Polyethylene Glycol-Stabilized Gold Nanostars-Loaded Microneedles for Photothermal Therapy of Melanoma

Gold nanostars (GNSs) as a photothermal agent have shown great potential for the treatment of cancers like melanoma. Irradiation of the photothermal agents with light of a suitable wavelength generates heat that induces cellular stress and protein denaturation in cancer cells. The delivery of GNSs to skin using fast dissolving microneedles (MNs) presents a promising approach for painless and convenient administration of the therapy. In this study, polyethylene glycol (PEG) stabilized GNSs able to absorb light in the near-infra red region and release heat (up to 65 °C, room temperature) are developed. The cytotoxicity of these nanoparticles is assessed before and after exposure to laser irradiation. GNSs show an instant lethal photothermal effect when tested on B16F10 melanoma cells upon irradiation with 808 nm at a power of 800 mW for 10 min. Loading the GNSs in polyvinylpyrrolidone (PVP) MNs preserves the photothermal effect of GNS and the mechanical properties of MNs. GNS-loaded PVP MNs show efficient piercing in excised porcine skin, fast dissolution in 3 min after insertion and elevation of the skin temperature after laser irradiation (808 nm, 800 mW, 10 min) to 63 °C. Consequently, PEG-stabilized GNSs and PVP MNs are a promising platform for photothermal therapy in melanoma treatment

Development of fast dissolving polymer-based microneedles for delivery of an antigenic melanoma cell membrane

Delivery of cancer cell membranes (CM) is a new approach for the activation of the immune system and the induction of immunotherapy of cancer. Local delivery of melanoma CM into skin can induce efficient immune stimulation of antigen presenting cells (APCs), such as dendritic cells. In the current study, fast dissolving microneedles (MNs) were developed for the delivery of melanoma B16F10 CM. Two polymers were tested for the fabrication of MNs: poly(methyl vinyl ether-co-maleic acid) (PMVE-MA) and hyaluronic acid (HA). The incorporation of CM in MNs was achieved through coating of the MNs using a multi-step layering procedure or the micromolding technique. The CM loading and its stabilization were improved by adding sugars (sucrose and trehalose) and a surfactant (Poloxamer 188), respectively. In an ex vivo experiment, both PMVE-MA and HA showed fast dissolutions (<30 s) after insertion into porcine skin. However, HA-MA showed better mechanical properties, namely improved resistance to fracture when submitted to a compression force. Overall, a B16F10 melanoma CM-dissolving MN system was efficiently developed as a promising device suggesting further studies in immunotherapy and melanoma applications

Development of fast dissolving polymer-based microneedles for delivery of an antigenic melanoma cell membrane

Delivery of cancer cell membranes (CM) is a new approach for the activation of the immune system and the induction of immunotherapy of cancer. Local delivery of melanoma CM into skin can induce efficient immune stimulation of antigen presenting cells (APCs), such as dendritic cells. In the current study, fast dissolving microneedles (MNs) were developed for the delivery of melanoma B16F10 CM. Two polymers were tested for the fabrication of MNs: poly(methyl vinyl ether-co-maleic acid) (PMVE-MA) and hyaluronic acid (HA). The incorporation of CM in MNs was achieved through coating of the MNs using a multi-step layering procedure or the micromolding technique. The CM loading and its stabilization were improved by adding sugars (sucrose and trehalose) and a surfactant (Poloxamer 188), respectively. In an ex vivo experiment, both PMVE-MA and HA showed fast dissolutions (<30 s) after insertion into porcine skin. However, HA-MA showed better mechanical properties, namely improved resistance to fracture when submitted to a compression force. Overall, a B16F10 melanoma CM-dissolving MN system was efficiently developed as a promising device suggesting further studies in immunotherapy and melanoma applications

Development of fast dissolving polymer-based microneedles for delivery of an antigenic melanoma cell membrane

