Magnesium (Mg2 +), Strontium (Sr2 +), and Zinc (Zn2 +) Co-substituted Bone Cements Based on Nano-hydroxyapatite/Monetite for Bone Regeneration.

New bone cement type that combines Sr2 + /Mg2 + or Sr2 + /Zn2 + co-substituted nano-hydroxyapatite (n-HAs) with calcium phosphate dibasic and chitosan/gelatin polymers was developed to increase adhesion and cellular response. The cements were physicochemically described and tested in vitro using cell cultures. All cements exhibited quite hydrophilic and had high washout resistance. Cement releases Ca2 + , Mg2 + , Sr2 + , and Zn2 + in concentrations that are suitable for osteoblast proliferation and development. All of the cements stimulated cell proliferation in fibroblasts, endothelial cells, and osteoblasts, were non-cytotoxic, and produced apatite. Cements containing co-substituted n-HAs had excellent cytocompatibility, which improved osteoblast adhesion and cell proliferation. These cements had osteoinductive potential, stimulating extracellular matrix (ECM) mineralization and differentiation of MC3T3-E1 cells by increasing ALP and NO production. The ions Ca2 + , Mg2 + , Zn2 + , and Sr2 + appear to cooperate in promoting osteoblast function. The C3 cement (HA-SrMg5%), which was made up of n-HA co-substituted with 5 mol% Sr and 5 mol% Mg, showed exceptional osteoinductive capacity in terms of bone regeneration, indicating that this new bone cement could be a promising material for bone replacement.

Uniaxial and Coaxial Nanofibers PCL/Alginate or PCL/Gelatine Transport and Release Tamoxifen and Curcumin Affecting the Viability of MCF7 Cell Line.

Breast cancer is the second cause of cancer death in women worldwide. The search for therapeutic and preventive alternatives has increased in recent years. One synthetic drug for patients with hormone receptor-positive tumours is tamoxifen citrate (TMX). Curcumin (Cur) is a natural compound that is being tested. Both were coupled with nanoscale-controlled and sustained release systems to increase the effectiveness of the treatment and reduce adverse effects. We produced a controlled release system based on uniaxial and coaxial polymeric nanofibers of polycaprolactone (PCL), alginate (Alg) and gelatine (Gel) for the transport and release of TMX and Cur, as a new alternative to breast cancer treatment. Nanofibers combining PCL-Alg and PCL-Gel were fabricated by the electrospinning technique and physicochemically characterised by thermal analysis, absorption spectroscopy in the infrared region and X-ray diffraction. Morphology and size were studied by scanning electron microscopy. Additionally, the release profile of TMX and Cur was obtained by UV-Vis spectroscopy. Additionally, the cytotoxic effect on breast cancer cell line MCF7 and peripheral-blood mononuclear cells (PBMCs) from a healthy donor were evaluated by a Resazurin reduction assay. These assays showed that PCL-TMX nanofiber was highly toxic to both cell types, while PCL-Cur was less toxic.

Novel Eudragit® -based polymeric nanoparticles for sustained release of simvastatin

This paper reports on the development of nanoparticles aiming at the in vitro controlled release of simvastatin (SVT). The nanoparticles were prepared by the nanoprecipitation method with polymers Eudragit® FS30D (EDGFS) or Eudragit® NE30D (EDGNE). EDGFS+SVT nanoparticles showed mean size of 148.8 nm and entrapment efficiency of 76.4%, whereas EDGNE+SVT nanoparticles showed mean size of 105.0 nm and entrapment efficiency of 103.2%. Infrared absorption spectra demonstrated that SVT incorporated into the polymer matrix, especially EDGNE. Similarly, the differential scanning calorimeter (DSC) curve presented no endothermic peak of fusion, indicating that the system is amorphous and the drug is not in the crystalline state. The maintenance of SVT in the amorphous state may favors its solubilization in the target release sites. In the in vitro dissolution assay, the SVT incorporated into the EDGFS+SVT nanoparticles showed a rapid initial release, which may be related to the pH of the dissolution medium used. Regarding the EDGNE+SVT nanoparticles, the in vitro release occurred in a bimodal behavior, i.e., an initial "burst" followed by a sustained delivery, with the kinetics of drug release following Baker-Lonsdale's mathematical model. All these features suggest the nanoparticulate system's potential to modulate SVT delivery and enhance its bioavailability.

