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16 pages, 10247 KiB

Open AccessArticle

Morphological Changes, Antibacterial Activity, and Cytotoxicity Characterization of Hydrothermally Synthesized Metal Ions-Incorporated Nanoapatites for Biomedical Application

by Ssu-Meng Huang, Shih-Ming Liu, Wen-Cheng Chen, Chia-Ling Ko, Chi-Jen Shih and Jian-Chih Chen

Pharmaceuticals 2022, 15(7), 885; https://doi.org/10.3390/ph15070885 - 18 Jul 2022

Cited by 7 | Viewed by 2193

Abstract

The objective of this study was to prepare hydroxyapatite (HA) with potential antibacterial activity against gram-negative and gram-positive bacteria by incorporating different atomic ratios of Cu²⁺ (0.1–1.0%), Mg²⁺ (1.0–7.0%), and Zn²⁺ (1.0–7.0%) to theoretically replace Ca²⁺ ions during the [...] Read more.

The objective of this study was to prepare hydroxyapatite (HA) with potential antibacterial activity against gram-negative and gram-positive bacteria by incorporating different atomic ratios of Cu²⁺ (0.1–1.0%), Mg²⁺ (1.0–7.0%), and Zn²⁺ (1.0–7.0%) to theoretically replace Ca²⁺ ions during the hydrothermal synthesis of grown precipitated HA nanorods. This study highlights the role of comparing different metal ions on synthetic nanoapatite in regulating the antibacterial properties and toxicity. The comparisons between infrared spectra and between diffractograms have confirmed that metal ions do not affect the formation of HA phases. The results show that after doped Cu²⁺, Mg²⁺, and Zn²⁺ ions replace Ca²⁺, the ionic radius is almost the same, but significantly smaller than that of the original Ca²⁺ ions, and the substitution effect causes the lattice distance to change, resulting in crystal structure distortion and reducing crystallinity. The reduction in the length of the nanopatites after the incorporation of Cu²⁺, Mg²⁺, and Zn²⁺ ions confirmed that the metal ions were mainly substituted during the growth of the rod-shape nanoapatite Ca²⁺ distributed along the longitudinal site. The antibacterial results show that nanoapatite containing Cu²⁺ (0.1%), Mg²⁺ (3%), and Zn²⁺ (5–7%) has obvious and higher antibacterial activity against gram-positive bacteria Staphylococcus aureus within 2 days. The antibacterial effect against the gram-negative bacillus Escherichia coli is not as pronounced as against Staphylococcus aureus. The antibacterial effect of Cu²⁺ substituted Ca²⁺ with an atomic ratio of 0.1~1.0% is even better than that of Mg²⁺- and Zn²⁺- doped with 1~7% groups. In terms of cytotoxicity, nanoapatites with Cu²⁺ (~0.2%) exhibit cytotoxicity, whereas Mg²⁺- (1–5%) and Zn²⁺- (~1%) doped nanoapatites are biocompatible at low concentrations but become cytotoxic as ionic concentration increases. The results show that the hydrothermally synthesized nanoapatite combined with Cu²⁺ (0.2%), Mg²⁺ (3%), and Zn²⁺ (3%) exhibits low toxicity and high antibacterial activity, which provides a good prospect for bypassing antibiotics for future biomedical applications. Full article

(This article belongs to the Special Issue Synthesis of Metal Nanoparticles and Their Pharmaceutical Applications)

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14 pages, 4086 KiB

Open AccessArticle

Size-Dependent Antibacterial, Antidiabetic, and Toxicity of Silver Nanoparticles Synthesized Using Solvent Extraction of Rosa indica L. Petals

by Satheesh Kumar Balu, Swetha Andra, Fouad Damiri, Anandhi Sivaramalingam, Manisha Vidyavathy Sudandaradoss, Karthikeyan Kumarasamy, Kishore Bhakthavachalam, Faraat Ali, Milton Kumar Kundu, Md. Habibur Rahman, Mohammed Berrada and Simona Cavalu

Pharmaceuticals 2022, 15(6), 689; https://doi.org/10.3390/ph15060689 - 31 May 2022

Cited by 7 | Viewed by 2523

Abstract

In this study, silver nanoparticles (AgNPs) are synthesized through a green approach by employing Rosa indica L. petal (RE) extracts as reducing and stabilizing agents, which are extracted using three different solvents: ethanol (Et), acetone (Ac), and water (Aq). The phase formation of [...] Read more.

