Effect of DMPEI coating against biofilm formation on PVC catheter surface.

Urinary tract infections (UTIs) are a significant cause of morbidity in healthcare systems and are prominently associated with applying urethral catheters, particularly in surgeries. Polyvinyl chloride (PVC) is extensively utilized in the fabrication of catheters. Biofilms, complex polymeric constructions, provide a protective milieu for cell multiplication and the enhancement of antibiotic resistance. Strategies to counteract biofilm development on medical apparatuses' surfaces incorporate antimicrobial agents such as N,N-dodecyl, and methyl polyethylenimine (DMPEI). This research endeavored to characterize the morphology of PVC and PVC-DMPEI surfaces utilizing Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM) and to gauge hydrophobicity through contact angle measurements. Employing Escherichia coli, Staphylococcus aureus, and Candida albicans in adhesion assays enabled the assessment of DMPEI's efficacy in preventing microbial adherence to PVC. Butanol successfully solubilized 2 mg.mL-1 DMPEI without altering the PVC structure. SEM results substantiated the formation of a DMPEI layer on the PVC surface, which led to decreased surface roughness, as validated by AFM, and increased hydrophilicity, as demonstrated by contact angle evaluations. E. coli, S. aureus, and C. albicans exhibited significant adhesion reduction, 89.3%, 94.3%, and 86.6% on PVC-DMPEI surfaces. SEM visualizations confirmed reduced cellular colonization on PVC-DMPEI and highlighted considerable morphological modifications in E. coli. Consequently, DMPEI films effectively minimize the adhesion of E. coli, S. aureus, and C. albicans on PVC surfaces. DMPEI, with its potential as a protective coating for innovative medical devices, promises to inhibit biofilm adherence effectively.

Efficient and easily scaled-up biosorbent based on natural and chemically modified macauba (Acrocomia aculeata) to remove Al3+, Mn2+ and Fe3+ from surface water contaminated with iron mining tailings.

The ruptures of tailings mine dams in the cities of Mariana and Brumadinho contaminated local Brazilian Rivers with toxic metals. Herein, we describe a scaled-up biosorbent based on natural macauba endocarp (NTE) and macauba endocarp chemically treated (TE) to remove Al3+, Mn2+ and Fe3+ from aqueous solutions. For the TE material: the variation of pH and temperature of water did not cause significant sorption interferences; the kinetics studies suggest a pseudo-second-order model; the adsorption isotherms revealed that the Langmuir equation was the best fit for Al3+ and Mn2+, while the Freundlich equation best described the Fe3+; and the maximum adsorption capacities were between 0.268 mg g-1 and 1.379 mg g-1. A scaled-up was carried out using an adsorption column to remove the metals from Rio Paraopeba River water samples and the results showed that both NTE and TE are potentially low cost biosorbents for removing Al3+, Mn2+ and Fe3+.

Sulfonamide-Functionalized Polymeric Nanoparticles for Enhanced In Vivo Colorectal Cancer Therapy.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in the world. 5- Fluorouracil (5-FU) is a conventional and most effective drug used in the clinic for the treatment of CRC. However, the clinical use of 5-FU is limited due to the acquired resistance and systemic toxicity, such as hepatotoxicity and gastrointestinal toxicity. OBJECTIVE: Recent advances in nanomedicine are being exploited to develop nanoparticle platforms to overcome resistance and therapeutic delivery of active molecules. Here, we developed 5-FU loaded sulfadiazine-poly(lactide-co-glycolide) nanoparticles (SUL-PLGA NPs) to be applied in the colorectal cancer model. METHODS: We assessed the in vivo efficacy of the SUL-PLGA NPs to enhance the antitumor effect of 5-FU. RESULTS: In vivo treatment with 5-FU-SUL-PLGA NPs significantly reduced tumor growth in a colon cancer xenograft model compared to free 5-FU and 5-FU loaded non-targeted NPs. Treatment with 5-FU-SUL-PLGA NPs also increased blood vessel diameters within tumors, which could act in conjunction to enhance antitumor efficacy. In addition, 5-FU-SUL-PLGA NPs significantly reduced liver mass and lung mass, which are the most common metastasis sites of CRC, and decreased liver hepatotoxicity compared to free 5-FU drug and 5-FU loaded non-targeted NPs. CONCLUSION: Our findings suggest that the use of 5-FU-SUL-PLGA NPs is a promising strategy to enhance 5-FU efficacy against CRC.