Angiotensin-(1-7) oral treatment after experimental myocardial infarction leads to downregulation of CXCR4.

Myocardial infarction triggers cellular events that starts with the activation of inflammatory response and fibrogenic pathways involved in cardiac tissue remodeling. Angiotensin-(1-7) (Ang-(1-7)) is an endogenous heptapeptide from the renin-angiotensin system with a cardioprotective role due to its anti-inflammatory and anti-fibrotic activities in cardiac cells. Although the beneficial aspects of Ang-(1-7) in animal models of cardiac ischemia have been reported, the molecular events underlying Ang-(1-7) cardioprotective effect remains elusive. This study investigated the impact of oral treatment with Ang-(1-7) included in hydroxypropyl ß-cyclodextrin (HPßCD/Ang-(1-7)) on the cardiac proteome dysregulation due to experimental myocardial infarction. Wistar male rats were submitted to experimental myocardial infarction and treated daily with HPßCD/Ang-(1-7) during 7 days or 60 days by gavage. Our results showed that HPßCD/Ang-(1-7) treatment ameliorates the post-infarction condition due to the modulation of proteins that initially favor the resolution of inflammation and mitochondrial dysfunction. Moreover, this study reported for the first time that Ang-(1-7) treatment after experimental myocardial infarction leads to the downregulation of the C-X-C chemokine receptor type 4 (CXCR4). SIGNIFICANCE: Myocardial infarction triggers a sequence of cellular and molecular events that starts with an intense inflammatory response that is resolved in the proliferative phase. Prolonged inflammatory phase can lead to adverse cardiac repair and heart failure. In this context, we proposed a post-MI treatment using Ang-(1-7) included in HPßCD and administrated orally. We observed that HPßCD/Ang-(1-7) treatment led to CXCR4 downregulation, highlighting this C-X-C chemokine receptor as a potential therapeutic target for ischemic heart diseases.

Guaiacol/ß-cyclodextrin for rapid healing of dry socket: antibacterial activity, cytotoxicity, and bone repair-an animal study.

PURPOSE: Dry socket (DS) is one the most common and symptomatic post-extraction complications; however, no consensus on its treatment has been reached. This study aimed to develop a novel dressing material for DS containing the phenolic agent guaiacol and evaluate its biological properties. METHODS: An inclusion complex of guaiacol and ß-cyclodextrin (Gu/ßcd) was prepared by freeze-drying. Its antibacterial activity over six oral bacteria was analyzed using the microdilution method, and its cytotoxicity in osteoblasts was assessed with the MTT assay. The alveolar healing process induced by Gu/ßcd was evaluated histologically after the treatment of DS in rats. RESULTS: ßcd complexation potentiated Gu's antibacterial effect and reduced its cytotoxicity in osteoblasts. Bone trabeculae were formed in the alveolar apices of rats treated with Gu/ßcd by day 7. On day 14, woven bone occupied the apical and middle thirds of the sockets; on day 21, the entire alveolus was filled by newly formed bone, which was in a more advanced stage of repair than the positive control (Alvogyl™). CONCLUSION: The improvement in Gu's biological properties in vitro and the rapid alveolar repair in comparison with Alvogyl™ in vivo demonstrated the benefits of the Gu/ßcd complex as a future alternative for the treatment of DS.

Evidence of hypoglycemic, lipid-lowering and hepatoprotective effects of the Bixin and Bixin: ß-CD inclusion compound in high-fat-fed obese mice.

