ABSTRACT
Subcutaneous (SC) injection is a common administration route for rapid and efficient delivery of biotherapeutics. However, syringe-based injections usually require professional assistance and are associated with pain and potential risks of infections, thus leading to undesired patient compliance and poor life quality. Herein, this work presents an ultrarapid-acting microneedle (URA-MN) patch for immediate transdermal delivery of therapeutics in a minimally invasive manner. Effervescent agents are incorporated into the tip of URA-MN for rapid generation of CO2 bubbles upon insertion into the skin, immediately powering the biotherapeutics release within a few minutes. The release kinetics of diverse agents including liraglutide (LRT), insulin, and heparin from the URA-MN patches are evaluated in three different mouse models, and the rapid release of biotherapeutics and potent therapeutic effects are achieved with only 5 min administration. Noteworthily, attributed to the short application duration and negligible residuals of MN matrix remaining in the skin, the URA-MN patch shows desirable biocompatibility after six-week administration.
Subject(s)
Drug Delivery Systems , Skin , Animals , Mice , Humans , Administration, Cutaneous , Insulin/therapeutic useABSTRACT
Microneedles have been expected for the construction of next-generation biosensors towards personalization, digitization, and intellectualization due to their metrics of minimal invasiveness, high integration, and favorable biocompatibility. Herein, an overview of state-of-the-art microneedle-based detection and sensing systems is presented. First, the designs of microneedle devices based on extraction mechanisms are concluded, corresponding to different geometries and materials of microneedles. Second, the targets of equipment-assisted microneedle detections are summarized, as well as the objective significance, revealing the current performance and potential scenarios of these microneedles. Third, the trend towards highly integrated sensors is elaborated by emphasizing the sensing principles (colorimetric, fluorometric and electronic manner). Finally, the key challenges to be tackled and the perspectives on future development are discussed.
Subject(s)
Biosensing Techniques , Drug Delivery Systems , Microinjections , Administration, Cutaneous , NeedlesABSTRACT
Metformin is a clinically-approved anti-diabetic drug with emerging antitumor potential, but its antitumor activity is highly susceptible to local glucose abundance. Herein, we construct a nanotherapeutic platform based on biocompatible constituents to sensitize tumor cells for metformin therapy via cooperative glucose starvation. The nanoplatform was synthesized through the spontaneous biomineralization of glucose oxidase (GOx) and metformin in amorphous calcium phosphate nanosubstrate, which was further modified with polyethylene glycol and cRGD ligands. This biomineralized nanosystem could efficiently deliver the therapeutic payloads to tumor cells in a targeted and bioresponsive manner. Here GOx could catalyze the oxidation of glucose into gluconic acid and H2O2, thus depleting the glucose in tumor intracellular compartment while accelerating the release of the entrapped therapeutic payloads. The selective glucose deprivation would not only disrupt tumor energy metabolism, but also upregulate the PP2A regulatory subunit B56δ and sensitize tumor cells to the metformin-induced CIP2A inhibition, leading to efficient apoptosis induction via PP2A-GSK3ß-MCL-1 axis with negligible side effects. This study may offer new avenues for targeted tumor therapy in the clinical context.