Metal-Assisted and Microwave-Accelerated Decrystallization of Pseudo-Tophus in Synthetic Human Joint Models.

In this paper, we tested a hypothesis that the metal-assisted and microwave-accelerated decrystallization (MAMAD) technique, based on the combined use of low-power medical microwave heating (MWH) and gold nanoparticles (Au NPs), can be used to decrystallize laboratory-prepared monosodium urate monohydrate crystal aggregate (pseudo-tophus) placed in three-dimensional (3D) synthetic human joint models. To simulate a potential treatment of chronic tophaceous gout using the MAMAD technique, we used three different 3D synthetic human joint models and assessed the percent mass reduction (PMR, i.e., decrystallization) of pseudo-tophus and microwave-induced synthetic skin patch damage after MAMAD sessions (a MAMAD session = 120 s of MWH in the presence of Au NPs). Our three synthetic joint models are: Model 1: Application of seven MAMAD sessions in a closed synthetic joint with a pseudo-bursa containing a pseudo-tophus submerged in a solution of 20 nm Au NPs followed by dehydration of pseudo-tophus after each MAMAD session to assess PMR. Model 2: Application of seven MAMAD sessions in a closed or open synthetic joint with a pseudo-bursa containing a pseudo-tophus submerged in a solution of Au NPs followed by intermittent dehydration of pseudo-tophus after seven MAMAD sessions to assess PMR. Model 3: Application of 18 MAMAD sessions in a rotated closed synthetic joint (three sides are heated separately) with a pseudo-bursa containing a pseudo-tophus submerged in a solution of Au NPs followed by dehydration after every three MAMAD sessions to assess PMR. After a single MAMAD session, pseudo-tophus exposed to MWH and Au NPs had an average PMR of 8.30% (up to an overall PMR of 15%), and microwave-induced damage to the synthetic skin can be controlled by the use of a sacrificial skin sample and by adjusting the duration and the number of the MAMAD sessions. Computational electromagnetic simulations predict a 10% absorption of electric field by the pseudo-tophus placed in the synthetic joint models, which led us to conclude that a medical microwave source with higher power than 20 W can potentially be used with the MAMAD technique.

Microwave Heating of Crystals with Gold Nanoparticles and Synovial Fluid under Synthetic Skin Patches.

Gout is a disease with elusive treatment options. Reduction of the size of l-alanine crystals as a model crystal for gouty tophi with the use of a monomode solid-state microwave was examined as a possible therapeutic aid. The effect of microwave heating on l-alanine crystals in the presence of gold nanoparticles (Au NPs) in solution and synovial fluid (SF) in a plastic pouch through a synthetic skin patch was investigated. In this regard, three experimental paradigms were employed: Paradigm 1 includes the effect of variable microwave power (5-10 W) and variable heating time (5-60 s) and Au NPs in water (20 nm size, volume of 10 µL) in a plastic pouch (1 × 2 cm2 in size). Paradigm 2 includes the effect of a variable volume of 20 nm Au NPs in a variable volume of SF up to 100 µL in a plastic pouch at a constant microwave power (10 W) for 30 s. Paradigm 3 includes the effect of constant microwave power (10 W) and microwave heating time (30 s), constant volume of Au NPs (100 µL), and variable size of Au NPs (20-200 nm) placed in a plastic pouch through a synthetic skin patch. In these experiments, an average of 60-100% reduction in the size of an l-alanine crystal (initial size = 450 µm) without damage to the synthetic skin or increasing the temperature of the samples beyond the physiological range was reported.

Ultra-Rapid Crystallization of L-alanine Using Monomode Microwaves, Indium Tin Oxide and Metal-Assisted and Microwave-Accelerated Evaporative Crystallization.