Associations between obesity, diabetes type II, and steatosis have long been recognized. However, a pharmacotherapy that acts in a multifactorial manner controlling the interactions between these conditions is not available. A variety of natural plants, functional fatty acids, and other natural dietary compounds have been used in various anti-obesity products. We investigated the effects of oral administration of an antioxidant carotenoid pigment Bixin and Bixin: ß-Cyclodextrin in an obese murine model. C57BL/6 male mice (4-5 weeks) received standard diet (2.18 kcal per 1 g) (CT) and high-fat diet (4.38 kcal per 1 g) (CT/OB, BIX and BIX/ßCD) (n = 10 per group). After 16 weeks, the BIX and BIX/ßCD were treated by gavage (100 µL day-1) for six weeks, with water (CT and CT/OB groups) and (50 mg kg-1 day-1), Bixin (BIX group) or Bix: ß-CD (BIX/ßCD). Body weight, Lee's Index, adiposity, CHT, TG, CHT/HDL-c, glucose levels (metabolic markers) and, liver markers (AST and ALT) were determined. All metabolic and liver parameters exhibited down-regulation after oral administration of BIX and BIX/ßCD. Particularly relevant was Lee's Index and adiposity in BIX- and BIX/ßCD-treated groups (339.18 g/cm -BIX and 327.58 g/cm -BIX/ßCD vs. 360.68 g/cm -CT/OB animals), this finds associated with the insulin sensitivity test, showed a clear association between reduction of adipose tissue and decrease of peripherical insulin resistant. In conclusion, our study suggested that the oral administration of the Bixin and Bix: ß-CD inclusion compound improved the metabolic parameters evaluate in obese mice, being more palatable and hepatoprotective.

Efficient cutaneous wound healing using bixin-loaded PCL nanofibers in diabetic mice.

The present work demonstrated an efficient cutaneous wound healing using Bixin-loaded polycaprolactone (PCL) nanofibers as a controlled delivery system. The influence of Bixin (Bix) content on PCL nanofiber, Bix-PCL1(2.5% w/w bix) and Bix-PCL2 (12.5% w/w bix) formation was investigated using electrical conductivity, attenuated total reflectance infrared spectroscopy, X-ray diffraction, thermal analysis, and scanning electronic microscopy. The results showed that a greater bixin concentration resulted in higher polymeric solution electrical conductivity. Moreover, higher polymeric solution electrical conductivity provides lower nanofibers in terms of average diameter than pure PCL nanofibers. In vitro release was largely governed by a diffusion-controlled mechanism. The initial Bixin release domain showed a burst release over the first 10 hours where approximately 30% and 40% of Bixin was released from Bix-PCL1 and Bix-PCL2 nanofibers, respectively. The second kinetic domain was comprised of a continuous and slow Bixin release that led to almost 100% of the Bixin being released within 14 days. The results on excisional wound model in induced diabetic mice indicated that the low concentration of Bixin released from loaded Bix-PCL nanofibers maintain the biological activity of Bixin and is efficient in accelerating the wound healing as well as in reducing the scar tissue area compared with pure PCL nanofibers. Therefore, soft material Bixin-loaded PCL nanofibers are a promising candidate for use in wound dressing. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1938-1949, 2017.

Antibacterial Effect of Synthetic Peptide LyeTxI and LyeTxI/ß-Cyclodextrin Association Compound Against Planktonic and Multispecies Biofilms of Periodontal Pathogens.

BACKGROUND: Antimicrobial peptides (AMPs) have shown rapid and potent effect against planktonic bacteria. However, control of periodontopathic biofilms is a challenge even for AMPs. Thus, the present study evaluates in vitro antimicrobial activity of synthetic peptide LyeTxI and association compound LyeTxI/ß-cyclodextrin (ßCD) against multispecies biofilms. METHODS: Sensibility to LyeTxI and LyeTxI/ßCD was determined for planktonic Gram-negative periodontopathogens. Time-kill kinetic assay was performed at minimum inhibitory concentrations (MICs) in all planktonic strains. Multispecies biofilms were grown on pegs using a biofilm device and studied by scanning electron microscopy at 2, 5, and 10 days. Minimal biofilm eradication concentration (MBEC) was determined for 2- and 4-day multispecies biofilms. Metabolic activity of biofilms was determined by fluorometry study. RESULTS: Biofilms showed reproducible cell density on pegs of the biofilm device. LyeTxI and LyeTxI/ßCD were active against all strains tested at concentrations ≤62.5 µg/mL. Kinetic assays showed rapid bactericidal effect of LyeTxI against all periodontopathogens. MBECs of LyeTxI and LyeTxI/ßCD against multispecies 2-day biofilms were two-fold higher than MICs of cells shed from biofilms. LyeTxI was able to reduce multispecies 2-day metabolic activity by 90%. Multispecies 4-day biofilms were tolerant to all agents tested. CONCLUSIONS: LyeTxI and LyeTxI/ßCD are active against periodontopathic bacteria, showing rapid bactericidal effect and may be used to prevent biofilm development. In the future, AMPs could be therapeutic tools for treatment of periodontitis.