Oral Formulation of Angiotensin-(1-7) Promotes Therapeutic Actions in a Model of Eosinophilic and Neutrophilic Asthma.

The presence of eosinophils and neutrophils in the lungs of asthmatic patients is associated with the severity of the disease and resistance to corticosteroids. Thus, defective resolution of eosinophilic and neutrophilic inflammation is importantly related to exacerbation of asthma. In this study, we investigated a therapeutic action of angiotensin-(1-7) (Ang-(1-7)) in a model of asthma induced by ovalbumin (OVA) and lipopolysaccharide (LPS). Balb-c mice were sensitized and challenged with OVA. Twenty-three hours after the last OVA challenge, experimental groups received LPS, and 1 h and 7 h later, mice were treated with oral formulation of Ang-(1-7). On the next day, 45 h after the last challenge with OVA, mice were subjected to a test of motor and exploratory behavior; 3 h later, lung function was evaluated, and bronchoalveolar lavage fluid (BALF) and lungs were collected. Motor and exploratory activities were lower in OVA + LPS-challenged mice. Treatment with Ang-(1-7) improved these behaviors, normalized lung function, and reduced eosinophil, neutrophil, myeloperoxidase (MPO), eosinophilic peroxidase (EPO), and ERK1/2 phosphorylation (p-ERK1/2) in the lungs. In addition, Ang-(1-7) decreased the deposition of mucus and extracellular matrix in the airways. These results extended those of previous studies by demonstrating that oral administration of Ang-(1-7) at the peak of pulmonary inflammation can be valuable for the treatment of neutrophil- and eosinophil-mediated asthma. Therefore, these findings potentially provide a new drug to reverse the natural history of the disease, unlike the current standards of care that manage the disease symptoms at best.

Impact of DMPEI on Biofilm Adhesion on Latex Urinary Catheter.

BACKGROUND: Microorganisms can migrate from the external environment to the patient's organism through the insertion of catheters. Despite being indispensable medical device, the catheter surface can be colonized by microorganisms and become a starting point for biofilm formation. Therefore, new technologies are being developed in order to modify surfaces to prevent the adhesion and survival of microorganisms. Patents with the use of DMPEI have been filed. OBJECTIVE: In the present work, we coated latex catheter surfaces with 2 mg mL-1 DMPEI in different solvents, evaluated the wettability of the surface and the anti- biofilm activity of the coated catheter against Escherichia coli, Staphylococcus aureus, and Candida albicans. METHODS: We coated the inner and outer catheter surfaces with 2 mg mL-1 of DMPEI solubilized in butanol, dimethylformamide, and cyclohexanone and the surfaces were analyzed visually. Contact angle measurement allowed the analysis of the wettability of the surfaces. The CFU mL-1 count evaluated E. coli, S. aureus, and C. albicans adhesion onto the control and treated surfaces. RESULTS: The contact angle decreased from 50.48º to 46.93º on the inner surface and from 55.83º to 50.91º on the outer surface of latex catheters coated with DMPEI. The catheter coated with DMPEI showed anti-biofilm activity of 83%, 88%, and 93% on the inner surface and 100%, 92%, and 86% on the outer surface for E. coli, S. aureus, and C. albicans, respectively. CONCLUSION: Latex catheter coated with DMPEI efficiently impaired the biofilm formation both on the outer and inner surfaces, showing a potential antimicrobial activity along with a high anti-biofilm activity for medical devices.

Polycaprolactone nanofibers loaded oxytetracycline hydrochloride and zinc oxide for treatment of periodontal disease.