The use of indium tin oxide (ITO) and focused monomode microwave heating for the ultra-rapid crystallization of L-alanine (a model amino acid) is reported. Commercially available ITO dots (< 5 mm) attached to blank poly(methyl)methacrylate (PMMA, 5 cm in diameter with 21-well silicon isolators: referred to as the iCrystal plates) were found to withstand prolonged microwave heating during crystallization experiments. Crystallization of L-alanine was performed at room temperature (a control experiment), with the use of two microwave sources: a 2.45 GHz conventional microwave (900 W, power level 1, a control experiment) and 8 GHz (20 W) solid state, monomode microwave source with an applicator tip that focuses the microwave field to a 5-mm cavity. Initial appearance of L-alanine crystals and on iCrystal plates with ITO dots took 47 ± 2.9 min, 12 ± 7.6 min and 1.5 ± 0.5 min at room temperature, using a conventional microwave and focused monomode microwave heating, respectively. Complete evaporation of the solvent using the focused microwaves was achieved in 3.2 ± 0.5 min, which is ~52-fold and ~172-fold faster than that observed at room temperature and using conventional microwave heating, respectively. The size and number of L-alanine crystals was dependent on the type of the 21-well iCrystal plates and the microwave heating method: 33 crystals of 585 ± 137 µm in size at room temperature > 37 crystals of 542 ± 100 µm in size with conventional microwave heating > 331 crystals of 311 ± 190 µm in size with focused monomode microwave. FTIR, optical microscopy and powder X-ray diffraction analysis showed that the chemical composition and crystallinity of the L-alanine crystals did not change when exposed to microwave heating and ITO surfaces. In addition, theoretical simulations for the binding of L-alanine molecules to ITO and other metals showed the predicted nature of hydrogen bonds formed between L-alanine and these surfaces.

Metal-Assisted and Microwave-Accelerated Decrystallization: An Alternative Approach to Potential Treatment of Crystal Deposition Diseases.

Gout is a painful and prevalent crystal deposition disease caused by the overproduction of Uric Acid (UA) in the body and the atypical deposition in human synovial joints as Monosodium Urate Monohydrate (MSUM). Conventional treatments, such as NSAIDs, cyclooxygenase-2 inhibitors, and systemic glucocorticoids often present harmful side-effects and are short-lived. Long-term therapies including xanthine oxidase inhibitors and the use of uricosuric agents have been developed and aim to lower the UA serum levels in the body. As regards to post-crystals deposition, our research laboratory recently proposed and demonstrated the use of the Metal-Assisted and Microwave-Accelerated Decrystallization (MAMAD) technique for the breakdown of organic and biological crystals on planar surfaces. The MAMAD technique is based on the combined use of microwave heating and Au NPs in solution. The interactions of the Au NPs with microwave's electromagnetic field result in an increase in the kinetic energy of Au NPs, and subsequently, an increase in the collisions with target crystals placed on planar surfaces leading to rapid crystal breakdown. In this regard, our laboratory aims to develop the MAMAD technique as an alternative treatment for crystal deposition diseases, particularly gout, with minimal invasion and side-effects as compared to current treatments. In this review article, we will summarize our previous findings and provide additional data detailing the effectiveness of the MAMAD technique as a rapid and efficient method for the breakdown of gout related crystals and L-alanine crystals (a model crystal).

Microwave Heating of Synthetic Skin Samples for Potential Treatment of Gout Using the Metal-Assisted and Microwave-Accelerated Decrystallization Technique.

Physical stability of synthetic skin samples during their exposure to microwave heating was investigated to demonstrate the use of the metal-assisted and microwave-accelerated decrystallization (MAMAD) technique for potential biomedical applications. In this regard, optical microscopy and temperature measurements were employed for the qualitative and quantitative assessment of damage to synthetic skin samples during 20 s intermittent microwave heating using a monomode microwave source (at 8 GHz, 2-20 W) up to 120 s. The extent of damage to synthetic skin samples, assessed by the change in the surface area of skin samples, was negligible for microwave power of ≤7 W and more extensive damage (>50%) to skin samples occurred when exposed to >7 W at initial temperature range of 20-39 °C. The initial temperature of synthetic skin samples significantly affected the extent of change in temperature of synthetic skin samples during their exposure to microwave heating. The proof of principle use of the MAMAD technique was demonstrated for the decrystallization of a model biological crystal (l-alanine) placed under synthetic skin samples in the presence of gold nanoparticles. Our results showed that the size (initial size ∼850 µm) of l-alanine crystals can be reduced up to 60% in 120 s without damage to synthetic skin samples using the MAMAD technique. Finite-difference time-domain-based simulations of the electric field distribution of an 8 GHz monomode microwave radiation showed that synthetic skin samples are predicted to absorb ∼92.2% of the microwave radiation.