In this study, silver nanoparticles (AgNPs) are synthesized through a green approach by employing Rosa indica L. petal (RE) extracts as reducing and stabilizing agents, which are extracted using three different solvents: ethanol (Et), acetone (Ac), and water (Aq). The phase formation of the AgNPs is confirmed using X-ray diffraction (XRD). Morphological analysis is performed using a field-emission scanning electron microscope (FESEM), which reveals that the AgNPs are spherical in shape. The size is estimated using ImageJ software, which is found to be ~12, 18, and 770 nm for RE-Ac-Ag, RE-Et-Ag, and RE-Aq-Ag, respectively. The phytochemicals of Rosa indica L. petals involved in the formation of the AgNPs are studied using Fourier transform infrared spectroscopy (FTIR). Finally, these materials are studied for their antibacterial, antidiabetic, antioxidant, and hemolytic activity, as well as cell toxicity properties. The materials, RE-Ac-Ag and RE-Et-Ag, are found to be more effective than RE-Aq-Ag in inhibiting E. coli (Gram-negative bacteria) and S. aureus (Gram-positive bacteria). Hemolytic studies reveal that all of the samples show concentration-dependent activity up to 50 µg/mL. RE-Ac-Ag and RE-Et-Ag exhibit nonhemolytic behavior, whereas RE-Aq-Ag remains nonhemolytic until 100 µg/mL. The antidiabetic ability of the AgNPs is evaluated using α-amylase inhibition assay (DNSA assay) and α-glucosidase inhibition assay. The results are found to be effective, with IC₅₀ values of α-amylase and α-glycosidase being 50, 50, and 75 µg/mL for RE-Et-Ag, RE-Ac-Ag, and RE-Aq-Ag, respectively. DPPH assay shows that the AgNPs inhibited the antioxidants well, with IC₅₀ values of 40 µg/mL for RE-Et-Ag and RE-Ac-Ag and 60 µg/mL for RE-Aq-Ag. The toxicity study reveals that the AgNPs show size- and concentration-dependent behavior. Overall, it is realized from the findings that RE-Ac-Ag, RE-Et-Ag, and RE-Aq-Ag show size-dependent antibacterial, antidiabetic, and toxicity properties. Full article

(This article belongs to the Special Issue Synthesis of Metal Nanoparticles and Their Pharmaceutical Applications)

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14 pages, 4584 KiB

Open AccessArticle

Purinoceptor Targeted Cytotoxicity of Adenosine Triphosphate-Conjugated Biogenic Selenium Nanoparticles in Human Colon Cancer Cells

by Kandasamy Saravanakumar, Anbazhagan Sathiyaseelan, Xin Zhang, Soyoung Park and Myeong-Hyeon Wang

Pharmaceuticals 2022, 15(5), 582; https://doi.org/10.3390/ph15050582 - 6 May 2022

Cited by 7 | Viewed by 2485

Abstract

The adenosine triphosphate (ATP)-conjugated biogenic selenium nanoparticles (SeNPs) for P2 (purinoceptors) receptor-targeted anti-colon cancer activity were developed in this study. First, the SeNPs were synthesized using Trichoderma extracts (TE) and then conjugated with ATP to enhance their anticancer activity. The developed SeNPs had [...] Read more.

The adenosine triphosphate (ATP)-conjugated biogenic selenium nanoparticles (SeNPs) for P2 (purinoceptors) receptor-targeted anti-colon cancer activity were developed in this study. First, the SeNPs were synthesized using Trichoderma extracts (TE) and then conjugated with ATP to enhance their anticancer activity. The developed SeNPs had an oval crystalline structure with an average diameter size of 26.45 ± 1.71 d. nm, while the ATP-SeNPs were 78.6 ± 2.91 d. nm. The SeNPs contain Se, and less persistence of P while the ATP-SeNPs have high level of P, and Se in the energy-dispersive spectroscopy (EDS). Further, both nanoparticles exhibited larger sizes in the dynamic light scattering (DLS) analysis than in the transmission electron microscopy (TEM) analysis. The DLS and Fourier transform infrared spectroscopy (FTIR) results provide evidence that the amine group (–NH₂) of ATP might bind with the negatively charged SeNPs through covalent bonding. The IC₅₀ concentration was 17.25 ± 1.16 µg/mL for ATP-SeNPs and 61.24 ± 2.08 µg/mL against the caco-2 cell line. The IC₅₀ results evidenced the higher cytotoxicity of ATP-SeNPs in the caco-2 cell line than in HEK293 cells. ATP-SeNPs trigger the anticancer activity in the caco-2 cell line through the induction of mitochondrial membrane potential (MMP) loss and nucleus damage. The biocompatibility test of hemolysis and the egg CAM assay confirmed the non-toxicity of these nanoparticles. Overall, the results proved that the newly developed ATP-SeNPs exhibited higher cytotoxicity in the caco-2 cell line than SeNPs. However, further molecular and in vivo experiments are required to develop the ATP-SeNPs as a candidate drug for cancer-targeted therapeutics. Full article