Periodontal diseases (PD) are mixed bacterial infections caused by microorganisms that colonize the tooth surface, leading to destructions at tooth-supporting tissues. Several local delivery systems, as nanofibers, have been developed for the treatment of PD. The purpose of the present study was developing polycaprolactone (PCL) nanofibers incorporating two antibacterial agents, OTC and ZnO, for use in the treatment of PD. Nanofibers were produced by electrospinning method: PCL loaded with ZnO (PCL-Z), PCL loaded with OTC (PCL-OTC), PCL loaded with OTC and ZnO (PCL-OTCz) and pristine PCL (PCL-P). The nanofibers were characterized physicochemically using different techniques. In addition, in vitro study of the OTC release from the nanofibers was performed. The PCL-OCT showed sustained release of the drug up to 10 h, releasing 100% of OTC. However, the PCL-OTCz nanofiber showed a slow release of OTC up to 120 h (5th day) with 54% of drug retention. The cytotoxicity assay showed that PCL-OTC nanofiber was slightly cytotoxic after 48 h and the other nanofibers were non-cytotoxic. The antibacterial activity of the nanofibers was evaluated by qualitative and quantitative analysis and against mixed bacterial culture, composed of four Gram-negative anaerobic bacteria involved in periodontal diseases. The disk diffusion method showed that the PCL-OTC displayed higher inhibition zone than PCL-OTCz (p < 0.001). The quantitative analysis, evaluated by broth culture, showed that the PCL-OTC and PCL-OTCz exhibited excellent activity against a mixed bacterial culture with growth inhibition of 98.0% and 97.5%, respectively. Based on these results, the PCL-OTCz nanofibers developed have great potential as a drug delivery system for the PD treatment.

Testosterone improves the osteogenic potential of a composite in vitro and in vivo.

Testosterone (T) has been suggested as a promising agent in the bone osteointegration when incorporated in a bioceramic/polymer combination for the local application. The objective of this study was to evaluate the activity of a testosterone composite of poly (lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), and biphasic calcium phosphate (BCP) as a strategy for enhancing its osteogenic effect and to evaluate tissue response to the composite implantation. PLGA/PCL/BCP/T and PLGA/PCL/BCP composites were prepared and characterized using thermal analysis. Composite morphology and surface characteristics were assessed by SEM and EDS. The evaluations of in vitro effects of testosterone composite on osteoblasts viability, alkaline phosphatase activity, collagen production, osteocalcin concentration, quantification of mineralization, and nitric oxide concentration, after 7, 14, and 21 days. Testosterone was successfully incorporated and composites showed a homogeneously distributed porous structure. The PLGA/PCL/BCP/T composite had a stimulatory effect on osteoblastic activity on the parameters evaluated, except to nitric oxide production. After 60 days, the PLGA/PCL/BCP/T composite showed no chronic inflammatory infiltrate, whereas the PLGA/PCL/BCP composite showed mild chronic inflammatory infiltrate. Angiogenesis, cellular adsorption, and fibrous deposit were observed on the surfaces of implanted composites. The composites in combination with testosterone can be exploited to investigate the use of this scaffold for bone integration.

A long-lasting oral preformulation of the angiotensin II AT1 receptor antagonist losartan.

Losartan (Los), a non-peptidic orally active agent, reduces arterial pressure through specific and selective blockade of angiotensin II receptor AT1. However, this widely used AT1 antagonist presents low bioavailability and needs once or twice a day dosage. In order to improve its bioavailability, we used the host: guest strategy based on ß-cyclodextrin (ßCD). The results suggest that Los included in ßCD showed a typical pulsatile release pattern after oral administration to rats, with increasing the levels of plasma of Los. In addition, the inclusion compound presented oral efficacy for 72 h, in contrast to Los alone, which shows antagonist effect for only 6 h. In transgenic (mREN2)L27 rats, the Los/ßCD complex reduced blood pressure for about 6 d, whereas Los alone reduced blood pressure for only 2 d. More importantly, using this host: guest strategy, sustained release of Los for over a week via the oral route can be achieved without the need for encapsulation in a polymeric carrier. The proposed preformulation increased the efficacy reducing the dose or spacing between each dose intake.

