Doxycycline-loaded nanotube-modified adhesives inhibit MMP in a dose-dependent fashion

Palasuk, Jadesada; Windsor, L. Jack; Platt, Jeffrey A.; Lvov, Yuri; Geraldeli, Saulo; Bottino, Marco C.

doi:10.1007/s00784-017-2215-y

Cited by 36 publications

(45 citation statements)

References 37 publications

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“…Then, the suspensions were centrifuged and the particles were separated from the supernatant, 100 μL of each supernatant was analyzed for final doxycycline concentration. Final doxycycline concentration was subtracted from initial values to calculate loading efficacy [ 45 ]. To ascertain for doxycycline liberation, 30 mg of doxycycline loaded-NPs were suspended in 3 mL of phosphate buffer saline (PBS, pH 7.4, Fisher Scientific SL, Madrid, Spain), three different eppendorf tubes containing 1 mL of the Dox-NPs suspension were stored at 37 °C.…”

Section: Methodsmentioning

confidence: 99%

“…Seven different time-points were tested: 12, 24, 48 h, 7, 14, 21 and 28 days. Supernatans were stored at −20 °C until doxycycline concentration measuring [ 45 ]. The amount of doxycycline was assayed by high performance liquid chromatography (HPLC) (Waters Alliance 2690, Waters Corporation, Milford, MA, USA) equipped with a UV-Vis detector.…”

Section: Methodsmentioning

confidence: 99%

“…The retention time was 4.85 min. The concentration of doxycycline was calculated based on a standard curve of known levels of doxycycline at 273 nm [ 45 ].…”

Section: Methodsmentioning

confidence: 99%

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Modified Polymeric Nanoparticles Exert In Vitro Antimicrobial Activity Against Oral Bacteria

et al. 2018

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Polymeric nanoparticles were modified to exert antimicrobial activity against oral bacteria. Nanoparticles were loaded with calcium, zinc and doxycycline. Ions and doxycycline release were measured by inductively coupled plasma optical emission spectrometer and high performance liquid chromatography. Porphyromonas gingivalis, Lactobacillus lactis, Streptoccocus mutans, gordonii and sobrinus were grown and the number of bacteria was determined by optical density. Nanoparticles were suspended in phosphate-buffered saline (PBS) at 10, 1 and 0.1 mg/mL and incubated with 1.0 mL of each bacterial suspension for 3, 12, and 24 h. The bacterial viability was assessed by determining their ability to cleave the tetrazolium salt to a formazan dye. Data were analyzed by ANOVA and Scheffe’s F (p < 0.05). Doxycycline doping efficacy was 70%. A burst liberation effect was produced during the first 7 days. After 21 days, a sustained release above 6 µg/mL, was observed. Calcium and zinc liberation were about 1 and 0.02 µg/mL respectively. The most effective antibacterial material was found to be the Dox-Nanoparticles (60% to 99% reduction) followed by Ca-Nanoparticles or Zn-Nanoparticles (30% to 70% reduction) and finally the non-doped nanoparticles (7% to 35% reduction). P. gingivalis, S. mutans and L. lactis were the most susceptible bacteria, being S. gordonii and S. sobrinus the most resistant to the tested nanoparticles.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Modified Polymeric Nanoparticles Exert In Vitro Antimicrobial Activity Against Oral Bacteria

et al. 2018

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“…Doxycycline, a chemically modified tetracycline, is a cheap drug with quite safe profile. It's the only MMP-inhibitor in a concentration dependent-manner, approved by the U.S. Food and Drug Administration for the treatment of periodontal disease 7 . It is composed of a four-ring core with an 4 attached dimethyl amino group at the C4 carbon on the upper site of the molecule.…”

Section: Vegf Doxycycline Metastasismentioning

confidence: 99%

The anti-neoplastic effect of Doxycycline in Osteosarcoma as a Metalloproteinase (MMP)-inhibitor. A systematic review