Delivery of cancer cell membranes (CM) is a new approach for the activation of the immune system and the induction of immunotherapy of cancer. Local delivery of melanoma CM into skin can induce efficient immune stimulation of antigen presenting cells (APCs), such as dendritic cells. In the current study, fast dissolving microneedles (MNs) were developed for the delivery of melanoma B16F10 CM. Two polymers were tested for the fabrication of MNs: poly(methyl vinyl ether-co-maleic acid) (PMVE-MA) and hyaluronic acid (HA). The incorporation of CM in MNs was achieved through coating of the MNs using a multi-step layering procedure or the micromolding technique. The CM loading and its stabilization were improved by adding sugars (sucrose and trehalose) and a surfactant (Poloxamer 188), respectively. In an ex vivo experiment, both PMVE-MA and HA showed fast dissolutions (<30 s) after insertion into porcine skin. However, HA-MA showed better mechanical properties, namely improved resistance to fracture when submitted to a compression force. Overall, a B16F10 melanoma CM-dissolving MN system was efficiently developed as a promising device suggesting further studies in immunotherapy and melanoma applications

Development of fast dissolving polymer-based microneedles for delivery of an antigenic melanoma cell membrane

Delivery of cancer cell membranes (CM) is a new approach for the activation of the immune system and the induction of immunotherapy of cancer. Local delivery of melanoma CM into skin can induce efficient immune stimulation of antigen presenting cells (APCs), such as dendritic cells. In the current study, fast dissolving microneedles (MNs) were developed for the delivery of melanoma B16F10 CM. Two polymers were tested for the fabrication of MNs: poly(methyl vinyl ether-co-maleic acid) (PMVE-MA) and hyaluronic acid (HA). The incorporation of CM in MNs was achieved through coating of the MNs using a multi-step layering procedure or the micromolding technique. The CM loading and its stabilization were improved by adding sugars (sucrose and trehalose) and a surfactant (Poloxamer 188), respectively. In an ex vivo experiment, both PMVE-MA and HA showed fast dissolutions (<30 s) after insertion into porcine skin. However, HA-MA showed better mechanical properties, namely improved resistance to fracture when submitted to a compression force. Overall, a B16F10 melanoma CM-dissolving MN system was efficiently developed as a promising device suggesting further studies in immunotherapy and melanoma applications

Development of fast dissolving polymer-based microneedles for delivery of an antigenic melanoma cell membrane

Delivery of cancer cell membranes (CM) is a new approach for the activation of the immune system and the induction of immunotherapy of cancer. Local delivery of melanoma CM into skin can induce efficient immune stimulation of antigen presenting cells (APCs), such as dendritic cells. In the current study, fast dissolving microneedles (MNs) were developed for the delivery of melanoma B16F10 CM. Two polymers were tested for the fabrication of MNs: poly(methyl vinyl ether-co-maleic acid) (PMVE-MA) and hyaluronic acid (HA). The incorporation of CM in MNs was achieved through coating of the MNs using a multi-step layering procedure or the micromolding technique. The CM loading and its stabilization were improved by adding sugars (sucrose and trehalose) and a surfactant (Poloxamer 188), respectively. In an ex vivo experiment, both PMVE-MA and HA showed fast dissolutions (<30 s) after insertion into porcine skin. However, HA-MA showed better mechanical properties, namely improved resistance to fracture when submitted to a compression force. Overall, a B16F10 melanoma CM-dissolving MN system was efficiently developed as a promising device suggesting further studies in immunotherapy and melanoma applications

NIR-Emitting Gold Nanoclusters-Modified Gelatin Nanoparticles as a Bioimaging Agent in Tissue

Gold nanocluster (AuNC) synthesis using a well-distinguished polymer for nanoparticle-mediated drug delivery paves the way for developing efficient theranostics based on pharmaceutically accepted materials. Gelatin-stabilized AuNCs are synthesized and modified by glutathione for tuning the emission spectra. Addition of silver ions enhances the fluorescence, reaching also high quantum yield (26.7%). A simplified model can be proposed describing the nanoclusters' properties-structure relationship based on X-ray photoelectron spectroscopy data and synthesis sequence. Furthermore, these modifications improve fluorescence stability toward pH changes and enzymatic degradation, offering different AuNCs for various applications. The impact of nanocluster formation on gelatin structure integrity is investigated by Fourier transform infrared spectrometry and matrix-assisted laser desorption/ionization time of flight mass spectroscopy, being important to further formulate gelatin nanoparticles (GNPs). The 218 nm-sized NPs show no cytotoxicity up to 600 µg mL-1 and are imaged in skin, as a challenging autofluorescent tissue, by confocal microscopy, when transcutaneously delivered using dissolving microneedles. Linear unmixing allows simultaneous imaging of AuNCs-GNPs and skin with accurate signal separation. This underlines the great potential for bioimaging of this system to better understand nanomaterials' behavior in tissue. Additionally, it is drug delivery system also potentially serving as a theranostic system