(This article belongs to the Special Issue Synthesis of Metal Nanoparticles and Their Pharmaceutical Applications)

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14 pages, 4215 KiB

Open AccessArticle

Dual-Sensitive Gold-Nanocubes Platform with Synergistic Immunotherapy for Inducing Immune Cycle Using NIR-Mediated PTT/NO/IDO

by Hsin-Yi Tsao, Hung-Wei Cheng, Chia-Chi Kuo and San-Yuan Chen

Pharmaceuticals 2022, 15(2), 138; https://doi.org/10.3390/ph15020138 - 25 Jan 2022

Cited by 8 | Viewed by 3453

Abstract

Currently, the combination therapies based on immunotherapy have been rapidly developed, but the response rate has not always increased as expected. Nano-platform has become a potential strategy which can trigger multi-functions to increase immunotherapeutic efficacy via activating T-cells and photothermal effect. Herein, to [...] Read more.

Currently, the combination therapies based on immunotherapy have been rapidly developed, but the response rate has not always increased as expected. Nano-platform has become a potential strategy which can trigger multi-functions to increase immunotherapeutic efficacy via activating T-cells and photothermal effect. Herein, to avoid the self-degradation and provide pH-sensitive property, S-nitrosoglutathione (GSNO) was loaded in gold nanocubes (AuNCs) with polyacrylic acid (PAA) coating. Subsequently, the layer-by-layer (LbL) assembly of iron oxide nanoparticles (Fe₃O₄) and betanin can provide the conjugation of 1-methyl-D-tryptophan (1-M-DT) on the nanoparticle to form an NO gas-photothermal-immune nano-platform (GAPFBD) for achieving combinatory therapy of NO gas, photothermal therapy (PTT), and indoleamine 2,3-dioxygenase (IDO) immunotherapy. After irradiation by 808-nm laser, the GSNO was released under a lower pH environment due to the structural transformation of PAA and then transformed into NO production of 64.5 ± 1.6% under PTT. The combination of PTT and NO gas therapy can effectively eliminate cancer cells, resulting in a large amount of tumor-associated antigens (TAAs) compared to the individual treatment in vitro. Additionally, the released 1-M-DT inhibited IDO and combined with TAAs to enhance maturation of dendritic cells (DCs), indicating the excellent synergistic effect of PTT and NO with IDO inhibitors. These results revealed that this dual-sensitive nanoparticle presented a combination strategy of PTT/NO/IDO for the synergistic effect to promote DC maturation. Full article

(This article belongs to the Special Issue Synthesis of Metal Nanoparticles and Their Pharmaceutical Applications)

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13 pages, 2504 KiB

Open AccessArticle

Stable Luminescent Poly(Allylaminehydrochloride)-Templated Copper Nanoclusters for Selectively Turn-Off Sensing of Deferasirox in β-Thalassemia Plasma

by Hung-Ju Lin, Chun-Chi Wang, Hwang-Shang Kou, Cheng-Wei Cheng and Shou-Mei Wu

Pharmaceuticals 2021, 14(12), 1314; https://doi.org/10.3390/ph14121314 - 16 Dec 2021

Cited by 3 | Viewed by 2500

Abstract

Highly stable and facile one-pot copper nanoclusters (Cu NCs) coated with poly(allylamine hydrochloride) (PAH) have been synthesized for selectively sensing deferasirox (DFX) in β-thalassemia plasma. DFX is an important drug used for treating iron overloading in β-thalassemia, but needs to be monitored due [...] Read more.

