This work demonstrates a simple approach for coating a porous polymer layer on stainless-steel (SS) microneedles characterized by a pH-responsive formulation for self-regulated drug delivery. For many drug-delivery applications, the release of therapeutic agents in an acidic microenvironment is desirable. Acid-sensitive polymers and hydrogels were extensively explored, but easily prepared polymeric microcarriers that combine acid sensitivity and biodegradability are rare. Here, we describe a simple and robust method of coating a porous polymer layer on SS microneedles (MNs) that release a model drug (lidocaine) in a pH-responsive fashion. It was constructed by packing the model drug and a pH-sensitive component (sodium bicarbonate) into the pores of the polymer layer. When this acid-sensitive formulation was exposed to the acidic microenvironment, the consequent reaction of protons (H⁺) with sodium bicarbonate (NaHCO₃) yielded CO₂. This effect generated pressure inside the pores of the coating and ruptured the thin polymer membrane, thereby releasing the encapsulated drug. Scanning electron micrographs showed that the pH-sensitive porous polymer-coated MNs exposed to phosphate-buffered saline (PBS) at pH 7.4 were characterized by closed pores. However, MNs exposed to PBS at pH 5.5 consisted of open pores and the thin membrane burst. The in vitro studies demonstrated the pH sensitivity of the drug release from porous polymer-coated MNs. Negligible release was observed for MNs in receiving media at pH 7.4. In contrast, significant release occurred when the MNs were exposed to acidic conditions (pH 5.5). Additionally, comparable results were obtained for drug release in vitro in porcine skin and in PBS. This revealed that our developed pH-responsive porous polymer-coated MNs could potentially be used for the controlled release of drug formulations in an acidic environment. Moreover, the stimuli-responsive drug carriers will enable on-demand controlled release profiles that may enhance therapeutic effectiveness and reduce systemic toxicity.

A closed-loop system imitating the function of pancreatic cells, connected to microneedles (MNs) that automatically “release” insulin in response to the blood glucose (BG) levels would be highly satisfactory for improving the quality of life and health for diabetes patients. This paper describes an easy, fast and simple technique of coating a porous polymer layer on stainless steel (SS) MNs that release insulin in a glucose-responsive fashion. It was fabricated by sealing insulin, sodium bicarbonate (a pH-sensitive element [NaHCO₃]) and glucose oxidase (glucose-specific enzymes [GOx]) into the pores of a porous polymer coating. Glucose can passively diffuse into the pores and become oxidized to gluconic acid by GOx, thereby causing a decrease in local pH. The subsequent reaction of protons with NaHCO₃ forms carbon dioxide (CO₂) which creates pressure inside the pores, thereby rupturing the thin polymer film and releasing the encapsulated insulin. Field emission scanning electron microscopy (FE-SEM) images displayed that upon the exposure of MNs to glucose-free phosphate buffer saline (PBS) with pH 7.4, the pores of the porous MNs were closed, while in MNs exposed to a hyperglycemic glucose level, the pores were opened and the thin film burst. These MNs demonstrated both in vitro (in porcine skin and PBS) and in vivo (in diabetic rats) glucose-mediated insulin release under hyperglycemic conditions with rapid responsiveness. This study validated that the release of insulin from porous MNs was effectively correlated with glucose concentration.

We present a 512-channel geometric droplet-splitting microfluidic device that involves the injection of a premixed emulsion for microsphere production. The presented microfluidic device was fabricated using conventional photolithography and polydimethylsiloxane casting. The fabricated microfluidic device consisted of 512 channels with 256 T-junctions in the last branch. Five hundred and twelve microdroplets with a narrow size distribution were produced from a single liquid droplet. The diameter and size distribution of prepared micro water droplets were 35.29 µm and 8.8% at 10 mL/h, respectively. Moreover, we attempted to prepare biocompatible microspheres for demonstrating the presented approach. The diameter and size distribution of the prepared poly (lactic-co-glycolic acid) microspheres were 6.56 µm and 8.66% at 10 mL/h, respectively. To improve the monodispersity of the microspheres, we designed an additional post array part in the 512-channel geometric droplet-splitting microfluidic device. The monodispersity of the microdroplets prepared with the microfluidic device combined with the post array part exhibited a significant improvement.

With increasing interest in induced pluripotent stem cells (iPSCs) in the field of stem cell research, highly efficient infection of somatic cells with virus factors is gaining importance. This paper presents a method of employing microfluidic devices for dynamic cell culture and virus infection in a microchannel. The closed space in the microchannel provided a better environment for viruses to diffuse and contact cell surfaces to infect cells. The microfluidic devices were fabricated by photolithography and soft lithography. NIH/3T3 fibroblast cells were cultured in the microfluidic device in static and dynamic conditions and compared with the conventional culture method of using Petri dishes. Virus infection was evaluated using an enhanced green fluorescent protein virus as a model. Dynamic culture in the microchannel showed similar growth of cells to that in Petri dish culture, but the virus infection efficiency was four-times higher. The proposed dynamic culture system could be useful in iPSC research by providing efficient virus infection tools.