Inkjet Printing of Pharmaceuticals.

Inkjet printing (IJP) is an additive manufacturing process that selectively deposits ink materials, layer-by-layer, to create 3D objects or 2D patterns with precise control over their structure and composition. This technology has emerged as an attractive and versatile approach to address the ever-evolving demands of personalized medicine in the healthcare industry. Although originally developed for nonhealthcare applications, IJP harnesses the potential of pharma-inks, which are meticulously formulated inks containing drugs and pharmaceutical excipients. Delving into the formulation and components of pharma-inks, the key to precise and adaptable material deposition enabled by IJP is unraveled. The review extends its focus to substrate materials, including paper, films, foams, lenses, and 3D-printed materials, showcasing their diverse advantages, while exploring a wide spectrum of therapeutic applications. Additionally, the potential benefits of hardware and software improvements, along with artificial intelligence integration, are discussed to enhance IJP's precision and efficiency. Embracing these advancements, IJP holds immense potential to reshape traditional medicine manufacturing processes, ushering in an era of medical precision. However, further exploration and optimization are needed to fully utilize IJP's healthcare capabilities. As researchers push the boundaries of IJP, the vision of patient-specific treatment is on the horizon of becoming a tangible reality.

Contact lenses that transform gold into nanoparticles for prophylaxis of light-related events and photothermal therapy.

This work describes for first time how anisotropic gold nanoparticles (AuNPs) can be spontaneously formed inside preformed contact lenses (CLs) avoiding the use of additional reductant agents (reagent-free) through a precise tunning of the monomeric composition, the saline concentration, and the application of steam heat sterilization. Protocols to generate AuNPs in solution using inorganic or small organic reductants are widely available. Differently, gold precursors interactions with polymer networks have been overlooked and, thus, the interest of chemically cross-linked hydrogels as organic reductants is still to be elucidated. In the ocular field, incorporation of AuNPs to CLs may expand their applications in prophylaxis, therapy and diagnosis. To carry out the work, a variety of hydrogels and commercially available CLs were incubated with gold salt solution without any other chemical reagent. AuNPs formation was monitored by changes in localized surface plasmon resonance (LSPR) bands and quantifying the gold sorbed. Only silicone hydrogels induced AuNPs formation at room temperature in few days; methacrylic acid red-shifted the LSPR band (550-600 nm), while monomers bearing F hindered the reduction. Storage of hydrogels in the gold precursor solution allowed a gradual formation of anisotropic AuNPs, which could be stopped at any time by washing the hydrogel with water. The developed CLs behave as efficient filters against highly penetrant light and also exhibit photoresponsiveness as demonstrated as rapid (10 s), focused mild hyperthermia when irradiated with green, red and NIR lasers.

Intracellular Biodegradation of Ag Nanoparticles, Storage in Ferritin, and Protection by a Au Shell for Enhanced Photothermal Therapy.

Despite their highly efficient plasmonic properties, gold nanoparticles are currently preferred to silver nanoparticles for biomedical applications such as photothermal therapy due to their high chemical stability in the biological environment. To confer protection while preserving their plasmonic properties, we allied the advantages of both materials and produced hybrid nanoparticles made of an anisotropic silver nanoplate core coated with a frame of gold. The efficiency of these hybrid nanoparticles (Ag@AuNPs) in photothermia was compared to monometallic silver nanoplates (AgNPs) or gold nanostars (AuNPs). The structural and functional properties of AuNPs, AgNPs, and Ag@AuNPs were investigated in environments of increasing complexity, in water suspensions, in cells, and in tumors in vivo. While AgNPs showed the greatest heating efficiency in suspension (followed by Ag@AuNPs and AuNPs), this trend was reversed intracellularly within a tissue-mimetic model. In this setup, AgNPs failed to provide consistent photothermal conversion over time, due to structural damage induced by the intracellular environment. Remarkably, the degraded Ag was found to be stored within the iron-storage ferritin protein. By contrast, the Au shell provided the Ag@AuNPs with total Ag biopersistence. As a result, photothermal therapy was successful with Ag@AuNPs in vivo in a mouse tumor model, providing the ultimate proof on Au shell's capability to shield the Ag core from the harsh biological environment and preserve its excellent heating properties.

Superhydrophobic chips for cell spheroids high-throughput generation and drug screening.

We suggest the use of biomimetic superhydrophobic patterned chips produced by a benchtop methodology as low-cost and waste-free platforms for the production of arrays of cell spheroids/microtissues by the hanging drop methodology. Cell spheroids have a wide range of applications in biotechnology fields. For drug screening, they allow studying 3D models in structures resembling real living tissues/tumors. In tissue engineering, they are suggested as building blocks of bottom-up fabricated tissues. We used the wettability contrast of the chips to fix cell suspension droplets in the wettable regions and evaluated on-chip drug screening in 3D environment. Cell suspensions were patterned in the wettable spots by three distinct methods: (1) by pipetting the cell suspension directly in each individual spot, (2) by the continuous dragging of a cell suspension on the chip, and (3) by dipping the whole chip in a cell suspension. These methods allowed working with distinct throughputs and degrees of precision. The platforms were robust, and we were able to have static or dynamic environments in each droplet. The access to cell culture media for exchange or addition/removal of components was versatile and opened the possibility of using each spot of the chip as a mini-bioreactor. The platforms' design allowed for samples visualization and high-content image-based analysis on-chip. The combinatorial analysis capability of this technology was validated by following the effect of doxorubicin at different concentrations on spheroids formed using L929 and SaOs-2 cells.

Pectin-coated chitosan microgels crosslinked on superhydrophobic surfaces for 5-fluorouracil encapsulation.

5-Fluorouracil (5-FU)-loaded chitosan microgels for oral and topical chemotherapy were prepared applying a superhydrophobic surface-based encapsulation technology. Drug-loaded chitosan dispersions were cross-linked and then coated with drug-free chitosan or pectin layers at the solid-air interface in a highly efficient and environment-friendly way. The size of the microgels (with diameters of ca. 280 and 557 µm for the chitosan seeds and pectin-coated microgels respectively) was the lowest obtained until now using similar biomimetic methodologies. The microgels were characterized regarding 5-FU release profiles in vitro in aqueous media covering the pH range of the gastrointestinal tract, and cytotoxicity against two cancer cell lines sensitive to 5-FU. Owing to their control of 5-FU release in acidic medium, calcium pectinate-coated microgels can be considered as suitable for oral administration. Growth inhibition of cancer cells by 5-FU was greater when incorporated to chitosan microgels; these being potentially useful for treatment of skin and colorectal tumors.