Therapeutic uses for Angiotensin-(1-7).

INTRODUCTION: Angiotensin-(1-7) is a key component of the Renin-Angiotensin System, which can counter-regulate several deleterious effects caused by angiotensin II. Due to the potential for therapeutic use, several of its actions are specifically described in patents. AREAS COVERED: In this review, the authors describe a plethora of therapeutic uses for Angiotensin-(1-7), claimed and supported by experimental evidence in patent documents and applications. EXPERT OPINION: The clinical potential of Angiotensin-(1-7) as a therapeutic agent to treat several pathologies is evidenced by the variety of patents and clinical trials involving this peptide. Cancer treatment is one of the most advanced therapeutic areas, but clinical studies are also available in several other areas, such as cardiovascular, hematological, transplantation, surgical and medical procedures.

Development of sulfadiazine-decorated PLGA nanoparticles loaded with 5-fluorouracil and cell viability.

The aim of this work was to synthesize sulfadiazine-poly(lactide-co-glycolide) (SUL-PLGA) nanoparticles (NPs) for the efficient delivery of 5-fluorouracil to cancer cells. The SUL-PLGA conjugation was assessed using FTIR, 1H-NMR, 13C-NMR, elemental analysis and TG and DTA analysis. The SUL-PLGA NPs were characterized using transmission and scanning electron microscopy and dynamic light scattering. Additionally, the zeta potential, drug content, and in vitro 5-FU release were evaluated. We found that for the SUL-PLGA NPs, Dh = 114.0 nm, ZP = -32.1 mV and the encapsulation efficiency was 49%. The 5-FU was released for up to 7 days from the NPs. Cytotoxicity evaluations of 5-FU-loaded NPs (5-FU-SUL-PLGA and 5-FU-PLGA) on two cancer cell lines (Caco-2, A431) and two normal cell lines (fibroblast, osteoblast) were compared. Higher cytotoxicity of 5-FU-SUL-PLGA NPs were found to both cancer cell lines when compared to normal cell lines, demonstrating that the presence of SUL could significantly enhance the cytotoxicity of the 5-FU-SUL-PLGA NPs when compared with 5-FU-PLGA NPs. Thus, the development of 5-FU-SUL-PLGA NPs to cancer cells is a promising strategy for the 5-FU antitumor formulation in the future.

New perspectives for leishmaniasis chemotherapy over current anti-leishmanial drugs: a patent landscape.

INTRODUCTION: Although leishmaniasis is estimated to cause the ninth largest disease burden among individual infectious diseases, it is still one of the most neglected diseases in terms of drug development. Current drugs are highly toxic, resistance is common and compliance of patients to treatment is low, as treatment is long and drug price is high. AREAS COVERED: In this review, the authors carried out a patent landscape in search for new perspectives for leishmaniasis therapy. This search encompassed patent documents having priority date between 1994 and 2014. Selected compounds were compared to current anti-leishmanial drugs regarding efficacy and toxicity, when experimental data were available. EXPERT OPINION: Most patents related to drugs for leishmaniasis have not been produced by the pharmaceutical industry but rather by public research institutes or by universities, and the majority of the inventions disclosed are still in preclinical phase. There is an urgent need to find new ways of funding research for leishmaniasis drugs, incentivizing product development partnerships and pushing forward innovation.

Efficacy of coral-hydroxyapatite and biphasic calcium phosphate for early bacterial detection.

