The advanced stimuli-responsive approaches for on-demand drug delivery systems have received tremendous attention as they have great potential to be integrated with sensing and multi-functional electronics on a flexible and stretchable single platform (all-in-one concept) in order to develop skin-integration with close-loop sensation for personalized diagnostic and therapeutic application. The wearable patch pumps have evolved from reservoir-based to matrix patch and drug-in-adhesive (single-layer or multi-layer) type. In this review, we presented the basic requirements of an artificial pancreas, surveyed the design and technologies used in commercial patch pumps available on the market and provided general information about the latest wearable patch pump. We summarized the various advanced delivery strategies with their mechanisms that have been developed to date and representative examples. Mechanical, electrical, light, thermal, acoustic and glucose-responsive approaches on patch form have been successfully utilized in the controllable transdermal drug delivery manner. We highlighted key challenges associated with wearable transdermal delivery systems, their research direction and future development trends.
Patients with type 1 diabetes and their physicians have long desired a fully closed-loop artificial pancreas (AP) system that can alleviate the burden of blood glucose regulation. Although deep reinforcement learning (DRL) methods theoretically enable adaptive insulin dosing control, they face numerous challenges, including safety and training efficiency, which have hindered their clinical application. This paper proposes a safe and efficient adaptive insulin delivery controller based on DRL. It employed ten tricks to enhance the proximal policy optimization (PPO) algorithm, improving training efficiency. Additionally, a dual safety mechanism of 'proactive guidance + reactive correction' was introduced to reduce the risks of hyperglycemia and hypoglycemia and to prevent emergencies. Performance evaluations in the Simglucose simulator demonstrate that the proposed controller achieved an 87.45% time in range (TIR) median, superior to baseline methods, with a lower incidence of hypoglycemia, notably eliminating severe hypoglycemia and treatment failures. These encouraging results indicate that the DRL-based fully closed-loop AP controller has taken an essential step toward clinical implementation.