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.

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.

Neuroprotection by post-stroke administration of an oral formulation of angiotensin-(1-7) in ischaemic stroke.

NEW FINDINGS: What is the central question of this study? Angiotensin-(1-7) decreases cerebral infarct volume and improves neurological function when delivered centrally before and during ischaemic stroke. Here, we assessed the neuroprotective effects of angiotensin-(1-7) when delivered orally post-stroke. What is the main finding and its importance? We show that oral delivery of angiotensin-(1-7) attenuates cerebral damage induced by middle cerebral artery occlusion in rats, without affecting blood pressure or cerebral blood flow. Importantly, these treatments begin post-stroke at times coincident with the treatment window for tissue plasminogen activator, providing supporting evidence for clinical translation of this new therapeutic strategy. ABSTRACT: As a target for stroke therapies, the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas [ACE2/Ang-(1-7)/Mas] axis of the renin-angiotensin system can be activated chronically to induce neuroprotective effects, in opposition to the deleterious effects of angiotensin II via its type 1 receptor. However, more clinically relevant treatment protocols with Ang-(1-7) that involve its systemic administration beginning after the onset of ischaemia have not been tested. In this study, we tested systemic post-stroke treatments using a molecule where Ang-(1-7) is included within hydroxypropyl-ß-cyclodextrin [HPßCD-Ang-(1-7)] as an orally bioavailable treatment. In three separate protocols, HPßCD-Ang-(1-7) was administered orally to Sprague-Dawley rats after induction of ischaemic stroke by endothelin-1-induced middle cerebral artery occlusion: (i) to assess its effects on cerebral damage and behavioural deficits; (ii) to determine its effects on cardiovascular parameters; and (iii) to determine whether it altered cerebral blood flow. The results indicate that post-stroke oral administration of HPßCD-Ang-(1-7) resulted in 25% reductions in cerebral infarct volumes and improvement in neurological functions (P < 0.05), without inducing any alterations in blood pressure, heart rate or cerebral blood flow. In conclusion, Ang-(1-7) treatment using an oral formulation after the onset of ischaemia induces significant neuroprotection in stroke and might represent a viable approach for taking advantage of the protective ACE2/Ang-(1-7)/Mas axis in this disease.

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.

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.

Chronic oral administration of Ang-(1-7) improves skeletal muscle, autonomic and locomotor phenotypes in muscular dystrophy.

Muscular dystrophies are a group of heterogeneous genetic disorders that cause progressive muscle weakness and wasting, dilated cardiomyopathy and early mortality. There are different types of muscular dystrophies with varying aetiologies but they all have a common hallmark of myofibre degeneration, atrophy and decreased mobility. Mutation in Sgcd (sarcoglycan-δ), a subunit of dystrophin glycoprotein complex, causes LGMD2F (limb girdle muscular dystrophy 2F). Previously, we have reported that Sgcd-deficient (Sgcd-/-) mice exhibit AngII (angiotensin II)-induced autonomic and skeletal muscle dysfunction at a young age, which contributes to onset of dilated cardiomyopathy and mortality at older ages. Two counter-regulatory RAS (renin-angiotensin system) pathways have been identified: deleterious actions of AngII acting on the AT1R (AngII type 1 receptor) compared with the protective actions of Ang-(1-7) [angiotensin-(1-7)] acting on the receptor Mas. We propose that the balance between the AngII/AT1R and Ang-(1-7)/Mas axes is disturbed in Sgcd-/- mice. Control C57BL/6J and Sgcd-/- mice were treated with Ang-(1-7) included in hydroxypropyl ß-cyclodextrin (in drinking water) for 8-9 weeks beginning at 3 weeks of age. Ang-(1-7) treatment restored the AngII/AT1R compared with Ang-(1-7)/Mas balance, decreased oxidative stress and fibrosis in skeletal muscle, increased locomotor activity, and prevented autonomic dysfunction without lowering blood pressure in Sgcd-/- mice. Our results suggest that correcting the early autonomic dysregulation by administering Ang-(1-7) or enhancing its endogenous production may provide a novel therapeutic approach in muscular dystrophy.