Hybrid nanofibers based on poly-caprolactone/gelatin/hydroxyapatite nanoparticles-loaded Doxycycline: Effective anti-tumoral and antibacterial activity.

Cancer is one of the leading causes of morbidity and mortality Worldwide, 19.3 million new cancer cases are expected to be identified in 2025. Among the therapeutic arsenal to cancer control one could find the Doxycycline and the nano hydroxyapatite. The Doxycycline (Dox) not only shown antibiotic effect but also exhibits a wide range of pleiotropic therapeutic properties as the control of the invasive and metastatic cancer cells characteristics. The purpose of the present study was to evaluate both cytotoxicity in vitro and antibacterial activity of electrospun Dox-loaded hybrid nanofibrous scaffolds composed by hydroxyapatite nanoparticles (nHA), poly-ε-caprolactone (PCL) and gelatin (Gel) polymers. Both nHA and Dox were dispersed into different PCL/Gel ratios (70:30, 60:40, 50:50wt%) solutions to form electrospun nanofibers. The nHA and Dox/nHA/PCL-Gel hybrid nanofibers were characterized by TEM microscopy. In vitro Dox release behavior from all of these Dox-loaded nHA/PCL-Gel nanofibers showed the same burst release profile due to the high solubility of Gel in the release medium. Antibacterial properties of nanofiber composites were evaluated using Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Porphyromonas gingivalis (P. gingivalis) bacteria. The co-delivery of nHA particles and Dox simultaneously exhibited inhibition of bacterial growth more efficiently than the delivery of either Dox or nHA at the same concentrations, indicating a synergistic effect. The results showed that cancer cell tested had different sensibility to co-delivery system. On the whole, A-431 cells were found exhibited the most pronounced synergistic effect compared to CACO-2 and 4T1 cancer cells. Based on the anticancer as well as the antimicrobial results in this study, the developed Dox/nHA/PCL-Gel composite nanofibers are suitable as a drug delivery system with potential applications in the biomedical fields.

Efficient antibacterial nanosponges based on ZnO nanoparticles and doxycycline.

Bacterial soft rot is responsible for the loss of about 25% of worldwide production in vegetables and fruits. Efforts have been made to develop an effective nanosponge with the capacity to load and release antibacterial drugs to protect plants. Based on the potential of the ZnO nanoparticles (ZnO-NPs) to achieve this goal, this study synthesized NP via the sol-gel and hydrothermal methods by controlling native defects, such as oxygen vacancies, using thermal treatments and reduced atmospheres. To characterize the ZnO NPs, X-ray diffraction (XRD), Raman spectroscopy, transmission electron microscopy (TEM), optical spectroscopy, electron paramagnetic resonance (EPR), Zeta Potential measurements and surface area with the Brunauer-Emmett-Teller (BET) method were used. The photophysical and photochemical properties via spin trapping method aligned with EPR using UVA light showed a greater formation of electron-hole pairs and hydroxyl radicals for the reduced ZnO NPs when compared with the oxidized ones. Additionally, we found that reduced ZnO-NPs have high effectively against Escherichia coli, Erwinia carotovora and Pantoea sp. bacteria using the photocatalytic effect in the UV range. Moreover, ZnO-NPs loaded with DOX release profile enables the release of DOX within 46days, where 25% was released during the first 10h followed by a second delivery phase with an interesting short-term efficacy (<1day) against E. carotovora and Pantoea sp. Bacteria. For the first time, it was demonstrated that ZnO-NPs and ZnO-NPs loaded with DOX have efficient UV photocatalytic activities against bacterial soft rot infections.

Antidiarrheal activity of extracts from Maytenus gonoclada and inhibition of Dengue virus by lupeol.

