassemblies capable of combating the tumor microenvironment (TME) are discussed. First, various TME characteristics, such as hypoxia, oxidoreduction, adenosine triphosphate (ATP) elevation, and acidic TME, are described. Subsequently, the unique characteristics of the vascular and stromal TME are differentiated, and multiple barriers that have to be overcome are discussed. Furthermore, strategies to overcome these barriers for successful drug delivery to the targeted site are reviewed and summarized. In conclusion, the possible challenges and prospects of using these nanoassemblies for tumor-targeted delivery are discussed. This review aims at inspiring researchers to develop stimuli-responsive nanoassemblies for tumor-targeted delivery for clinical applications.

Stimuli-controllable iron oxide nanoparticle assemblies: Design, manipulation and bio-applications.

Despite its wide establishment over the years, iron oxide nanoparticle (IONP) still draws extensive interest in the biomedical fields due to its biocompatibility, biodegradability, magnetivity and surface tunable properties. IONP has been used for the MRI, magnetic targeting, drug delivery and hyperthermia of various diseases. However, their poor stability, low diagnostic sensitivity and low disease-specificity have resulted in unsatisfying diagnostic and therapeutic outputs. The surface functionalization of IONP with biocompatible and colloidally stable components appears to be promising to improve its circulation and colloidal stability. Importantly, through surface functionalization with designated functional components, IONP-based assemblies with multiple stimuli-responsivity could be formed to achieve an accurate and efficient delivery of IONP to disease sites for an improved disease diagnosis and therapy. In this work, we first described the design of biocompatible and stable IONP assemblies. Further, their stimuli-driven manipulation strategies are reviewed. Next, the utilization of IONP assemblies for disease diagnosis, therapy and imaging-guided therapy are discussed. Then, the potential toxicity of IONPs and their clinical usages are described. Finally, the intrinsic challenges and future outlooks of IONP assemblies are commented. This review provides recent insights into IONP assemblies, which could inspire researchers on the future development of multi-responsive and disease-targetable nanoassemblies for biomedical utilization.

Spray-dried alginate-coated Pickering emulsion stabilized by chitosan for improved oxidative stability and in vitro release profile.

The commercial application of liquid-state Pickering emulsions in food systems remains a major challenge. In this study, we developed a spray-dried Pickering emulsion powder using chitosan as a Pickering emulsifier and alginate as a coating material. The functionality of the powder was evaluated in terms of its oxidative stability, pH-responsiveness, mucoadhesivity, and lipid digestibility. The Pickering emulsion powder was oxidatively more stable than the conventional emulsion powder stabilized by gum Arabic. The powder exhibited pH-responsiveness, whereby it remained intact in acidic pH, but dissolved to release the emulsion in 'Pickering form' at near-neutral pH. The Pickering emulsion powder was also mucoadhesive and could be digested by lipase in a controlled manner. These findings suggested that the multi-functional Pickering emulsion powder could be a potential delivery system for applications in the food industry.

Particle designs for the stabilization and controlled-delivery of protein drugs by biopolymers: a case study on insulin.

Natural biopolymers have attracted considerable interest for the development of delivery systems for protein drugs owing to their biocompatibility, non-toxicity, renewability and mild processing conditions. This paper offers an overview of the current status and future perspectives of particle designs using biopolymers for the stabilization and controlled-delivery of a model protein drug--insulin. We first describe the design criteria for polymeric encapsulation and subsequently classify the basic principles of particle fabrication as well as the existing particle designs for oral insulin encapsulation. The performances of these existing particle designs in terms of insulin stability and in vitro release behavior in acidic and alkaline media, as well as their in vivo performance are compared and reviewed. This review forms the basis for future works on the optimization of particle design and material formulation for the development of an improved oral delivery system for protein drugs.

Sclerostin stimulates osteocyte support of osteoclast activity by a RANKL-dependent pathway.

Sclerostin is a product of mature osteocytes embedded in mineralised bone and is a negative regulator of bone mass and osteoblast differentiation. While evidence suggests that sclerostin has an anti-anabolic role, the possibility also exists that sclerostin has catabolic activity. To test this we treated human primary pre-osteocyte cultures, cells we have found are exquisitely sensitive to sclerostin, or mouse osteocyte-like MLO-Y4 cells, with recombinant human sclerostin (rhSCL) and measured effects on pro-catabolic gene expression. Sclerostin dose-dependently up-regulated the expression of receptor activator of nuclear factor kappa B (RANKL) mRNA and down-regulated that of osteoprotegerin (OPG) mRNA, causing an increase in the RANK:OPG mRNA ratio. To examine the effects of rhSCL on resulting osteoclastic activity, MLO-Y4 cells plated onto a bone-like substrate were primed with rhSCL for 3 days and then either mouse splenocytes or human peripheral blood mononuclear cells (PBMC) were added. This resulted in cultures with elevated osteoclastic resorption (approximately 7-fold) compared to untreated co-cultures. The increased resorption was abolished by co-addition of recombinant OPG. In co-cultures of MLO-Y4 cells with PBMC, SCL also increased the number and size of the TRAP-positive multinucleated cells formed. Importantly, rhSCL had no effect on TRAP-positive cell formation from monocultures of either splenocytes or PBMC. Further, rhSCL did not induce apoptosis of MLO-Y4 cells, as determined by caspase activity assays, demonstrating that the osteoclastic response was not driven by dying osteocytes. Together, these results suggest that sclerostin may have a catabolic action through promotion of osteoclast formation and activity by osteocytes, in a RANKL-dependent manner.