Strategies to develop polymeric microneedles for controlled drug release.

The remarkable appeal of microneedle controlled-release systems has captivated both the academic community and pharmaceutical industry due to their great potential for achieving spatiotemporally controlled release, coupled with their the minimally invasive nature and ease of application. Over the years, scientists have dedicated their efforts to advancing microneedle systems by manipulating the physicochemical properties of matrix materials, refining microneedle designs, and interfacing with external devices to provide tailored drug release profiles in a spatiotemporally controllable manner. Expanding upon our understanding of drug release mechanisms from polymeric microneedles, which include diffusion, swelling, degradation, triggering, and targeting, there is a growing focus on manipulating the location and rate of drug release through innovative microneedle designs.

Hybrid Microneedle-Mediated Transdermal Delivery of Atorvastatin Calcium-Loaded Polymeric Micelles for Hyperlipidemia Therapy.

Hyperlipidemia has been a huge challenge to global health, leading to the cardiovascular disease, hypertension, and diabetes. Atorvastatin calcium (AC), a widely prescribed drug for hyperlipidemia, faces huge challenges with oral administration due to poor water solubility and hepatic first-pass effects, resulting in low therapeutic efficacy. In this work, we designed and developed a hybrid microneedle (MN) patch system constructed with soluble poly(vinyl alcohol) (PVA) and AC-loaded polymeric micelles (AC@PMs) for transdermal delivery of AC to enhance the hyperlipidemia therapy.

Assessing the structural stability and drug encapsulation efficiency of poly(ethylene glycol)-poly(L-lactic acid) nanoparticles loaded with atorvastatin calcium: Based on dissipative particle dynamics.

Block polymer micelles have been proven highly biocompatible and effective in improving drug utilization for delivering atorvastatin calcium. Therefore, it is of great significance to measure the stability of drug-loading nano micelles from the perspective of block polymer molecular sequence design, which would provide theoretical guidance for subsequent clinical applications. This study aims to investigate the structural stability of drug-loading micelles formed by two diblock/triblock polymers with various block sequences through coarse-grained dissipative particle dynamics (DPD) simulations.

Functional insulin aspart/insulin degludec-based microneedles for promoting postprandial glycemic control.

Insulin aspart (IAsp) and insulin degludec (IDeg), as the third generation of insulin, have a faster onset time or a more durable action period, which may simulate the secretion of insulin under physiological conditions. Microneedles (MNs) are transdermal delivery devices that may allow diabetic patients to easily deploy transdermal insulin therapy while considerably reducing injection pain. In this study, we investigated the combination of dissolving MNs with IAsp or IDeg therapy as an alternative to daily multiple insulin injections, aiming to improve glycemic control and patient compliance.

Improved pharmacodynamics of epidermal growth factor via microneedles-based self-powered transcutaneous electrical stimulation.

Epidermal growth factor is an excellent drug for promoting wound healing; however, its conventional administration strategies are associated with pharmacodynamic challenges, such as low transdermal permeability, reduction, and receptor desensitization. Here, we develop a microneedle-based self-powered transcutaneous electrical stimulation system (mn-STESS) by integrating a sliding free-standing triboelectric nanogenerator with a microneedle patch to achieve improved epidermal growth factor pharmacodynamics. We show that the mn-STESS facilitates drug penetration and utilization by using microneedles to pierce the stratum corneum.

Evaluation of Nanoparticle Stability under Blood Flow Shear.

The stability of drug-loaded nanoparticles in vivo is related to the success of the drug delivery, which is investigated as a deficiency due to the limitation of traditional experimental methods. In this study, dissipative particle dynamics (DPD), a simulation method suitable for soft matter and fluids, was used to study the stability of amphiphilic nanoparticles in the blood microenvironment. By comparing the morphology alteration of nanoparticles with various molecular topologies in the shear fluid field, we have found that branch degree and geometric symmetry would be the key factors in maintaining the nanoparticle's stability.

Thermosensitive hydrogel microneedles for controlled transdermal drug delivery.

By using the prominent merit of poly(N-isopropylacrylamide) (PNIPAm) that can reversibly switch from a linear state to a coiled state with the change in temperature, in this work, gelatin was grafted with carboxylic end-capped PNIPAm as the matrix material to fabricate a physical entanglement crosslinked hydrogel microneedles (MNs) patch that can control drug release after application on the skin. The crystallization of the drug during the fabrication process of MNs was decreased due to the thermo-reversible sol-gel transition of the matrix materials. In addition, to increase the mechanical strength of the MNs and to decrease the application time, the gelatin-g-PNIPAm (GP) MNs patch was mounted onto solid MNs to fabricate a rapidly separating MNs system (RS-GP-MNs).

Advances in self-assembling of pH-sensitive polymers: A mini review on dissipative particle dynamics.

Dissipative Particle Dynamics (DPD) is a mesoscopic simulation program used to simulate the behavior of complex fluids. This work systematically reviews the use of DPD to simulate the self-assembly process of pH-sensitive drug-loaded nanoparticles. pH-sensitive drug-loaded nanoparticles have the characteristics of good targeting and slow release in the body, which is an ideal method for treating cancer and other diseases.

Mesoscopic Simulation for the Effect of Cross-Linking Reactions on the Drug Diffusion Properties in Microneedles.

The drug diffusion issue in microneedles is the focus of its medical application. It will not only affect the distribution of drugs in the needle body but will also have an impact on the drug release performance of the microneedle. The utilization of cross-linked polymer materials to obtain the drug diffusion control has been experimentally verified as a feasible method.

Stability and Diffusion Properties of Insulin in Dissolvable Microneedles: A Multiscale Simulation Study.

Microneedle (MN) technology has been proven to be promising to become an effective drug delivery route of insulin for diabetes treatment, with the advantages of high delivery efficiency, convenient management, and minimal risk of infection. However, efforts are still required to verify the insulin activity in MNs for further clinical application. Moreover, it is also essential to study the diffusion properties of insulin to understand the ability of various MN materials to control insulin release.

Simulation study of the pH sensitive directed self-assembly of rheins for sustained drug release hydrogel.

The hydrogel formed by the directed self-assembled rhein molecules at an appropriate pH value for sustained drug release has been reported recently. Although the application in drug therapy has been experimentally verified, the research on the mechanism of the self-assembly by rhein is still incomplete. In this study, we provide a new insight of the pH-induced self-assembly mechanism employing the dissipative particle dynamics (DPD) as well as multiscale molecular simulations.

Dissipative Particle Dynamics Aided Design of Drug Delivery Systems: A Review.

A nanocarrier drug delivery system, effectively assisting to improve the solubility, bioavailability, and targeting of drugs in the human body, is a crucial means for treating cancer and other diseases. However, drug carriers usually possess multiple components and complex microstructures, and studies on the formation mechanism and internal structural details of nanocarriers are still incomplete by experimental methods. In order to overcome this adversity, the dissipative particle dynamics (DPD) simulation has been widely used owing to its unique simulation time-space scale and satisfying computing efficiency.

Multiscale simulations of drug distributions in polymer dissolvable microneedles.

Drug distribution in polymer dissolvable microneedles (MNs) is essential for enhancing the efficiency of drug delivery. In the present work, multiscale simulation was applied to study the interactions between polymer and drug molecules, which may influence the drug distribution in the MNs. In this study, Hyaluronic acid (HA) and Polyvinyl alcohol (PVA) were used to fabricate the MNs and sulfonhodamine B (SRB) was selected as the model drug.