Diarrhea is an infectious disease caused by bacterial, virus, or protozoan, and dengue is caused by virus, included among the neglected diseases in several underdeveloped and developing countries, with an urgent demand for new drugs. Considering the antidiarrheal potential of species of Maytenus genus, a phytochemical investigation followed by antibacterial activity test with extracts of branches and heartwood and bark of roots from Maytenus gonoclada were conducted. Moreover, due the frequency of isolation of lupeol from Maytenus genus the antiviral activity against Dengue virus and cytotoxicity of lupeol and its complex with ß-cyclodextrins were also tested. The results indicated the bioactivity of ethyl acetate extract from branches and ethanol extract from heartwood of roots of M. gonoclada against diarrheagenic bacteria. The lupeol showed potent activity against Dengue virus and low cytotoxicity in LLC-MK2 cells, but its complex with ß-cyclodextrin was inactive. Considering the importance of novel and selective antiviral drug candidates the results seem to be promising.

Antidiarrheal activity of extracts from Maytenus gonoclada and inhibition of Dengue virus by lupeol

ABSTRACT Diarrhea is an infectious disease caused by bacterial, virus, or protozoan, and dengue is caused by virus, included among the neglected diseases in several underdeveloped and developing countries, with an urgent demand for new drugs. Considering the antidiarrheal potential of species of Maytenus genus, a phytochemical investigation followed by antibacterial activity test with extracts of branches and heartwood and bark of roots from Maytenus gonoclada were conducted. Moreover, due the frequency of isolation of lupeol from Maytenus genus the antiviral activity against Dengue virus and cytotoxicity of lupeol and its complex with β-cyclodextrins were also tested. The results indicated the bioactivity of ethyl acetate extract from branches and ethanol extract from heartwood of roots of M. gonoclada against diarrheagenic bacteria. The lupeol showed potent activity against Dengue virus and low cytotoxicity in LLC-MK2 cells, but its complex with β-cyclodextrin was inactive. Considering the importance of novel and selective antiviral drug candidates the results seem to be promising.

Magnetic nanoparticles coated with cyclodextrins and citrate for irinotecan delivery.

In the present work, we study the role of different components in the formation of more stable iron oxide magnetic nanoparticles (MNPs): ß-cyclodextrin (BCD), 2-hydroxypropyl-ß-cyclodextrin (HP) and citrate anion. MNPs formulations were characterized by FTIR, particles size measurements, zeta potential based on dynamic light scattering principle technique, X-ray powder pattern diffraction, XPS spectroscopy, transmission electron microscopy and thermogravimetric analysis. The results showed that cyclodextrins and citrate plays a key role in order to obtain a lower size of coated MNPs and proved to be an efficient strategy to obtain a more stable colloidal dispersion, avoiding the nanoparticles oxidation, enhancing the irinotecan incorporation and release. Furthermore, citrate-coated BCD-MNPs showed the same cytotoxicity of the free IRI.

Sub-additive effects of photodynamic therapy combined with erlotinib for the treatment of epidermoid carcinoma: An in vitro study.

BACKGROUND: Photodynamic therapy (PDT) is an antitumour treatment that employs the combination of a photosensitive compound, oxygen and visible light. To improve the antitumour activity of PDT, the present study used the strategy of combining PDT with erlotinib (ERL), a drug frequently used in the treatment of epidermoid carcinoma. METHODS: An MTT cell viability assay was used to evaluate the cytotoxicity of PDT combined with ERL on A431 epidermoid carcinoma cells in vitro. This study evaluated the cytotoxicity of the following treatments: red laser irradiation (660nm) at different power densities (1.25-180J/cm2), the photosensitizer methylene blue (MB) at concentrations of 0.39-100µM, PDT (12.5µM MB and laser power densities from 1.25 to 180J/cm2), and PDT (12.5µM MB and a laser density of 120J/cm2) plus ERL (1µM). RESULTS: The laser power densities that were tested showed no cytotoxicity in A431 cells. MB showed a dose-dependent cytotoxicity. In PDT, an increase in the dose of light resulted in an increase in the cytotoxicity of MB. In addition, there was a sub-additive effect between PDT and ERL compared to the effect of each therapy alone. CONCLUSIONS: The sub-additive effect between PDT and ERL suggests that their combination may be an important strategy in the treatment of epidermoid carcinoma.

