Coupled Diffusion-Binding-Deformation Modelling for Phase-Transition Microneedles-Based Drug Delivery.

Phase-transition microneedles (PTMNs)-based transdermal drug delivery (TDD) is gaining popularity due to its non-invasiveness and ability to deliver a wide range of drugs. PTMNs absorb interstitial skin fluid (ISF) and transport drugs from microneedle (MNs) domain to the skin without polymer dissolution. To establish PTMNs for practical use, one needs to understand and optimise the key parameters governing drug transport mechanisms to achieve controlled drug delivery. In addressing this point, we have developed a coupled diffusion-binding-deformation model to understand the effect of physicochemical parameters (e.g., swelling capacity, drug binding) of MN and skin mechanical properties on overall drug transport behaviour. The contact mechanics at the MN and skin interface is introduced to account for the resistive force exerted by the deformed skin to MN swelling. The model is validated with the reported data of in vitro insulin delivery using polyvinyl alcohol (PVA) MN. The drug binding parameters are estimated from the fitting of the cumulative release of insulin within 6 hours of MN insertion. To predict the in vivo data of insulin delivery using the PVA MN, one-compartment model of drug pharmacokinetics is incorporated. It is shown in the paper that the model is able to predict the final insulin concentration in blood and in good agreement with the reported experimental data. The proposed model is concluded to be a tool for the predictive design and development of PTMNs-based TDD systems.

Translation of Polymeric Microneedles for Treatment of Human Diseases: Recent Trends, Progress, and Challenges.

The ongoing search for biodegradable and biocompatible microneedles (MNs) that are strong enough to penetrate skin barriers, easy to prepare, and can be translated for clinical use continues. As such, this review paper is focused upon discussing the key points (e.g., choice polymeric MNs) for the translation of MNs from laboratory to clinical practice. The review reveals that polymers are most appropriately used for dissolvable and swellable MNs due to their wide range of tunable properties and that natural polymers are an ideal material choice as they structurally mimic native cellular environments. It has also been concluded that natural and synthetic polymer combinations are useful as polymers usually lack mechanical strength, stability, or other desired properties for the fabrication and insertion of MNs. This review evaluates fabrication methods and materials choice, disease and health conditions, clinical challenges, and the future of MNs in public healthcare services, focusing on literature from the last decade.

Mathematical Modelling, Simulation and Optimisation of Microneedles for Transdermal Drug Delivery: Trends and Progress.

In the last two decades, microneedles (MNs) have received significant interest due to their potential for painless transdermal drug delivery (TDD) and minimal skin damage. MNs have found applications in a range of research and development areas in drug delivery. They have been prepared using a variety of materials and fabrication techniques resulting in MN arrays with different dimensions, shapes, and geometries for delivery of a variety of drug molecules. These parameters play crucial roles in determining the drug release profiles from the MNs. Developing mathematical modelling, simulation, and optimisation techniques is vital to achieving the desired MN performances. These will then be helpful for pharmaceutical and biotechnological industries as well as professionals working in the field of regulatory affairs focusing on MN based TDD systems. This is because modelling has a great potential to reduce the financial and time cost of both the MNs' studies and manufacturing. For example, a number of robust mathematical models for predicting the performance of the MNs in vivo have emerged recently which incorporate the roles of the structural and mechanical properties of the skin. In addressing these points, this review paper aims to highlight the current status of the MN modelling research, in particular, the modelling, simulation and optimisation of the systems for drug delivery. The theoretical basis for the simulation of MN enhanced diffusion is discussed within this paper. Thus, this review paper provides a better understanding of the modelling of the MN mediated drug delivery process.