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.

An oral formulation of angiotensin-(1-7) reverses corpus cavernosum damages induced by hypercholesterolemia.

INTRODUCTION: The renin angiotensin system plays a crucial role in erectile function. It has been shown that elevated angiotensin-II levels contribute to the development of erectile dysfunction (ED). Oppositely, angiotensin-(1-7) (Ang-[1-7]) mediates penile erection by activation of receptor Mas. Recently, we have developed a formulation based on Ang-(1-7) inclusion in cyclodextrin (CyD) [Ang-(1-7)-CyD], which allows for the oral administration of Ang-(1-7). AIM: In the present study, we evaluated the effects of chronic treatment with Ang-(1-7)-CyD on penile fibrosis, oxidative stress, and endothelial function in hypercholesterolemic mice. METHODS: Apolipoprotein(Apo)E-/- mice fed a Western-type diet for 11 weeks received Ang-(1-7)-CyD or vehicle during the final 3 weeks. Collagen content and reactive oxygen species (ROS) production within the corpus cavernosum were evaluated by Sirius red and dihydroethidium staining, respectively. Protein expression of neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS), nicotinamide adenine dinucleotide phosphate (NADPH) subunits (p67-phox and p22-phox), and AT1 and Mas receptors in the penis was assessed by Western blotting. Nitric oxide (NO) production was measured by Griess assay in the mice serum. Cavernosal strips were mounted in an isometric organ bath to evaluate the endothelial function. MAIN OUTCOME MEASURES: The effect of Ang-(1-7)-CyD treatment on penile fibrosis, oxidative stress, and endothelial function in hypercholesterolemia-induced ED. RESULTS: Ang-(1-7)-CyD treatment reduced collagen content in the corpus cavernosum of ApoE-/- mice. This effect was associated with an attenuation of ROS production and a diminished expression of NADPH. Furthermore, Ang-(1-7)-CyD treatment augmented the expression of nNOS and eNOS in the penis and elevated vascular NO production. Importantly, these effects were accompanied by an improvement in cavernosal endothelial function. CONCLUSION: Long-term treatment with Ang-(1-7)-CyD reduces penile fibrosis associated with attenuation of oxidative stress. Additionally, cavernosal endothelial function in hypercholesterolemic mice was markedly improved. These results suggest that Ang-(1-7)-CyD might have significant therapeutic benefits for the treatment of erectile dysfunction.

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+.

Superstructure based on ß-CD self-assembly induced by a small guest molecule.

The size, shape and surface chemistry of nanoparticles play an important role in cellular interaction. Thus, the main objective of the present study was the determination of the ß-cyclodextrin (ß-CD) self-assembly thermodynamic parameters and its structure, aiming to use these assemblies as a possible controlled drug release system. Light scattering measurements led us to obtain the ß-CD's critical aggregation concentration (cac) values, and consequently the thermodynamic parameters of the ß-CD spontaneous self-assembly in aqueous solution: Δ(agg)G(o) = -16.31 kJ mol(-1), Δ(agg)H(o) = -26.48 kJ mol(-1) and TΔ(agg)S(o) = -10.53 kJ mol(-1) at 298.15 K. Size distribution of the self-assembled nanoparticles below and above cac was 1.5 nm and 60-120 nm, respectively. The number of ß-CD molecules per cluster and the second virial coefficient were identified through Debye's plot and molecular dynamic simulations proposed the three-fold assembly for this system below cac. Ampicillin (AMP) was used as a drug model in order to investigate the key role of the guest molecule in the self-assembly process and the ß-CD:AMP supramolecular system was studied in solution, aiming to determine the structure of the supramolecular aggregate. Results obtained in solution indicated that the ß-CD's cac was not affected by adding AMP. Moreover, different complex stoichiometries were identified by nuclear magnetic resonance and isothermal titration calorimetry experiments.

Effect of testosterone incorporation on cell proliferation and differentiation for polymer-bioceramic composites.

