Current progress and challenges of nanoparticle-based therapeutics in pain management

Pain is a widespread and growing health problem worldwide that exerts a considerable social and economic impact on both patients and healthcare systems and, therefore, on society in general. Although current treatment modalities include a wide variety of pharmacological and non-pharmacological approaches, due to the complexity of pain and individual differences in clinical response these options are not always effective in mitigating and relieving pain. In addition, some pain drugs such as non-steroidal anti-inflammatory drugs (NSAIDs), local anesthetics and opioids show several unfavorable side effects. Therefore, current research advances in this medical field are based on the development of potential treatments to address many of the unmet needs and to overcome the existing limitations in pain management. Nanoparticle drug delivery systems present an exciting opportunity as alternative platforms to improve efficacy and safety of medications currently in use. Herein, we review a broad range of nanoparticle formulations (organic nanostructures and inorganic nanoparticles), which have been developed to encapsulate an array of painkillers, paying special attention to the key advantages that these systems offer, (compared to the use of the free drug), as well as to the more relevant results of preclinical studies in animal models. Additionally, we will briefly discuss the impact of some of these nanoformulations in clinical trials

Towards the continuous production of Pt-based heterogeneous catalysts using microfluidic systems

The continuous production of Pt-based heterogeneous catalysts based on ultra-small (<2 nm) noble metal nanoparticles deposited on mesoporous ordered silica and their catalytic activity in VOC abatement are here reported. Microfluidic reactors can be used not only to enable the fast and controlled production of ultra-small Pt nanoparticles (NPs), but also alloyed NPs including PtPd, PtRu and PtRh can be formed in short residence times (between 60 s and 5 min). A novel continuous and homogeneous loading of these catalytic NPs on SBA-15 used as a mesoporous support is also here reported. This procedure eases the NP loading and minimizes washing post-treatments. A 12-fold decrease in the synthesis time was obtained when using this microfluidic reactor compared to the traditional batch production of Pt NPs. Microflow and batch type reactors yielded a Pt precursor conversion to generate Pt NPs with a 90% and 85% yield, respectively. Under the same conditions, the productivity of the microfluidic system (27 mg Pt NPs per h) was twice the one achieved in the conventional batch type reactor. The catalytic performance of the supported catalysts separately prepared by microfluidics and by conventional impregnation under the same conditions and with the same noble metal loading was also compared in the n-hexane abatement as a model of VOCs. Both catalysts were active in the VOC oxidation reaction but a 95% reduction in the catalyst synthesis time was obtained when using the catalysts produced in the microfluidic platform. For this reaction a long-term activity test was successfully carried out at 175 °C during 30 h on stream using the heterogeneous catalyst prepared by using the flow reactor

Single phase microreactor for the continuous, high-temperature synthesis of <4¿nm superparamagnetic iron oxide nanoparticles

The reproducibility of key nanomaterial features is essential in nanomedicine applications where small changes of physical characteristics often lead to a very different behavior. In this regard, continuous microreactors are often advocated as a means to achieve highly precise synthesis of nanomaterials. However, when the synthesis must take place at high temperatures the use of these devices becomes restricted in terms of materials and practical problems (e.g. plugging of microchannels). Here we present the continuous synthesis of ultrasmall superparamagnetic iron oxide nanoparticles (SPIONs) through a polyol-based process at high temperatures (>200 °C). The microfluidic reactor designed allows SPION production at residence times under 1 min, was able to work continuously for 8 h without channel blockage and reached high production yields by coupling microreactors using stacked plates. The effect of operating conditions was optimized to produce homogeneous particles with a narrow particle size distribution. In summary, the microreactor developed in this work enables easy-to scale up, reproducible continuous production of SPIONs

Microfluidic Continuous Approaches to Produce Magnetic Nanoparticles with Homogeneous Size Distribution

We present a gas-liquid microfluidic system as a reactor to obtain magnetite nanoparticles with an excellent degree of control regarding their crystalline phase, shape and size. Several types of microflow approaches were selected to prevent nanomaterial aggregation and to promote homogenous size distribution. The selected reactor consists of a mixer stage aided by ultrasound waves and a reaction stage using a N2-liquid segmented flow to prevent magnetite oxidation to non-magnetic phases. A milli-fluidic reactor was developed to increase the production rate where a magnetite throughput close to 450 mg/h in a continuous fashion was obtained