Nanofibers containing tetracycline/ß-cyclodextrin: Physico-chemical characterization and antimicrobial evaluation.

This study aimed to compare two nanofiber drug delivery systems that were prepared with an electrospun process and have the potential to serve as adjuvants for the treatment of periodontal disease. The first system was composed of polycaprolactone loaded with tetracycline (TCN) and the second was composed of polycaprolactone loaded with tetracycline/ß-cyclodextrin (TCN:BCD). An antimicrobial diffusion test was performed for each of these sets of nanofibers with the microorganisms, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, both of which contribute to periodontal disease. In vitro release profiles were also obtained, and the nanofibers were characterized by thermal analysis, x-ray powder diffraction, infrared absorption spectroscopy, and scanning electron microscopy. Profiles of the TCN and TCN:BCD nanofibers showed that drug release occurred for up to 14days. However, the TCN:BCD nanofibers appeared to better protect and enhance the biological absorption of TCN due to the formation of a TCN:BCD inclusion complex.

KR12 peptide associated with cyclodextrin: Antimicrobial and antitumor activities.

The aim of this study was to determine the physical properties and antimicrobial and antiproliferative effects of the KR12 peptide complexed with 2-hydroxypropyl-ß-cyclodextrin (Hp-ßCd) in vitro. The KR12:Hp-ßCd composition was evaluated for particle size and its zeta (ζ)-potential in the presence and absence of cells. Antimicrobial activity against Streptococcus mutans, Actinobacillus actinomycetemcomitans, and Porphyromonas gingivalis for the peptide alone or associated was evaluated by minimal inhibitory concentration. The cytotoxicity of the peptide and composition toward fibroblasts, Caco-2 cells, and A431 cells was determined using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide; thiazolyl blue assay and hemolysis assay. Membrane integrity was analyzed by the lactate dehydrogenase assay. KR12:Hp-ßCd decreased the peptide concentration required for the antimicrobial effect. Moreover, this composition was able to modify cell surface parameters, such as ζ-potential, and alter the degree of hemolysis induced by KR12. However, the KR12:Hp-ßCd and KR12 alone alter the zeta potential of cells to a similar extent, suggesting a similar level of membrane interaction. The peptide alone inhibited the proliferation of Caco-2 and A431 cells more efficiently than KR12:Hp-ßCd (p < 0.001), but did not show significant cytotoxic effects via the dehydrogenase lactate assay. Both substances were effective in inhibiting the growth of odontopathogenic bacteria, as well as inhibiting Caco-2 epithelial cells. These observations highlight the potential antimicrobial and antiproliferative effects of KR12 peptide alone or associated with Hp-ßCd.

PLGA nanofibers improves the antitumoral effect of daunorubicin.

The objective of this study was to evaluate the in vivo anti-inflammatory angiogenesis activity and in vitro cytotoxicity on normal and cancer cell models of a drug delivery system consisting of poly(lactic-co-glycolic acid) nanofibers loaded with daunorubicin (PLGA-DNR) that were fabricated using an electrospinning process. The PLGA-DNR nanofibers were also characterized by thermogravimetric analysis (TGA), differential thermal analysis (DTA) and differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM) and confocal fluorescence microscopy. In vitro release of DNR from the nanofibers and its corresponding mechanism were also evaluated. Sixty-five percent of the DNR was released in an initial burst over 8h, and by 1224 h, eighty-five percent of the DNR had been released. The Higuchi model yielded the best fit to the DNR release profile over the first 8h, and the corresponding data from 24 to 1224 h could be modeled using zero-order kinetics. The PLGA-DNR nanofibers exhibited a higher cytotoxicity to A431 cells than free DNR but a cytotoxicity similar to free DNR against fibroblast cells. A higher antiangiogenic effect of PLGA nanofibers was observed in the in vivo data when compared to free DNR, and no inflammatory potential was observed for the nanofibers.