Nano- or microhydroxyapatites with microbiological properties are being used to detect pathogens in clinical samples and industrial environments. In this study, the calcium phosphates coral-hydroxyapatite and biphasic calcium phosphate were characterized physicochemically using x-ray diffraction, thermogravimetric, and differential thermal analysis. The morphology, texture, and chemical composition of the ceramics were also investigated using scanning electron microscopy with energy dispersive spectroscopy. The biocompatibility of the ceramics was evaluated using Escherichia coli and Enterococcus faecalis. Microorganisms were detected by incorporating the enzyme markers 4-metilumbelliferil-ß-d-glucoside and 4-metilumbelliferil-ß-d-glucuronide in the ceramic powders and evaluating fluorescence. The characterization of the ceramics revealed typical characteristics, such as crystallinity, thermal stability, and chemical composition, consistent with other calcium phosphates. The calcium phosphates coral-hydroxyapatite and biphasic calcium phosphate ceramics differed from one another in morphology, structural topography, particle size distribution, and the capacity to absorb water. These properties can influence the rates of microbiological responses and bacterial detection. Although both materials are suitable for use as structural supports in microbial diagnostic systems, BCP was more efficient and detected E. coli and E. faecalis more rapidly than CHA.

Peptides: ß-cyclodextrin inclusion compounds as highly effective antimicrobial and anti-epithelial proliferation agents.

BACKGROUND: The use of antimicrobial peptides (AMPs) as therapeutic agents for periodontal infections has great advantages, such as broad spectrum of action, low toxicity, and limited bacterial resistance. However, their practical use is limited because of the large amount of peptide required to exercise the microbicidal function. METHODS: LyeTxI, LL37f, and KR12 cationic peptides were prepared with ß-cyclodextrin (ßCD) at 1:1 molar ratios. The susceptibility of Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Fusobacterium nucleatum were assessed in anaerobic conditions. Cytotoxicity assays were performed using osteoblast and Caco-2 epithelial cells, and hemolytic activity was assessed on rabbit erythrocytes at an absorbance of 414 nm. Parameters of surface roughness and electrical charge were established by atomic force microscopy and zeta (ζ) potential, respectively. RESULTS: AMP/ßCDs drastically decreased the peptide concentration required for activity against the bacteria tested. Moreover, AMPs associated with ßCD were able to modify cell-surface parameters, such as roughness and ζ potential. On the other hand, AMP/ßCD did not alter the degree of hemolysis induced by the pure AMPs. The effective concentration at half-maximum values of the peptides and compounds on osteoblasts were greater than the concentrations required to achieve inhibition of bacterial growth in all the species tested. AMP/ßCDs inhibited the proliferation of Caco-2 epithelial cells in a more efficient manner than AMPs alone. CONCLUSION: AMP/ßCD compounds more effectively inhibit periodontopathogenic bacteria than AMPs alone, with the additional ability of inhibiting the proliferation of epithelial cells at concentrations that are non-cytotoxic for osteoblasts and erythrocytes.

Evaluation of antimicrobial activity and cell viability of Aloe vera sponges

Background: Aloe vera L., member of the Liliaceae family, has been shown to stimulate cell proliferation and contribute to healing and angiogenesis, has anti-bacterial, anti-fungal and anti-inflammatory activity. In addition, Aloe vera can be used as a support for drug transport. Our objective is to evaluate antimicrobial activity and cytotoxicity of sponges of Aloe vera L. for use as a carrying support of drugs. Results: In this work, sponge of free Aloe vera (AV) loaded with amoxicillin (AMX) or nystatin (NYS) at 1% w/w, were prepared and physico-chemically characterized via X-ray diffraction, Fourier Transform Infrared Spectroscopy and thermal analysis. Antimicrobial potency of AV sponge alone, loaded with AMX or NYS, against strains of Streptococcus mutans, Staphylococcus aureus, Aggregatibacter actinomycetemcomitans, Enterococcus faecalis and Candida albicans was determined. Osteoblasts and human gingival fibroblasts were cultivated on AV, Aloe vera loaded with amoxicillin (AV/AMX) and Aloe vera loaded with nystatin (AV/NYS) and cellular viability was assessed. The physico-chemical characterization performed suggested that the loaded drugs were dispersed in the sponge and those interactions between the AV sponge and the loaded drugs were weak. Furthermore, AV loaded with AMX or NYS demonstrated antimicrobial potency and osteoblasts and fibroblasts were viable after 24 hrs on free AV, and AV loaded with AMX or NYS. Conclusions: Our results indicate that sponges of free AV, loaded with AMX or NYS, are biocompatible and exhibit antimicrobial activity.