Hadjimichael

Foukas

Savvidou

et al. 2019

Preprint

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Background Osteosarcoma is as a very aggressive primary bone tumor, affecting mainly young populations. Most cases diagnosed have distant macro and micro-metastases at the time of diagnosis. Surgical resection with neoadjuvant and adjuvant therapies improve overall and disease-free survival of patients. Doxycycline, a synthetic tetracycline has been found to act either as an antibiotic drug as well as a chemotherapeutic agent. Its anti-neoplastic role has been proven to be extremely significant in various types of cancer like prostate, intestinal, central neural system cancers and osteosarcoma. Inhibition of metalloproteinases (MMPs) in different stages of tumor expansion is the most well understood mechanism. MMPs are secreted molecules from various normal cells like fibroblasts, leucocytes and vascular smooth muscles but also from cells with high proliferative potential like tumor cells. In osteosarcoma, MMPs have been found to be overexpressed. MMPs help osteosarcoma cells to survive, grow and give metastases in distant sites, mainly in lungs. Doxycycline, blocks extracellular matrix and basic membranes degradation by suppressing MMPs function. As a consequence, osteosarcoma cells lose their ability to invade and give metastases. Additionally, doxycycline eliminates the secretion of vascular endothelial growth factor (VEGF) and deprives the supply of circulating nutritious components, by its anti-angiogenesis action. The aim of this review is to evaluate doxycycline’s action against osteosarcoma cells as an MMP-inhibitor and interpret its usage as a chemotherapeutic agent. Methods We checked PubMed and Google Scholar for recent published data, on the tumor-supportive role of MMPs and VEGF in osteosarcoma cells. We further studied published experimental trials, on the role of doxycycline as a tumor-suppressive agent via MMPs and VEGF inhibition. Results MMPs and VEGF have been found to play a fundamental role in osteosarcoma cells survival and its high aggressiveness by in vitro, in vivo and clinical trials. Nevertheless, Doxycycline proved its tumor-suppressive effect, by in vivo experimental trials in various cancers, but not yet in osteosarcoma. Conclusion Doxycycline remains a promising chemotherapeutic agent against osteosarcoma, via MMPs inhibition, showing of the need, for further in vivo and clinical trials to carried out in the future. Key Words: Osteosarcoma, Metalloproteinase, VEGF, Doxycycline, Metastasis

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“…HNT is a “green” biocompatible nanomaterial characterized by very low cytotoxicity [ 18 ]. Furthermore, it acts as “biologically-safe” reservoirs for the encapsulation and controlled release of a variety of therapeutic drugs [ 15 , 19 ], bioactive molecules [ 20 ] and matrix metalloproteinase inhibitors [ 21 , 22 ]. Active principles released by halloysite may last 30 to 100 times more than when these were incorporated alone or using some different nanocarriers in polymer nanocomposite [ 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Physicochemical and Microbiological Assessment of an Experimental Composite Doped with Triclosan-Loaded Halloysite Nanotubes

et al. 2018

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This study is aimed at evaluating the effects of triclosan-encapsulated halloysite nanotubes (HNT/TCN) on the physicochemical and microbiological properties of an experimental dental composite. A resin composite doped with HNT/TCN (8% w/w), a control resin composite without nanotubes (HNT/TCN-0%) and a commercial nanofilled resin (CN) were assessed for degree of conversion (DC), flexural strength (FS), flexural modulus (FM), polymerization stress (PS), dynamic thermomechanical (DMA) and thermogravimetric analysis (TGA). The antibacterial properties (M) were also evaluated using a 5-day biofilm assay (CFU/mL). Data was submitted to one-way ANOVA and Tukey tests. There was no significant statistical difference in DC, FM and RU between the tested composites (p > 0.05). The FS and CN values attained with the HNT/TCN composite were higher (p < 0.05) than those obtained with the HNT/TCN-0%. The DMA analysis showed significant differences in the TAN δ (p = 0.006) and Tg (p = 0) between the groups. TGA curves showed significant differences between the groups in terms of degradation (p = 0.046) and weight loss (p = 0.317). The addition of HNT/TCN induced higher PS, although no significant antimicrobial effect was observed (p = 0.977) between the groups for CFUs and (p = 0.557) dry weight. The incorporation of HNT/TCN showed improvements in physicochemical and mechanical properties of resin composites. Such material may represent an alternative choice for therapeutic restorative treatments, although no significance was found in terms of antibacterial properties. However, it is possible that current antibacterial tests, as the one used in this laboratory study, may not be totally appropriate for the evaluation of resin composites, unless accompanied with aging protocols (e.g., thermocycling and load cycling) that allow the release of therapeutic agents incorporated in such materials.

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Doxycycline-loaded nanotube-modified adhesives inhibit MMP in a dose-dependent fashion

Abstract: Doxycycline released from the nanotube-modified adhesives inhibited MMP activity in a concentration-dependent fashion. Therefore, the proposed nanotube-modified adhesive may hold clinical potential as a strategy to preserve resin/dentin bond stability.

Cited by 36 publications

References 37 publications

Modified Polymeric Nanoparticles Exert In Vitro Antimicrobial Activity Against Oral Bacteria

Modified Polymeric Nanoparticles Exert In Vitro Antimicrobial Activity Against Oral Bacteria

The anti-neoplastic effect of Doxycycline in Osteosarcoma as a Metalloproteinase (MMP)-inhibitor. A systematic review

Physicochemical and Microbiological Assessment of an Experimental Composite Doped with Triclosan-Loaded Halloysite Nanotubes

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