Smart dressings based on nanostructured fibers containing natural origin antimicrobial, anti-inflammatory, and regenerative compounds

A fast and effective wound healing process would substantially decrease medical costs, wound care supplies, and hospitalization significantly improving the patients’ quality of life. The search for effective therapeutic approaches seems to be imperative in order to avoid the aggravation of chronic wounds. In spite of all the efforts that have been made during the recent years towards the development of artificial wound dressings, none of the currently available options combine all the requirements necessary for quick and optimal cutaneous regeneration. Therefore, technological advances in the area of temporary and permanent smart dressings for wound care are required. The development of nanoscience and nanotechnology can improve the materials and designs used in topical wound care in order to efficiently release antimicrobial, anti-inflammatory and regenerative compounds speeding up the endogenous healing process. Nanostructured dressings can overcome the limitations of the current coverings and, separately, natural origin components can also overcome the drawbacks of current antibiotics and antiseptics (mainly cytotoxicity, antibiotic resistance, and allergies). The combination of natural origin components with demonstrated antibiotic, regenerative, or anti-inflammatory nanostructured materials is a promising approach to fulfil all the requirements needed for the next generation of bioactive wound dressings. Microbially compromised wounds have been treated with different essential oils, honey, cationic peptides, aloe vera, plant extracts, and other natural origin occurring antimicrobial, anti-inflammatory, and regenerative components but the available evidence is limited and insufficient to be able to draw reliable conclusions and to extrapolate those findings to the clinical practice. The evidence and some promising preliminary results indicate that future comparative studies are justified but instead of talking about the beneficial or inert effects of those natural origin occurring materials, the scientific community leads towards the identification of the main active components involved and their mechanism of action during the corresponding healing, antimicrobial, or regenerative processes and in carrying out systematic and comparative controlled tests. Once those natural origin components have been identified and their efficacy validated through solid clinical trials, their combination within nanostructured dressings can open up new avenues in the fabrication of bioactive dressings with outstanding characteristics for wound care. The motivation of this work is to analyze the state of the art in the use of different essential oils, honey, cationic peptides, aloe vera, plant extracts, and other natural origin occurring materials as antimicrobial, anti-inflammatory and regenerative components with the aim of clarifying their potential clinical use in bioactive dressings. We conclude that, for those natural occurring materials, more clinical trials are needed to reach a sufficient level of evidence as therapeutic agents for wound healing management.properties together wit

Controlled release of bupivacaine using hybrid thermoresponsive nanoparticles activated via photothermal heating

Near-infrared (NIR) responsive nanoparticles are of great interest in the biomedical field as antennas for photothermal therapy and also as triggers for on-demand drug delivery. The present work reports the preparation of hollow gold nanoparticles (HGNPs) with plasmonic absorption in the NIR region covalently bound to a thermoresponsive polymeric shell that can be used as an on-demand drug delivery system for the release of analgesic drugs. The photothermal heating induced by the nanoparticles is able to produce the collapse of the polymeric shell thus generating the release of the local anesthetic bupivacaine in a spatiotemporally controlled way. Those HGNPs contain a 10 wt.% of polymer and present excellent reversible heating under NIR light excitation. Bupivacaine released at physiological temperature (37 °C) showed a pseudo-zero order release that could be spatiotemporally modified on-demand after applying several pulses of light/temperature above and below the lower critical solution temperature (LCST) of the polymeric shell. Furthermore, the nanomaterials obtained did not displayed detrimental effects on four mammalian cell lines at doses up to 0.2 mg/mL. From the results obtained it can be concluded than this type of hybrid thermoresponsive nanoparticle can be used as an externally activated on-demand drug delivery system

Gas Slug Microfluidics: A Unique Tool for Ultrafast, Highly Controlled Growth of Iron Oxide Nanostructures

The use of nanomaterials in real life applications is often hampered by our inability to produce them in large quantities while preserving their desired properties in terms of size, shape, and crystalline phase. Here we present a novel continuous method to synthesize nanostructures with an unprecedented degree of control regarding their properties. In particular, the excellent properties of microreactors for chemical synthesis are enhanced by the introduction of gas slugs of tailored composition. Slug dynamics accelerate mixing, reduce processing times (from hours in batch processes to minutes or even seconds), and, depending on the gas atmosphere used, allows one to accurately control the crystalline phase and shape of the resulting nanostructures. Inert (N2), oxidizing (O2), or reducing (CO, H2) gases were used, leading to different morphologies and crystalline structures in a high yield, highly reproducible fabrication process