Highly stable and facile one-pot copper nanoclusters (Cu NCs) coated with poly(allylamine hydrochloride) (PAH) have been synthesized for selectively sensing deferasirox (DFX) in β-thalassemia plasma. DFX is an important drug used for treating iron overloading in β-thalassemia, but needs to be monitored due to certain toxicity. In this study, the PAH-Cu NCs showed highly stable fluorescence with emission wavelengths at 450 nm. The DFX specifically interacted with the copper nanocluster to turn off the fluorescence of the PAH-Cu NCs, and could be selectively quantified through the fluorescence quenching effect. The linear range of DFX in plasma analyzed by PAH-Cu NCs was 1.0–100.0 µg/mL (r = 0.985). The relative standard deviation (RSD) and relative error (RE) were lower than 6.51% and 7.57%, respectively, showing excellent reproducibility of PAH-Cu NCs for sensing DFX in plasma. This method was also successfully applied for an analysis of three clinical plasma samples from β-thalassemia patients taking DFX. The data presented high similarity with that obtained through a capillary electrophoresis method. According to the results, the PAH-Cu NCs could be used as a tool for clinically sensing DFX in human plasma for clinical surveys. Full article

(This article belongs to the Special Issue Synthesis of Metal Nanoparticles and Their Pharmaceutical Applications)

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16 pages, 5671 KiB

Open AccessArticle

Graphene Oxide-Gold Nanorods Nanocomposite-Porphyrin Conjugate as Promising Tool for Cancer Phototherapy Performance

by Thabang Calvin Lebepe, Sundararajan Parani, Vuyelwa Ncapayi, Rodney Maluleke, Grace It Mwad Mbaz, Olufunto Tolulope Fanoro, Jose Rajendran Varghese, Atsuki Komiya, Tetsuya Kodama and Oluwatobi Samuel Oluwafemi

Pharmaceuticals 2021, 14(12), 1295; https://doi.org/10.3390/ph14121295 - 11 Dec 2021

Cited by 10 | Viewed by 3269

Abstract

The cancer mortality rate has increased, and conventional cancer treatments are known for having many side effects. Therefore, it is imperative to find a new therapeutic agent or modify the existing therapeutic agents for better performance and efficiency. Herein, a synergetic phototherapeutic agent [...] Read more.

The cancer mortality rate has increased, and conventional cancer treatments are known for having many side effects. Therefore, it is imperative to find a new therapeutic agent or modify the existing therapeutic agents for better performance and efficiency. Herein, a synergetic phototherapeutic agent based on a combination of photothermal and photodynamic therapy is proposed. The phototherapeutic agent consists of water-soluble cationic porphyrin (5,10,15,20-tetrakis(N-methylpyridinium-3-yl)porphyrin, TMePyP), and gold nanorods (AuNRs) anchored on graphene-oxide (GO) sheet. The TMePyP was initially synthesized by Adler method, followed by methylation, while GO and AuNRs were synthesized using Hummer’s and seed-mediated methods, respectively. The structural and optical properties of TMePyP were confirmed using UV-Vis, zeta analyzer, PL, FTIR and NMR. The formation of both GO and AuNRs was confirmed by UV-Vis-NIR, FTIR, TEM and zeta analyzer. TMePyP and AuNRs were anchored on GO to form GO@AuNRs-TMePyP nanocomposite. The as-synthesized nanocomposite was stable in RPMI and PBS medium, and, on irradiation, produced high heat than the bare AuNRs, with high photothermal efficiency. In addition, the nanocomposite produced higher singlet oxygen than TMePyP with high biocompatibility in the absence of light. These results indicated that the as-synthesized nanocomposite is a promising dual photodynamic and photothermal agent for cancer therapy. Full article

(This article belongs to the Special Issue Synthesis of Metal Nanoparticles and Their Pharmaceutical Applications)

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17 pages, 4251 KiB

Open AccessArticle

Green-Synthesized Magnesium Hydroxide Nanoparticles Induced Osteoblastic Differentiation in Bone Co-Cultured Cells

by Laura Costa Pinho, Marta M. Alves, Bruno Colaço, Maria Helena Fernandes and Catarina Santos

Pharmaceuticals 2021, 14(12), 1281; https://doi.org/10.3390/ph14121281 - 8 Dec 2021

Cited by 5 | Viewed by 3172

Abstract

In this work, magnesium hydroxide NPs were synthesized using water (Mg(OH)₂ NPs) or a rose hip (RH) extract (Mg(OH)₂RH NPs) and tested for the bone cells’ effects in co-cultured osteoblastic and osteoclastic cells, using a Transwell^® insert system, allowing [...] Read more.