In the current study, we characterized the polycaprolactone (PCL), poly(lactic acid-co-glycolic acid) (PLGA), and biphasic calcium phosphate (BCP) composites coated with testosterone propionate (T) using Fourier transform infrared spectroscopy (FTIR) and powder X-ray diffraction (XRD). Osteoblastic cells were seeded with PCL/BCP, PCL/BCP/T, PLGA/PCL/BCP and PLGA/PCL/BCP/T scaffolds, and cell viability, proliferation, differentiation and adhesion were analyzed. The results of physic-chemical experiments showed no displacements or suppression of bands in the FTIR spectra of scaffolds. The XRD patterns of the scaffolds showed an amorphous profile. The osteoblastic cells viability and proliferation increased in the presence of composites with testosterone over 72 h, and were significantly greater when PLGA/PCL/BCP/T scaffold was tested against PCL/BCP/T. Furthermore alkaline phosphatase production was significantly greater in the same group. In conclusion, the PLGA/PCL/BCP scaffold with testosterone could be a promising option for bone tissue applications due to its biocompatibility and its stimulatory effect on cell proliferation.

Self-assembled organic-inorganic magnetic hybrid adsorbent ferrite based on cyclodextrin nanoparticles.

Organic-inorganic magnetic hybrid materials (MHMs) combine a nonmagnetic and a magnetic component by means of electrostatic interactions or covalent bonds, and notable features can be achieved. Herein, we describe an application of a self-assembled material based on ferrite associated with ß-cyclodextrin (Fe-Ni/Zn/ßCD) at the nanoscale level. This MHM and pure ferrite (Fe-Ni/Zn) were used as an adsorbent system for Cr(3+) and Cr(2)O(7) (2-) ions in aqueous solutions. Prior to the adsorption studies, both ferrites were characterized in order to determine the particle size distribution, morphology and available binding sites on the surface of the materials. Microscopy analysis demonstrated that both ferrites present two different size domains, at the micro- and nanoscale level, with the latter being able to self-assemble into larger particles. Fe-Ni/Zn/ßCD presented smaller particles and a more homogeneous particle size distribution. Higher porosity for this MHM compared to Fe-Ni/Zn was observed by Brunauer-Emmett-Teller isotherms and positron-annihilation-lifetime spectroscopy. Based on the pKa values, potentiometric titrations demonstrated the presence of ßCD in the inorganic matrix, indicating that the lamellar structures verified by transmission electronic microscopy can be associated with ßCD assembled structures. Colloidal stability was inferred as a function of time at different pH values, indicating the sedimentation rate as a function of pH. Zeta potential measurements identified an amphoteric behavior for the Fe-Ni/Zn/ßCD, suggesting its better capability to remove ions (cations and anions) from aqueous solutions compared to that of Fe-Ni/Zn.

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.

Condensation silicones: do new materials really presents better dimensional stability?

The aim of this study was evaluate the dimensional stability of some condensation silicones. The following materials were studied: Coltex/Coltoflax - Coltène, Speedex - Coltène, and Optosil Comfort/Xantopren VL Plus - Kulzer. They were evaluated by dimensional analysis and gas chromatography (GC) performed at the following times: T0, T1, T2, T3, T4, and T5 (immediately after setting, thirty minutes, two hours, twenty four hours, seventy two hours, and seven days after setting, respectively). The dimensional changes were measured directly in the molds using a Mitutoyo microscope. The Coltex fine/Coltoflax and Optosil Comfort/Xantopren VL Plus materials presented dimensional stability for up to thirty minutes after molding, while the Speedex material remained stable for up to two hours after molding. The gas chromatography experiment demonstrated that these materials release ethanol even after clinical setting.

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.

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.

Quercetin/beta-cyclodextrin solid complexes prepared in aqueous solution followed by spray-drying or by physical mixture.