Electrospun nanofibers of polyCD/PMAA polymers and their potential application as drug delivery system.

Herein, we used an electrospinning process to develop highly efficacious and hydrophobic coaxial nanofibers based on poly-cyclodextrin (polyCD) associated with poly(methacrylic acid) (PMAA) that combines polymeric and supramolecular features for modulating the release of the hydrophilic drug, propranolol hydrochloride (PROP). For this purpose, polyCD was synthesized and characterized, and its biocompatibility was assessed using fibroblast cytotoxicity tests. Moreover, the interactions between the guest PROP molecule and both polyCD and ßCD were found to be spontaneous. Subsequently, PROP was encapsulated in uniaxial and coaxial polyCD/PMAA nanofibers. A lower PROP burst effect (reduction of approximately 50%) and higher modulation were observed from the coaxial than from the uniaxial fibers. Thus, the coaxial nanofibers could potentially be a useful strategy for developing a controlled release system for hydrophilic molecules.

Development of a calcium phosphate nanocomposite for fast fluorogenic detection of bacteria.

Current procedures for the detection and identification of bacterial infections are laborious, time-consuming, and require a high workload and well-equipped laboratories. Therefore the work presented herein developed a simple, fast, and low cost method for bacterial detection based on hydroxyapatite nanoparticles with a nutritive mixture and the fluorogenic substrate. Calcium phosphate ceramic nanoparticles were characterized and integrated with a nutritive mixture for the early detection of bacteria by visual as well as fluorescence spectroscopy techniques. The composite was obtained by combining calcium phosphate nanoparticles (Ca:P ratio, 1.33:1) with a nutritive mixture of protein hydrolysates and carbon sources, which promote fast bacterial multiplication, and the fluorogenic substrate 4-methylumbellipheryl-ß-D-glucuronide (MUG). The composite had an average particle size of 173.2 nm and did not show antibacterial activity against Gram-negative or Gram-positive bacteria. After an Escherichia coli suspension was in contact with the composite for 60-90 min, fluorescence detected under UV light or by fluorescence spectrophotometer indicated the presence of bacteria. Intense fluorescence was observed after incubation for a maximum of 90 min. Thus, this calcium phosphate nanocomposite system may be useful as a model for the development of other nanoparticle composites for detection of early bacterial adhesion.

Structural and thermodynamic characterization of doxycycline/ß-cyclodextrin supramolecular complex and its bacterial membrane interactions.

Doxycycline is a semi-synthetic antibiotic commonly used for the treatment of many aerobic and anaerobic bacteria. It inhibits the activity of matrix metalloproteinases (MMPs) and affects cell proliferation. In this study, the structural and thermodynamic parameters of free DOX and a DOX/ßCD complex were investigated, as well as their interactions and effects on Staphylococcus aureus cells and cellular cytotoxicity. Complexation of DOX and ßCD was confirmed to be an enthalpy- and entropy-driven process, and a low equilibrium constant was obtained. Treatment of S. aureus with higher concentrations of DOX or DOX/ßCD resulted in an exponential decrease in S. aureus cell size, as well as a gradual neutralization of zeta potential. These thermodynamic profiles suggest that ion-pairing and hydrogen bonding interactions occur between DOX and the membrane of S. aureus. In addition, the adhesion of ßCD to the cell membrane via hydrogen bonding is hypothesized to mediate a synergistic effect which accounts for the higher activity of DOX/ßCD against S. aureus compared to pure DOX. Lower cytotoxicity and induction of osteoblast proliferation was also associated with DOX/ßCD compared with free DOX. These promising findings demonstrate the potential for DOX/ßCD to mediate antimicrobial activity at lower concentrations, and provides a strategy for the development of other antimicrobial formulations.