Submicronic Filtering Media Based on Electrospun Recycled PET Nanofibers: Development, Characterization, and Method to Manufacture Surgical Masks

The disposal of single-use personal protective equipment has brought a notable environmental impact in the context of the COVID-19 pandemic. During these last two years, part of the global research efforts has been focused on preventing contagion using nanotechnology. This work explores the production of filter materials with electrohydrodynamic techniques using recycled polyethylene terephthalate (PET). PET was chosen because it is one of the materials most commonly present in everyday waste (such as in food packaging, bags, or bottles), being the most frequently used thermoplastic polymer in the world. The influence of the electrospinning parameters on the filtering capacity of the resulting fabric was analyzed against both aerosolized submicron particles and microparticulated matter. Finally, we present a new scalable and straightforward method for manufacturing surgical masks by electrospinning and we validate their performance by simulating the standard conditions to which they are subjected to during use. The masks were successfully reprocessed to ensure that the proposed method is able to reduce the environmental impact of disposable face masks. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Rapid on-Chip Assembly of Niosomes: Batch versus Continuous Flow Reactors

The large-scale continuous production of niosomes remains challenging. The inherent drawbacks of batch processes such as large particle polydispersity and reduced batch-to-batch reproducibility are here overcome by using commercially available microfluidic reactors. Compared to the traditional batch-based film hydration method, herein, we demonstrate that it is possible to carry out the homogeneous, large-scale (up to 120 mg/min) production of niosomes using two different synthesis techniques (the thin film hydration method and the emulsification technique). Niosomes particle size can be controlled depending on the need by varying the synthesis temperature. The high cytocompatibility of the resulting niosomes was also demonstrated in this work on three different somatic cell lines. For the first time, the structure of the niosome multilamellar shell was also elucidated using high-resolution transmission electron microscopy (HR-STEM) as well as their colloidal stability over time (6 weeks) under different storage conditions. The morphology of cryo-protected or as-made niosomes was also evaluated by HR-STEM after freeze-drying. Finally, the dual ability of those synthetic, nonionic, surfactant-based vesicles to carry both hydrophilic and hydrophobic molecules was also here demonstrated by using laser scanning confocal microscopy

In vitro hydrolytic degradation of polyester-based scaffolds under static and dynamic conditions in a customized perfusion bioreactor

Creating biofunctional artificial scaffolds could potentially meet the demand of patients suffering from bone defects without having to rely on donors or autologous transplantation. Three-dimensional (3D) printing has emerged as a promising tool to fabricate, by computer design, biodegradable polymeric scaffolds with high precision and accuracy, using patient-specific anatomical data. Achieving controlled degradation profiles of 3D printed polymeric scaffolds is an essential feature to consider to match them with the tissue regeneration rate. Thus, achieving a thorough characterization of the biomaterial degradation kinetics in physiological conditions is needed. Here, 50:50 blends made of poly(e-caprolactone)–Poly(D, L-lactic-co-glycolic acid (PCL-PLGA) were used to fabricate cylindrical scaffolds by 3D printing (Ø 7 × 2 mm). Their hydrolytic degradation under static and dynamic conditions was characterized and quantified. For this purpose, we designed and in-house fabricated a customized bioreactor. Several techniques were used to characterize the degradation of the parent polymers: X-ray Photoelectron Spectroscopy (XPS), Gel Permeation Chro-matography (GPC), Scanning Electron Microscopy (SEM), evaluation of the mechanical properties, weigh loss measurements as well as the monitoring of the degradation media pH. Our results showed that flow perfusion is critical in the degradation process of PCL-PLGA based scaffolds implying an accelerated hydrolysis compared to the ones studied under static conditions, and up to 4 weeks are needed to observe significant degradation in polyester scaffolds of this size and chemical composition. Our degradation study and characterization methodology are relevant for an accurate design and to tailor the physicochemical properties of polyester-based scaffolds for bone tissue engineering