SALT TOLERANCE OF OCIMUM BASILICUM CV. GENOVESE USING SALICYLIC ACID, SEAWEED, DRY YEAST AND MORINGA LEAF EXTRACT

To improve the salt tolerance of Genovese cultivar of sweet basil (Ocimum basilicum L.) plants, an experiment was conducted to evaluate the impact of certain growth substances (salicylic acid, seaweed extract, dry yeast and moringa leaf extract) on growth, volatile oil percentage and yield as well as chemical constituents under saline water irrigation stress conditions (control, 1000, 2000 and 4000 ppm NaCl). The obtained results revealed that the higher salinity levels (2000 and 4000 ppm NaCl) caused significant decreases in vegetative growth measurements of basil plants compared to control and the lowest salinity level (1000 ppm NaCl). Maximum reduction was observed at 4000 ppm NaCl which showed higher increase of the total phenolics and free proline contents. All recoded parameters were enhanced for plants grown under 1000 ppm NaCl. Seaweed extract was superior than other treatments in enhancing the plant tolerance to salinity which appeared in the significantly increasing of growth and volatile oil content of basil. Phenolics and proline contents were increased with salicylic acid treatment comparing with other ones. The best combination recommended as a result of the current study is treating basil plants with seaweed extract under low salinity level (1000 ppm) for improving the growth and volatile oil parameters

NIR‐Emitting Gold Nanoclusters–Modified Gelatin Nanoparticles as a Bioimaging Agent in Tissue

Gold nanocluster (AuNC) synthesis using a well‐distinguished polymer for nanoparticle‐mediated drug delivery paves the way for developing efficient theranostics based on pharmaceutically accepted materials. Gelatin‐stabilized AuNCs are synthesized and modified by glutathione for tuning the emission spectra. Addition of silver ions enhances the fluorescence, reaching also high quantum yield (26.7%). A simplified model can be proposed describing the nanoclusters\u27 properties–structure relationship based on X‐ray photoelectron spectroscopy data and synthesis sequence. Furthermore, these modifications improve fluorescence stability toward pH changes and enzymatic degradation, offering different AuNCs for various applications. The impact of nanocluster formation on gelatin structure integrity is investigated by Fourier transform infrared spectrometry and matrix‐assisted laser desorption/ionization time of flight mass spectroscopy, being important to further formulate gelatin nanoparticles (GNPs). The 218 nm‐sized NPs show no cytotoxicity up to 600 µg mL−1 and are imaged in skin, as a challenging autofluorescent tissue, by confocal microscopy, when transcutaneously delivered using dissolving microneedles. Linear unmixing allows simultaneous imaging of AuNCs–GNPs and skin with accurate signal separation. This underlines the great potential for bioimaging of this system to better understand nanomaterials\u27 behavior in tissue. Additionally, it is drug delivery system also potentially serving as a theranostic system

Double-Layered Polyvinylpyrrolidone–Poly(Methyl Vinyl Ether-Alt-Maleic Acid) based Microneedles to Deliver Meloxicam:An In Vitro, In Vivo and Short-Term Stability Evaluation Study

This study aims to explore the use of polymeric microneedles (MNs) for the transdermal delivery of drugs, a non-invasive and convenient method that avoids first-pass metabolism and gastrointestinal complications. Specifically, we develop a double-layered MN formulation using polyvinylpyrrolidone and cross-linked poly(methyl vinyl ether-alt-maleic acid), comprising a dissolvable layer and a hydrogel-forming layer. Meloxicam serves as the model drug, and no organic solvents are employed in the manufacturing process to reduce toxicity. Coherent Anti-Stokes Raman Spectroscopy (CARS) is utilized to confirm that the manufacturing process does not alter the drug's physical properties. In vitro and ex vivo studies demonstrate that the double-layered MN formulation exhibits faster drug release in the first few hours, followed by a slower release. This results in extended bioavailability in vivo compared to the commercial oral formulation of meloxicam. Preliminary results indicate that the MN formulation is also effective in pain relief and inflammation reduction. The short-term stability of the MNs formulation is also confirmed, including its mechanical properties, sustained skin permeability, drug physical properties, and distribution within MNs using CARS microscopy. Overall, these results suggest that the double-layered MN formulation holds significant potential for transdermal drug delivery, offering a safer and more effective alternative to traditional oral administration