Design and Development of Liquid Drug Reservoirs for Microneedle Delivery of Poorly Soluble Drug Molecules

The poor aqueous solubility of existing and emerging drugs is a major issue faced by the pharmaceutical industry. Water-miscible organic solvents, termed co-solvents, can be used to enhance the solubility of poorly soluble substances. Typically, drugs with poor aqueous solubility and Log P > 3 are not amenable to delivery across the skin. This study investigated the use of co-solvents as reservoirs to be used in combination with hydrogel-forming microneedles to enhance the transdermal delivery of hydrophobic compounds, namely Nile red, olanzapine and atorvastatin. A custom-made Franz cell apparatus was fabricated to test the suitability of a liquid drug reservoir in combination with polymeric microneedles. A co-solvency approach to reservoir formulation proved effective, with 83.30% ± 9.38% of Nile red dye, dissolved in 1 mL poly(ethylene glycol) (PEG 400), permeating neonatal porcine skin over 24 h. PEG 400 and propylene glycol were found to be suitable reservoir media for olanzapine and atorvastatin, with approximately 50% of each drug delivered after 24 h. This work provides crucial proof-of-concept evidence that the manipulation of microneedle reservoir properties is an effective method to facilitate microneedle-mediated delivery of hydrophobic compounds

Development of a Biodegradable Subcutaneous Implant for Prolonged Drug Delivery Using 3D Printing

Implantable drug delivery devices offer many advantages over other routes of drug delivery. Most significantly, the delivery of lower doses of drug, thus, potentially reducing side-effects and improving patient compliance. Three dimensional (3D) printing is a flexible technique, which has been subject to increasing interest in the past few years, especially in the area of medical devices. The present work focussed on the use of 3D printing as a tool to manufacture implantable drug delivery devices to deliver a range of model compounds (methylene blue, ibuprofen sodium and ibuprofen acid) in two in vitro models. Five implant designs were produced, and the release rate varied, depending on the implant design and the drug properties. Additionally, a rate controlling membrane was produced, which further prolonged the release from the produced implants, signalling the potential use of these devices for chronic conditions

3D Printing of Drug-Loaded Thermoplastic Polyurethane Meshes: A Potential Material for Soft Tissue Reinforcement in Vaginal Surgery

Current strategies to treat pelvic organ prolapse (POP) or stress urinary incontinence (SUI), include the surgical implantation of vaginal meshes. Recently, there have been multiple reports of issues generated by these meshes conventionally made of poly(propylene). This material is not the ideal candidate, due to its mechanical properties leading to complications such as chronic pain and infection. In the present manuscript, we propose the use of an alternative material, thermoplastic polyurethane (TPU), loaded with an antibiotic in combination with fused deposition modelling (FDM) to prepare safer vaginal meshes. For this purpose, TPU filaments containing levofloxacin (LFX) in various concentrations (e.g., 0.25%, 0.5%, and 1%) were produced by extrusion. These filaments were used to 3D print vaginal meshes. The printed meshes were fully characterized through different tests/analyses such as fracture force studies, attenuated total reflection-Fourier transform infrared, thermal analysis, scanning electron microscopy, X-ray microcomputed tomography (μCT), release studies and microbiology testing. The results showed that LFX was uniformly distributed within the TPU matrix, regardless the concentration loaded. The mechanical properties showed that poly(propylene) (PP) is a tougher material with a lower elasticity than TPU, which seemed to be a more suitable material due to its elasticity. In addition, the printed meshes showed a significant bacteriostatic activity on both Staphylococcus aureus and Escherichia coli cultures, minimising the risk of infection after implanting them. Therefore, the incorporation of LFX to the TPU matrix can be used to prepare anti-infective vaginal meshes with enhanced mechanical properties compared with current PP vaginal meshes

Microneedle Manufacture: Assessing Hazards and Control Measures

Transdermal microneedles have captured the attention of researchers in relation to a variety of applications, and silicone-based moulds required to produce these systems are now widely available and can be readily manufactured on the lab bench. There is however some concern over the potential for accidental needlestick injuries and, as with any sharp hazard, the potential for blood-borne pathogen transmission must be considered. This follows from recent governmental concerns over the use of microneedle systems in dermabrasion. Despite the piercing nature of the microneedle patch sharing many similarities with conventional hypodermic needles, there are notable factors that mitigate the risk of contamination. A range of microneedle systems has been prepared using micromoulding techniques, and their puncture capability assessed. A critical assessment of the potential for accidental puncture and the control measures needed to ensure safe utilisation of the patch systems is presented

A synthetic, spatially decorrelating solar irradiance generator and application to a LV grid model with high PV penetration

Residential photovoltaic (PV) technology is expected to have mass global deployment. With widespread PV in the electricity distribution grids, the variable nature of the solar resource must be understood to facilitate reliable operation. This research demonstrates that synthetic, 1-min resolution irradiance time series that vary on a spatial dimension can be generated based on the following inputs: mean hourly meteorological observations of okta, wind speed, cloud height and atmospheric pressure. The synthetic time series temporally validate against observed 1-min irradiance data for four locations—Cambourne, UK; Lerwick, UK; San Diego, CA USA; and Oahu, HI USA—when analysing 4 metrics of variability indices, ramp-rate size, irradiance magnitude frequency and clear-sky index frequency. Each metric is calculated for the modelled and observed data at each location and CDF profile correlation compared as well as applying the Kolmogorov-Smirnov (K–S) test with 99% confidence limits. CDF correlation coefficients of each metric are all above R⩾0.908, and a minimum of 90.96% of daily irradiance time series passed the K–S test. A spatial validation was performed comparing the model outputs to real observation data. The spatial correlation coefficient regression with site separation was successfully recreated with MAPE = 0.865%, RMSE = 0.01 and R=0.955. The spatial instantaneous correlation was shown to behave anisotropically when using fixed cloud direction, with different correlation in along and cross wind directions. Cloud cover states of 40–60% showed the most spatial decorrelation while 0% and 100% had the least. The model outputs are applied to a distribution grid impact model using the IEEE-8500 node test feeder. PV scenarios of 25%,50%, and 75% uptake were modelled across a 1.5×1.5 km grid. The magnitude and frequency of severe tap changing events are found to be significantly higher when using a single irradiance time series for all PV systems versus individually assigning spatially decorrelating time series

Evaluation of a minimally invasive glucose biosensor for continuous tissue monitoring

We describe here a minimally invasive glucose biosensor based on a microneedle array electrode fabricated from an epoxy-based negative photoresist (SU8 50) and designed for continuous measurement in the dermal compartment with minimal pain. These minimally invasive, continuous monitoring sensor devices (MICoMS) were produced by casting the structures in SU8 50, crosslinking and then metallising them with platinum or silver to obtain the working and reference electrodes, respectively. The metallised microneedle array electrodes were subsequently functionalised by entrapping glucose oxidase in electropolymerised polyphenol (PP) film. Sensor performance in vitro showed that glucose concentrations down to 0.5 mM could be measured with a response times (T90) of 15 s. The effect of sterilisation by Co60 irradiation was evaluated. In preparation for further clinical studies, these sensors were tested in vivo in a healthy volunteer for a period of 3–6 h. The sensor currents were compared against point measurements obtained with a commercial capillary blood glucometer. The epoxy MICoMS devices showed currents values that could be correlated with these