In this work, magnesium hydroxide NPs were synthesized using water (Mg(OH)₂ NPs) or a rose hip (RH) extract (Mg(OH)₂RH NPs) and tested for the bone cells’ effects in co-cultured osteoblastic and osteoclastic cells, using a Transwell^® insert system, allowing reciprocal cell paracrine interactions. Behavior of each cell population was characterized for typical phenotype markers, at days 1 and 6. Cell cultures treated with osteogenic/osteoclastogenic inducers were used as positive control of cell differentiation. The NPs presented a round shape morphology with an average diameter ~90 nm (Mg(OH)₂ NPs) and below 10 nm (Mg(OH)₂RH NPs. Both NPs induced osteoblastic and osteoclastic behavior similarly to that observed in induced osteoblastic and osteoclastic cultures (positive controls). Differences between the two types of particles were evident at the gene expression level. Compared to Mg(OH)₂ NPs, the green-synthesized NPs greatly increased the expression of osteoblastic genes coding for the early markers ALP and collagen type 1 and the later transcription factor osterix, while decreasing the expression of osteoclastogenic genes, namely the essential transcription factor NFATC1, TRAP and the genes coding for the functional markers CA2 and CTSK. Overall, a positive added effect could be hypothesized for Mg(OH)₂RH NPs with potential usefulness to promote bone formation in regenerative applications. Full article

(This article belongs to the Special Issue Synthesis of Metal Nanoparticles and Their Pharmaceutical Applications)

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13 pages, 4725 KiB

Open AccessArticle

Synthesis of NIR-II Absorbing Gelatin Stabilized Gold Nanorods and Its Photothermal Therapy Application against Fibroblast Histiocytoma Cells

by Adewale Oladipo, Thabang Calvin Lebepe, Sundararajan Parani, Rodney Maluleke, Vuyelwa Ncapayi, Grace It Mwad Mbaz, Sandile Phinda Songca, Tetsuya Kodama and Oluwatobi Samuel Oluwafemi

Pharmaceuticals 2021, 14(11), 1137; https://doi.org/10.3390/ph14111137 - 9 Nov 2021

Cited by 5 | Viewed by 2847

Abstract

The excellent photothermal properties of gold nanorods (Au-NRs) make them one of the most researched plasmonic photothermal nanomaterials. However, their biological applications have been hampered greatly due to surfactant-induced cytotoxicity. We herein report a simple synthesis of highly biocompatible gelatin stabilized Au-NRs (gelatin@Au-NRs) [...] Read more.

The excellent photothermal properties of gold nanorods (Au-NRs) make them one of the most researched plasmonic photothermal nanomaterials. However, their biological applications have been hampered greatly due to surfactant-induced cytotoxicity. We herein report a simple synthesis of highly biocompatible gelatin stabilized Au-NRs (gelatin@Au-NRs) to address this issue. The optical and structural properties of the as-synthesized gelatin@Au-NRs were investigated by Zetasizer, Ultraviolet-Visible-Near Infrared (UV-Vis-NIR) spectroscopy, high-resolution transmission electron microscopy (HR-TEM), and Fourier transform infrared spectroscopy (FTIR). The as-synthesized gelatin@Au-NRs were highly crystalline and rod-like in shape with an average length and diameter of 66.2 ± 2.3 nm and 10 ± 1.6 nm, respectively. The as-synthesized gelatin@Au-NRs showed high stability in common biological media (phosphate buffer saline and Dulbecco’s Modified Eagle’s Medium) compared to CTAB capped Au-NRs. Similarly, the gelatin@Au-NRs showed an improved heat production and outstanding cell viability against two different cancer cell lines; KM-Luc/GFP (mouse fibroblast histiocytoma cell line) and FM3A-Luc (breast carcinoma cell line) compared to CTAB capped Au-NRs and PEG@Au-NRs. An in vitro photothermal therapy study against KM-Luc/GFP showed that gelatin@Au-NRs effectively destroys the cancer cells. Full article

(This article belongs to the Special Issue Synthesis of Metal Nanoparticles and Their Pharmaceutical Applications)

