Photoacoustic Drug Delivery

Photoacoustic (PA) technology holds great potential in clinical translation as a new non-invasive bioimaging modality. In contrast to conventional optical imaging, PA imaging (PAI) enables higher resolution imaging with deeper imaging depth. Besides applications for diagnosis, PA has also been extended to theranostic applications. The guidance of PAI facilitates remotely controlled drug delivery. This review focuses on the recent development of PAI-mediated drug delivery systems. We provide an overview of the design of different PAI agents for drug delivery. The challenges and further opportunities regarding PA therapy are also discussed

Primum non nocere: Refocusing our attention on severe hypoglycemia prevention

Severe hypoglycemia, defined as low blood glucose requiring assistance for recovery, is arguably the most dangerous complication of type 1 diabetes as it can result in permanent cognitive impairment, seizure, coma, accidents, and death. Since the Diabetes Control and Complications Trial (DCCT) demonstrated that intensive intervention to normalize glucose prevents long-term complications but at the price of a threefold increase in the rate of severe hypoglycemia, hypoglycemia has been recognized as the major limitation to achieving tight glycemic control. Severe hypoglycemia remains prevalent among adults with type 1 diabetes, ranging from ∼1.4% per year in the DCCT/EDIC (Epidemiology of Diabetes Interventions and Complications) follow-up cohort to ∼8% in the T1D Exchange clinic registr

H2O2-Responsive Vesicles Integrated with Transcutaneous Patches for Glucose-Mediated Insulin Delivery

A self-regulated "smart" insulin administration system would be highly desirable for diabetes management. Here, a glucose-responsive insulin delivery device, which integrates H2O2-responsive polymeric vesicles (PVs) with a transcutaneous microneedle-array patch was prepared to achieve a fast response, excellent biocompatibility, and painless administration. The PVs are self-assembled from block copolymer incorporated with polyethylene glycol (PEG) and phenylboronic ester (PBE)-conjugated polyserine (designated mPEG-b-P(Ser-PBE)) and loaded with glucose oxidase (GOx) and insulin. The polymeric vesicles function as both moieties of the glucose sensing element (GOx) and the insulin release actuator to provide basal insulin release as well as promote insulin release in response to hyperglycemic states. In the current study, insulin release responds quickly to elevated glucose and its kinetics can be modulated by adjusting the concentration of GOx loaded into the microneedles. In vivo testing indicates that a single patch can regulate glucose levels effectively with reduced risk of hypoglycemia

Treatment effect heterogeneity following type 2 diabetes treatment with GLP1-receptor agonists and SGLT2-inhibitors:a systematic review

Background: A precision medicine approach in type 2 diabetes requires the identification of clinical and biological features that are reproducibly associated with differences in clinical outcomes with specific anti-hyperglycaemic therapies. Robust evidence of such treatment effect heterogeneity could support more individualized clinical decisions on optimal type 2 diabetes therapy.Methods: We performed a pre-registered systematic review of meta-analysis studies, randomized control trials, and observational studies evaluating clinical and biological features associated with heterogenous treatment effects for SGLT2-inhibitor and GLP1-receptor agonist therapies, considering glycaemic, cardiovascular, and renal outcomes. After screening 5,686 studies, we included 101 studies of SGLT2-inhibitors and 75 studies of GLP1-receptor agonists in the final systematic review.Results: Here we show that the majority of included papers have methodological limitations precluding robust assessment of treatment effect heterogeneity. For SGLT2-inhibitors, multiple observational studies suggest lower renal function as a predictor of lesser glycaemic response, while markers of reduced insulin secretion predict lesser glycaemic response with GLP1-receptor agonists. For both therapies, multiple post-hoc analyses of randomized control trials (including trial meta-analysis) identify minimal clinically relevant treatment effect heterogeneity for cardiovascular and renal outcomes.Conclusions: Current evidence on treatment effect heterogeneity for SGLT2-inhibitor and GLP1-receptor agonist therapies is limited, likely reflecting the methodological limitations of published studies. Robust and appropriately powered studies are required to understand type 2 diabetes treatment effect heterogeneity and evaluate the potential for precision medicine to inform future clinical care.</p

Synthetic beta cells for fusion-mediated dynamic insulin secretion

Generating artificial pancreatic beta cells by using synthetic materials to mimic glucose-responsive insulin secretion in a robust manner holds promise for improving clinical outcomes in people with diabetes. Here, we describe the construction of artificial beta cells (AβCs) with a multicompartmental 'vesicles-in-vesicle' superstructure equipped with a glucose-metabolism system and membrane-fusion machinery. Through a sequential cascade of glucose uptake, enzymatic oxidation and proton efflux, the AβCs can effectively distinguish between high and normal glucose levels. Under hyperglycemic conditions, high glucose uptake and oxidation generate a low pH (<5.6), which then induces steric deshielding of peptides tethered to the insulin-loaded inner small liposomal vesicles. The peptides on the small vesicles then form coiled coils with the complementary peptides anchored on the inner surfaces of large vesicles, thus bringing the membranes of the inner and outer vesicles together and triggering their fusion and insulin 'exocytosis'