Ultrastructural changes in bacterial membranes induced by nano-assemblies ß-cyclodextrin chlorhexidine: SEM, AFM, and TEM evaluation.

Chemical hosts bind their guests by the same physical mechanisms as biomolecules and often display similarly subtle structure activity relationships. The cyclodextrins have found increasing application as inert, nontoxic carriers of active compounds in drug formulations. The present study was conducted to prepare inclusion complexes of chlorhexidine:ß-cyclodextrin (Cx:ß-cd), and evaluate their interactions with bacterial membrane through: scanning electron microscopy (SEM) and transmission electron microscopy (TEM); and measuring morphology alterations, roughness values, and cell weights by atomic force microscopy (AFM). It was found that the antimicrobial activity was significantly enhanced by cyclodextrin encapsulation. SEM analysis images demonstrated recognizable cell membrane structural changes and ultrastructural membrane swelling. By TEM, cellular alterations such as vacuolization, cellular leakage, and membrane defects were observed; these effects were enhanced at 1:3 and 1:4 Cx:ß-cd. In addition, AFM analysis at these ratios showed substantially more membrane disruption and large aggregates mixing with microorganism remains. In conclusion, nanoaggregates formed by cyclodextrin inclusion compounds create cluster-like structures with the cell membrane, possibly due to a hydrogen rich bonding interaction system with increasing surface roughness and possibly increasing the electrostatic interaction between cationic chlorhexidine with the lipopolysaccharides of Gram negative bacteria.

Pharmaceutical composition of hydrochlorothiazide:ß-cyclo-dextrin: preparation by three different methods, physico-chemical characterization and in vivo diuretic activity evaluation.

Hydrochlorothiazide is a common diuretic antihypertensive drug of the thiazide family. Its poor aqueous solubility is one of the reasons for its limited bioavailability after oral administration. This work aimed at the development of a hydrochlorothiazide:ß-cyclodextrin (HTZ:ß-CD) pharmaceutical composition in order to improve water solubility and bioavailability of the drug. The HTZ:ß-CD complexes were prepared by three different methods: spray-drying, freeze-drying and fluid bed. Complexes were characterized by thermal analysis, Fourier transform-infrared (FTIR) spectroscopy, powder X-ray diffractometry, NMR (2D-ROESY), scanning electron microscopy (SEM), particle analysis and intrinsic dissolution. The findings reveal that three binary systems prepared presented better solubility results in comparison with free HTZ. Increased diuretic effect was observed to HTZ:ß-CD obtained by fluid bed in comparison to free drug in rats. Results taken together suggest that pharmacological effect of HTZ in complex was increased by solubility improvement promoted by cyclodextrin.

Daidzein/cyclodextrin/hydrophilic polymer ternary systems.

OBJECTIVE: To evaluate the effect of different cyclodextrins (ß-cyclodextrin [ß-CD], methyl-ß-cyclodextrin [Mß-CD], or hydroxypropyl-ß-cyclodextrin [HPß-CD]) and/or hydrophilic polymers (carboxymethylcellulose, hydroxypropylmethylcellulose [HPMC], polyethyleneglycol, or polyvinylpyrrolidone [PVP]) on daidzein solubility in water. MATERIALS AND METHODS: The corresponding associations were characterized in aqueous media using phase-solubility studies. The morphology of daidzein/cyclodextrin freeze-dried complexes was characterized using scanning electron microscopy, and their spatial configuration was proposed by means of nuclear magnetic resonance spectroscopy. RESULTS AND DISCUSSION: In the presence of 6 mM of cyclodextrins, the solubility of daidzein in water was significantly enhanced: 5.7-fold (ß-CD), 7.2-fold (Mß-CD), and 9.4-fold (HPß-CD). The analysis of the three solid complexes proved that the formation of inclusion complexes occurred through the insertion of the B and C rings of daidzein molecule into the cyclodextrins cavity. The association of daidzein/cyclodextrin complexes to the hydrophilic polymers HPMC or PVP (1%, w/w) was able to improve the solubility of daidzein even further. CONCLUSION: The highest solubilizing effect was obtained for daidzein/HPß-CD/PVP ternary system (12.7-fold).