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13 pages, 32620 KiB

Open AccessArticle

The Antibacterial and Remineralization Effect of Silver-Containing Mesoporous Bioactive Glass Sealing and Er-YAG Laser on Dentinal Tubules Treated in a Streptococcus mutans Cultivated Environment

by Jung-Chang Kung, Wei-Hsun Wang, Yu-Ching Chiang, Yuan-Ting Yang-Wang, Yueh-Ching Wang, Wen-Cheng Chen and Chi-Jen Shih

Pharmaceuticals 2021, 14(11), 1124; https://doi.org/10.3390/ph14111124 - 4 Nov 2021

Cited by 10 | Viewed by 2955

Abstract

The aim of this study was to evaluate the remineralization and antibacterial effect of silver-containing mesoporous bioactive glass (MBG-Ag) sealing combined with Er:YAG laser irradiation on human demineralized dentin specimens in a Streptococcus mutans cultivated environment. A total of 48 human dentin specimens [...] Read more.

The aim of this study was to evaluate the remineralization and antibacterial effect of silver-containing mesoporous bioactive glass (MBG-Ag) sealing combined with Er:YAG laser irradiation on human demineralized dentin specimens in a Streptococcus mutans cultivated environment. A total of 48 human dentin specimens were randomly divided into four groups. The characteristics of MBG-Ag and the occlusion efficiency of the dentinal tubules were analyzed using X-ray diffraction patterns, Fourier-transform infrared spectroscopy, scanning electron microscope images and energy dispersive X-ray spectroscopy. Moreover, the antibacterial activity against Streptococcus mutans was evaluated by colony formation assay. The results showed that the dentin specimens with Er:YAG laser irradiation can form a melted occlusion with a size of 3–4 µm. MBG-Ag promoted the deposition of numerous crystal particles on the dentinal surface, reaching the deepest penetration depth of 70 μm. The results suggested that both MBG-Ag and laser have the ability to enhance the remineralization and precipitation of hydroxyapatite crystals. While the results showed that MBG-Ag sealing combined with the thermomechanical subablation mode of Er:YAG laser irradiation-induced dense crystalline deposition, reaching a penetration depth of more than 300 µm, silver nanoparticles without good absorption of the Er:YAG laser resulted in a heterogeneous radiated surface. Er:YAG laser irradiation with a low energy and pulse rate cannot completely inhibit the growth of S. mutans, but MBG-Ag sealing reached the bactericidal concentration. It was concluded that the simultaneous application of MBG-Ag sealing and Er:YAG laser treatment can prevent the drawbacks of their independent uses, resulting in a superior form of treatment for dentin hypersensitivity. Full article

(This article belongs to the Special Issue Synthesis of Metal Nanoparticles and Their Pharmaceutical Applications)

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16 pages, 61948 KiB

Open AccessArticle

Evaluation of Antibacterial Effects of Matrix-Induced Silver Ions against Antibiotic-Resistant ESKAPE Pathogens

by Ya-Chi Huang, Tsung-Ying Yang, Bo-Xuan Chen, Jung-Chang Kung and Chi-Jen Shih

Pharmaceuticals 2021, 14(11), 1094; https://doi.org/10.3390/ph14111094 - 28 Oct 2021

Cited by 7 | Viewed by 2877

Abstract

Recently, drug-resistant bacterial infections, especially ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.), have become a critical health issue worldwide, highlighting the emerging need for novel antibacterial agents. In this study, silver nanoparticles were extracted [...] Read more.