The present study was designed to investigate the influence of operating conditions (temperature, stirring time, and excess amount of quercetin) on the complexation of quercetin with beta-cyclodextrin using a 2(3) factorial design. The highest aqueous solubility of quercetin was reached under the conditions 37 degrees C/24 h/6 mM of quercetin. The stoichiometric ratio (1:1) and the apparent stability constant (Ks = 230 M(-1)) of the quercetin/beta-cyclodextrin complex were determined using phase-solubility diagrams. The semi-industrial production of a 1:1 quercetin/beta-cyclodextrin solid complex was carried out in aqueous solution followed by spray-drying. Although the yield of the spray-drying process was adequate (77%), the solid complex presented low concentration of quercetin (0.14%, w/w) and, thus, low complexation efficiency. The enhancement of aqueous solubility of quercetin using this method was limited to 4.6-fold in the presence of 15 mM of beta-cyclodextrin. Subsequently, an inclusion complex was prepared via physical mixture of quercetin with beta-cyclodextrin (molar ratio of 1:1 and quercetin concentration of 23% (w/w)) and characterized using infrared spectroscopy, differential scanning calorimetry, nuclear magnetic resonance spectroscopy, and scanning electron microscopy analyses. The enhancement of aqueous solubility of quercetin using this method was 2.2-fold, similar to that found in the complex prepared in aqueous solution before the spray-drying process (2.5-fold at a molar ratio of 1:1, i.e., 6 mM of quercetin and 6 mM of beta-cyclodextrin).

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.

Supramolecular self-assembly of cyclodextrin and higher water soluble guest: thermodynamics and topological studies.

The supramolecular interactions between Imipramine hydrochloride (IMI), a tricyclic antidepressant, and beta-cyclodextrin (betaCD) have been investigated by experimental techniques and theoretical calculations. The association between these molecules might be lead to a host/guest compound, in which the physical chemistry properties of the guest molecule, such as high solubility, can be decreased. These new properties acquired by the inclusion phenomena are important to develop a strategy for pharmaceutical formulation. Nuclear magnetic resonance and horizontal attenuated total reflectance provided relevant information on the complex stoichiometries and the sites of interactions between the host and guest molecules. Stoichiometries of 1:2, 1:1, and 2:1 betaCD/IMI have been detected in solution. Self-diffusion coefficient and dynamic light scattering analysis provided information on the self-aggregation of the complex. Also, isothermal titration calorimetry studies indicated the existence of equilibrium between different complexes in solution. In order to determine the preferred arrangement for the inclusion complex formed by the IMI molecule and betaCD, theoretical calculations were performed. Of all proposed supramolecular structures, the 2:1 betaCD/IMI complex was calculated to be the most energetically favorable, in both gas and aqueous phases. The calculations indicated that the intermolecular hydrogen bonds involving the hydroxyl groups of betaCD play a major role in stabilizing the supramolecular 2:1 structure, corroborating experimental findings.

Supramolecular complex of fluoxetine with beta-cyclodextrin: an experimental and theoretical study.

In this work the complex formed between beta-cyclodextrin (betaCD) and fluoxetine (FLU) was investigated by experimental and computational methods. From Horizontal Attenuated Total Reflectance (HATR) was possible to verify a strong modification in the vibrational modes of betaCD and FLU, indicating interactions between them. The Nuclear Magnetic Resonance (NMR) experiments confirm these interactions through the change in chemical shifts in (1)H spectra, reduction in longitudinal relaxation times values, and the Nuclear Ouverhauser Effect confirm the inclusion of aromatic rings of FLU into the betaCD. The structures of the proposed inclusion compounds were optimized at PM3 semiempirical level of theory. In addition, single point calculations at the Density Functional Theory (DFT) level, using the Becke, Lee, Yang, and Parr functional and 6-31G(d,p) basis set, were used to determine the interaction energy for these structures. The DFT calculations identified the aromatic ring, which contains the CF(3) group as the most stable into the betaCD by an amount of, 11.7 kcal mol(-1), in the gas phase. Polarized continuum model, at the DFT level mentioned, was used to investigate the solvent effect, and the results corroborated the gas phase analysis. A high equilibrium constant (K approximately 6921+/-316) and the stoichiometry, 1:1, were obtained by Isothermal Titration Calorimetry (ITC) experiments.