Pharmaceutical composition of valsartan: beta-cyclodextrin: physico-chemical characterization and anti-hypertensive evaluation.

Valsartan, a water-insoluble drug, is mainly used in the treatment of hypertension albeit with reduced oral bioavailability. The aim of work was to develop a valsartan:beta-cyclodextrin (VAL:beta-CD) pharmaceutical composition in order to improve its water solubility and bioavailability. The VAL:beta-CD complexes were prepared by the kneading, solid dispersion and freeze-drying methods, of which the freeze-drying method (FDY) was found to be the best to prepare an inclusion complex. A physical mixture PM was also prepared. Complexes were characterized by thermal analysis, Fourier transformed-infrared (FTIR) spectroscopy, Powder X-ray diffractometry, intrinsic dissolution and NMR (2D-ROESY). Phase-solubility analysis showed A(L)-type diagrams with beta-cyclodextrin (beta-CD). Microcalorimetric titrations suggested the formation of 1:1 inclusion complex between VAL and beta-CD. The apparent stability constants K(1:1) calculated from phase-solubility plots were 165.4 M(-1) (298 K), 145.0 M(-1) (303 K) and 111.3 M(-1) (310 K). In vivo experiments in rats showed that reduction in arterial pressure for the FDY complex is better than with valsartan used alone. The better activity of FDY can be attributed to the higher solubility of valsartan after inclusion in the cyclodextrin cavity, as suggest by the intrinsic dissolution studies.

Bioceramic/poly (glycolic)-poly (lactic acid) composite induces mineralized barrier after direct capping of rat tooth pulp tissue.

The aim of this study was to observe the histopathological pulp response following direct pulp capping of mechanically exposed teeth in rats with a composite of beta-tricalcium phosphate-hydroxyapatite bioceramic (BC) and poly (glycolic)-poly (lactic acid) (PLGA) material or a calcium hydroxide [Ca(OH)2] material, compared to BC alone and a negative control of water. Pulp of the maxillary molars was exposed, followed by capping with the experimental material. The pulpal tissue response was assessed post-operatively at 1, 7, 14 and 30 d, followed by histological analysis. The Ca(OH)2 group exhibited severe acute inflammatory cell infiltration at day 14. However after 30 d, a new hard tissue with macro porous obliteration of the pulp chamber and a characteristic necrotic area had appeared. BC and Ca(OH)2 capping were associated with moderate inflammation and dentinal bridge similar. Meanwhile, in the BC/PLGA composite group, there was moderate inflammatory infiltrate and formation of a dense and complete dentinal bridge. In conclusion, the BC/PLGA composite material showed a large zone of tertiary dentin, and effectively reorganized the dentin-pulp complex.

Bioceramic/Poly (glycolic)-poly (lactic acid) composite induces mineralized barrier after direct capping of rat tooth pulp tissue

The aim of this study was to observe the histopathological pulp response following direct pulp capping of mechanically exposed teeth in rats with a composite of beta-tricalcium phosphate-hydroxyapatite bioceramic (BC) and poly (glycolic)-poly (lactic acid) (PLGA) material or a calcium hydroxide [Ca(OH)2] material, compared to BC alone and a negative control of water. Pulp of the maxillary molars was exposed, followed by capping with the experimental material. The pulpal tissue response was assessed post-operatively at 1, 7, 14 and 30 d, followed by histological analysis. The Ca(OH)2 group exhibited severe acute inflammatory cell infiltration at day 14. However after 30 d, a new hard tissue with macro porous obliteration of the pulp chamber and a characteristic necrotic area had appeared. BC and Ca(OH)2 capping were associated with moderate inflammation and dentinal bridge similar. Meanwhile, in the BC/PLGA composite group, there was moderate inflammatory infiltrate and formation of a dense and complete dentinal bridge. In conclusion, the BC/PLGA composite material showed a large zone of tertiary dentin, and effectively reorganized the dentin-pulp complex.