Recently, drug-resistant bacterial infections, especially ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.), have become a critical health issue worldwide, highlighting the emerging need for novel antibacterial agents. In this study, silver nanoparticles were extracted from silver-containing mesoporous bioactive glass (MBG-Ag) using four different matrixes, including water, phosphate buffer saline (PBS), tryptic soy broth (TSB), and taurine (Tau). The inductively coupled plasma-mass spectrometer (ICP-MS) results demonstrated that the silver concentration of Tau-Ag was the highest among the four matrixes. The Tau-Ag was also observed to have 87.35% silver ions in its X-ray photoelectron spectrometer (XPS) spectra. The micrograph of transmission electron microscope (TEM) displayed a uniform distribution of silver nanoparticles, which was confined in a smaller size compared to that in TSB-Ag. Moreover, the peak shifts observed in the Fourier-transform infrared spectrometer (FTIR) spectrum implied that the -SO₃²⁻ and -NH groups in taurine may interact with silver. A low cytotoxicity was noted for Tau-Ag, with approximately 70% of cells surviving at 0.63 mg/mL. Compared to the other three matrix-induced silver agents, Tau-Ag represented a better antibacterial effect against methicillin-resistant Staphylococcus aureus, with a minimum inhibitory concentration (MIC) value of 0.63 mg/mL and a postponed growth of 0.31 mg/mL observed. Further antibacterial examinations illustrated the presence of remarkable antibacterial activities against vancomycin-resistant Enterococcus feacium, carbapenem-resistant Klebsiella pneumoniae, carbapenem-resistant Acinetobacter baumannii, and carbapenem-resistant Pseudomonas aeruginosa. Given our observations and multiple bioactive functions of taurine (prevent patients from inflammation and oxidative-stress injuries), we anticipate that taurine matrix-induced silver ions would be a biomedical material with a high potential for combatting drug-resistant ESKAPE pathogens. Full article

(This article belongs to the Special Issue Synthesis of Metal Nanoparticles and Their Pharmaceutical Applications)

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14 pages, 2951 KiB

Open AccessArticle

Evaluation of Gallic Acid-Coated Gold Nanoparticles as an Anti-Aging Ingredient

by Yun-Zhen Wu, Yen-Yu Tsai, Long-Sen Chang and Ying-Jung Chen

Pharmaceuticals 2021, 14(11), 1071; https://doi.org/10.3390/ph14111071 - 22 Oct 2021

Cited by 31 | Viewed by 5339

Abstract

Hyperglycemic environment-induced oxidative stress-mediated matrix metalloproteinase-1 (MMP-1) plays a crucial role in the degradation of the extracellular matrix (ECM), which might contribute to premature skin aging. Synthesized, environmentally friendly gallic acid-coated gold nanoparticles (GA–AuNPs) have been evaluated as an anti-aging antioxidant. Their microstructure [...] Read more.

Hyperglycemic environment-induced oxidative stress-mediated matrix metalloproteinase-1 (MMP-1) plays a crucial role in the degradation of the extracellular matrix (ECM), which might contribute to premature skin aging. Synthesized, environmentally friendly gallic acid-coated gold nanoparticles (GA–AuNPs) have been evaluated as an anti-aging antioxidant. Their microstructure was characterized by transmission electron microscopy (TEM), which showed that GA–AuNPs are spherical when prepared at pH 11. Dynamic light scattering (DLS) analysis revealed that the average hydrodynamic diameter of a GA–AuNP is approximately 40 nm and with a zeta potential of −49.63 ± 2.11 mV. Additionally, the present data showed that GA–AuNPs have a superior ability to inhibit high glucose-mediated MMP-1-elicited type I collagen degradation in dermal fibroblast cells. Collectively, our data indicated that high-glucose-mediated ROS production was reduced upon cell treatment with GA–AuNPs, which blocked p38 MAPK/ERK-mediated c-Jun, c-Fos, ATF-2 phosphorylation, and the phosphorylation of NFκB, leading to the down-regulation of MMP-1 mRNA and protein expression in high glucose-treated cells. Our findings suggest that GA-AuNPs have a superior ability to inhibit high-glucose-mediated MMP-1-elicited ECM degradation, which highlights its potential as an anti-aging ingredient. Full article

(This article belongs to the Special Issue Synthesis of Metal Nanoparticles and Their Pharmaceutical Applications)

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19 pages, 6953 KiB

Open AccessArticle

In Vitro Evaluation of Calcium Phosphate Bone Cement Composite Hydrogel Beads of Cross-Linked Gelatin-Alginate with Gentamicin-Impregnated Porous Scaffold

by Shih-Ming Liu, Wen-Cheng Chen, Chia-Ling Ko, Hsu-Ting Chang, Ya-Shun Chen, Ssu-Meng Haung, Kai-Chi Chang and Jian-Chih Chen

Pharmaceuticals 2021, 14(10), 1000; https://doi.org/10.3390/ph14101000 - 29 Sep 2021

Cited by 15 | Viewed by 3356

Abstract

Calcium phosphate bone cement (CPC) is in the form of a paste, and its special advantage is that it can repair small and complex bone defects. In the case of open wounds, tissue debridement is necessary before tissue repair and the subsequent control [...] Read more.

