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Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used in treating type 2 diabetes (T2D). However, owing to their limited oral bioavailability, most commercially available GLP-1 RAs are administered through frequent subcutaneous injections, which may result in poor patient compliance during clinical treatment. To improve patients' compliance, sustained-release GLP-1 RA-loaded microspheres have been explored. This review is an overview of recent progress and research in GLP-1 RA-loaded microspheres. First, the fabrication methods of GLP-1 RA-loaded microspheres including the coacervation method, emulsion–solvent evaporation method based on agitation, premix membrane emulsification technology, spray drying, microfluidic droplet technology, and supercritical fluid technology are summarized. Next, the strategies for maintaining GLP-1 RAs' stability and activity in microspheres by adding additives and PEGylation are reviewed. Finally, the effect of particle size, drug distribution, the internal structure of microspheres, and the hydrogel/microsphere composite strategy on improved release behavior is summarized. [ABSTRACT FROM AUTHOR]

Chemotherapy has been widely used in clinical practice for cancer treatment. A major challenge for a successful chemotherapy is to potentiate the anticancer activity, whilst reducing the severe side effects. In this context, we design a bio-inspired protein–gold nanoconstruct (denoted as AFt–Au hereafter) with a core–void–shell structure which exhibits a high selectivity towards carcinoma cells. Anticancer drug 5-fluorouracil (5-FU) can be sequestered into the void space of the construct to produce an integrated nanoscale hybrid AFt–AuFU that exhibits an increased cellular uptake of 5-FU. More importantly, AFt–Au, serving as a bio-nano-chemosensitizer, renders carcinoma cells more susceptible to 5-FU by cell-cycle regulation, and thus, leads to a dramatic decrease of the IC50 value (i.e. the drug concentration required to kill 50% of the cell population) of 5-FU in HepG2 cells from 138.3 μM to 9.2 μM. Besides HepG2 cells, a remarkably enhanced anticancer efficacy and potentially reduced side effects are also achieved in other cell lines. Our further work reveals that the drug 5-FU is internalized into cells with AFt–Au primarily via receptor-mediated endocytosis (RME). After internalization, AFt–AuFU colocalizes with lysosomes which trigger the release of 5-FU under acidic conditions. Overall, our approach provides a novel procedure in nanoscience that promises an optimal chemotherapeutic outcome. [ABSTRACT FROM AUTHOR]

Pickering emulsions stabilized by solid particles have been widely studied in the past decades due to improved stability and reduced use of small molecular surfactants. Recently, the application of Pickering emulsions in pharmaceutics has been attracting increasing attention but very limited practical use has been demonstrated, because most of the investigated particles possess poor biodegradability, which is inappropriate in pharmaceutics. Some reported biodegradable particles were too hydrophilic to stabilize emulsions, which needs further particle modification or additional surfactants. Fortunately, biodegradable poly(d,l-lactic-co-glycolic acid) (PLGA) with tunable hydrophilicity makes itself a promising material to prepare Pickering emulsions. However, the mechanism of emulsion stabilization still remains unknown. Moreover, fabrication of large amounts of uniform-sized and size-controlled PLGA particles by traditional methods is very difficult, which further increases the difficulty to perform the research. In the present study, we applied Shirasu Porous Glass (SPG) premix membrane emulsification to solve this problem. The stabilization mechanism of Pickering emulsions stabilized by PLGA particles was systematically studied for the first time. The factors including oil type, particle properties, concentration, molecular weight (M w ) and oil-water volume ratio were analyzed through particle wettability and interfacial influence. We found that octanol was an appropriate oil type, and its small particle size, high particle concentration and high M w were favorable for emulsion stability. By changing the oil-water volume ratio, stable emulsions were also readily achieved. These studies proved that Pickering emulsions stabilized by PLGA particles had wide potential applications in pharmaceutics and tissue engineering.

Colloidosomes are microcapsules that consist of a hollow core coated by a shell composed of self-assembled colloidal particles. In recent years, they have attracted significant attention as potential vehicles for the controlled delivery of active ingredients. A key challenge in such applications is the production of uniform-sized colloidosomes for the encapsulation of active ingredients such that the actual delivery amount can be well controlled. Based on our previous study on an ethyl acetate-in-water emulsion stabilized by chitosan-coated alginate particles, we further prepared monodisperse colloidosomes with a high yield and low permeability by combining the premix membrane emulsification technique and polymer deposition method. The potential application of the formed colloidosomes as oral insulin delivery vehicles was investigated. Our results revealed that in comparison to conventional PLGA microspheres, the formulated colloidosomes showed high drug encapsulation efficiency (up to 96.7%) and an obvious pH sensitive release profile. Moreover, in animal testing, the colloidosomes formulation achieved a long-term hypoglycemic effect up to 6 h, which confirmed its application as an oral drug delivery system.

Highly efficient immobilization of multi-enzyme systems involving cofactor regeneration represents one of the greatest challenges in bioprocessing. Particulate artificial cells with enzymes and cofactors encapsulated within microcapsules have long been the major type of multi-enzyme biocatalysts. In the present work, a novel hollow nanofiber-based artificial cell that performs multi-step reactions involving efficient coenzyme regeneration was fabricated in situ by a facile co-axial electrospinning process. To that end, a mixture of glycerol and water containing the dissolved multi-enzyme system for the bile acid assay, which included 3α-hydroxysteroid dehydrogenase (3α-HSD), diaphorase (DP) and NADH was fed as the core phase solution, and a N,N-dimethylacetylamide solution of 30 wt% polyurethane was fed as the shell phase solution during the co-axial electrospinning. The relationship between the structures of the hollow nanofibers and the activity and stability of the encapsulated enzymes was studied. At core and shell phase electrospinning solution flow rates of 0.07 and 0.5 mL h -1 , activity recoveries as high as 76% and 82% were obtained for the encapsulated 3α-HSD and DP. The hollow nanofiber-based artificial cells were successfully used for the bile acid assay, yielding good linearity for bile acid concentrations ranging from 0-200 μM. Compared with the solution-based multi-enzyme system, the hollow nanofiber-based multi-enzyme system presented a lumped activity recovery of 75%. In addition, the hollow nanofiber provided the multi-enzyme system confined inside the nano-domain of the hollow fibers with a unique stabilizing mechanism, such that more than a 170-fold increase in half-life at 25 °C was obtained for the encapsulated 3α-HSD and DP. This study is expected to greatly promote and broaden the application of multi-enzyme systems in industry, biosensor, biomedical, and many other related research fields.