Calcium phosphate bone cement (CPC) is in the form of a paste, and its special advantage is that it can repair small and complex bone defects. In the case of open wounds, tissue debridement is necessary before tissue repair and the subsequent control of wound infection; therefore, CPC composite hydrogel beads containing antibiotics provide an excellent option to fill bone defects and deliver antibiotics locally for a long period. In this study, CPC was composited with the millimeter-sized spherical beads of cross-linked gelatin–alginate hydrogels at the different ratios of 0 (control), 12.5, 25, and 50 vol.%. The hydrogel was impregnated with gentamicin and characterized before compositing with CPC. The physicochemical properties, gentamicin release, antibacterial activity, biocompatibility, and mineralization of the CPC/hydrogel composites were characterized. The compressive strength of the CPC/hydrogel composites gradually decreased as the hydrogel content increased, and the compressive strength of composites containing gentamicin had the largest decrease. The working time and setting time of each group can be adjusted to 8 and 16 min, respectively, using a hardening solution to make the composite suitable for clinical use. The release of gentamicin before the hydrogel beads was composited with CPC varied greatly with immersion time. However, a stable controlled release effect was obtained in the CPC/gentamicin-impregnated hydrogel composite. The 50 vol.% hydrogel/CPC composite had the best antibacterial effect and no cytotoxicity but had reduced cell mineralization. Therefore, the optimal hydrogel beads content can be 25 vol.% to obtain a CPC/gentamicin-impregnated hydrogel composite with adequate strength, antibacterial activity, and bio-reactivity. This CPC/hydrogel containing gentamicin is expected to be used in clinical surgery in the future to accelerate bone regeneration and prevent prosthesis infection after surgery. Full article

(This article belongs to the Special Issue Synthesis of Metal Nanoparticles and Their Pharmaceutical Applications)

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23 pages, 9941 KiB

Open AccessArticle

Effects of Hinokitiol and Dicalcium Phosphate on the Osteoconduction and Antibacterial Activity of Gelatin-Hyaluronic Acid Crosslinked Hydrogel Membrane In Vitro

by Kai-Chi Chang, Wen-Cheng Chen, Ssu-Meng Haung, Shih-Ming Liu and Chih-Lung Lin

Pharmaceuticals 2021, 14(8), 802; https://doi.org/10.3390/ph14080802 - 16 Aug 2021

Cited by 9 | Viewed by 3051

Abstract

Many hydrogel-based crosslinking membranes have been designed and tailored to meet the needs of different applications. The aim of this research is to design a bifunctional hydrogel membrane with antibacterial and osteoconducting properties to guide different tissues. The membrane uses gelatin and hyaluronic [...] Read more.

Many hydrogel-based crosslinking membranes have been designed and tailored to meet the needs of different applications. The aim of this research is to design a bifunctional hydrogel membrane with antibacterial and osteoconducting properties to guide different tissues. The membrane uses gelatin and hyaluronic acid as the main structure, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride as the crosslinker, hinokitiol as the antibacterial agent, and dicalcium phosphate anhydrous (DCPA) micron particles for osteoconduction. Results show that the hydrogel membrane with added DCPA and impregnated hinokitiol has a fixation index higher than 88%. When only a small amount of DCPA is added, the tensile strength does not decrease significantly. The tensile strength decreases considerably when a large amount of modified DCPA is added. The stress–strain curve shows that the presence of a large amount of hinokitiol in hydrogel membranes results in considerably improved deformation and toughness properties. Each group impregnated with hinokitiol exhibits obvious antibacterial capabilities. Furthermore, the addition of DCPA and impregnation with hinokitiol does not exert cytotoxicity on cells in vitro, indicating that the designed amount of DCPA and hinokitiol in this study is appropriate. After a 14-day cell culture, the hydrogel membrane still maintains a good shape because the cells adhere and proliferate well, thus delaying degradation. In addition, the hydrogel containing a small amount of DCPA has the best cell mineralization effect. The developed hydrogel has a certain degree of flexibility, degradability, and bifunctionality and is superficial. It can be used in guided tissue regeneration in clinical surgery. Full article

(This article belongs to the Special Issue Synthesis of Metal Nanoparticles and Their Pharmaceutical Applications)

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