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The drug rapamycin is a potent inhibitor of the mTOR complex, acting directly in the signaling cascade of this protein complex; interrupting cell proliferation, in addition to being an extremely efficient immunosuppressant. Currently this drug is being used in several types of cancer. Rapamycin has been a target of great interest within nanomedicine involving nanostructured systems for drug delivery aiming to increase the bioactivity and bioavailability of this drug. In addition, there is a constant search for analytical methods to identify and quantify this drug. Numerous high-performance liquid chromatography analytical techniques, mass spectrometry and immunoassay techniques have been employed efficiently in an attempt to develop increasingly sensitive analytical methods. Thus, this review sought to bring together current and relevant scientific works involving rapamycin and; besides analytical methods more used for quantification of this molecule.
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BACKGROUND: Vulvovaginal candidiasis (VVC) is a worldwide public health problem caused predominantly by the opportunistic polymorphic fungus Candida albicans, whose pathogenicity is associated with its morphological adaptability. To potentiate the treatment of C. albicans-induced VVC by an alternative method as photodynamic therapy (PDT), hypericin (Hy), a potent photosensitizer compound was incorporated into a nanostructured lipid carrier (NLC) and dispersed in hydrogel (HG). METHODS: After preparation of the sonication process, an NLC loaded with Hy was dispersed in HG based on Poloxamer 407 and chitosan obtaining Hy.NLC-HG. This hydrogel system was physically and chemically characterized and its in vitro and in vivo photodynamic and antifungal effects were evaluated. RESULTS: Through scanning electron microscopy, it was possible to observe a hydrogel system with a porous polymeric matrix and irregular microcavities. The Hy.NLC-HG system showed mucoadhesive properties (0.45 ± 0.08 N) and a satisfactory injectability (15.74 ± 4.75 N.mm), which indicates that it can be easily applied in the vaginal canal, in addition to a controlled and sustained Hy release profile from the NLC-HG of 28.55 ± 0.15% after 720 min. The in vitro antibiofilm assay significantly reduced the viability of C. albicans (p < 0.001) by 1.2 log10 for Hy.NLC-HG/PDT and 1.9 log10 for PS/PDT, Hy.NLC/PDT, and free RB/PDT, compared to the PBS/PDT negative control. The in vivo antifungal evaluation showed that animals treated with the vaginal cream (non-PDT) and the PDT-mediated Hy.NLC-HG system showed a significant difference of p < 0.001 in the number of C. albicans colonies (log) in the vaginal canal, compared to the inoculation control group. CONCLUSIONS: Thus, we demonstrate the pharmaceutical, antifungal, and photodynamic potential of hydrogel systems for Hy vaginal administration.
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Curcumin has great potential as a photosensitizer, but it has low solubility in aqueous solutions. This study reports the antimicrobial efficacy of photodynamic inactivation (PDI) mediated by a curcumin-loaded liquid crystal precursor (LCP) on in situ dental biofilms. Thirty volunteers used intraoral devices containing enamel samples for 48 hours for biofilm formation. The samples were then removed from the device and treated either with LCP with 160 µM of curcumin plus illumination at 18 J/cm2 (C + L+ group) or with LCP without curcumin in the dark (C - L - group). Following this, the biofilm from the samples was plated for quantifying the viable colonies at 37°C for 48 hours. Specific and nonspecific media were used for the presumptive isolation of Streptococcus mutans, Lactobacillus species/aciduric microorganisms, Candida species, and total microbiota. The C + L+ group showed a highly significant (P < .001) reduction in the log10 (colony forming units/mL) values as compared to the C - L - group for all culture media. Hierarchical linear regression indicated that there may be predictors at individual volunteer level explaining the difference in the PDI efficacy among different individuals (P = .001). The LCP system retained curcumin and released it slowly and continuously, thus protecting the drug from photodegradation. LCP with curcumin is considered effective for the photoinactivation of dental biofilms, but the PDI efficacy may differ based on the host's individual characteristics.
Assuntos
Curcumina , Cristais Líquidos , Fotoquimioterapia , Humanos , Curcumina/farmacologia , Fármacos Fotossensibilizantes/farmacologia , BiofilmesRESUMO
Piperine is an alkaloid mostly found in the fruits of several species of the Piper genus, and its anti-inflammatory potential is already known. However, its therapeutic applications still need to be better explored due to the low aqueous solubility of this active. To overcome this drawback, the objective of this work was to evaluate the efficiency of the nanoencapsulation of the compound as well as its incorporation into hyaluronic acid/alginate-based biomembranes. Polymeric nanoparticles composed of Eudragit S100 and Poloxamer 188 were obtained by the nanoprecipitation technique, obtaining spherical nanosized particles with an average diameter of 122.1 ± 2.0 nm, polydispersity index of 0.266, and encapsulation efficiency of 76.2 %. Hyaluronic acid/sodium alginate membranes were then prepared and characterized. Regarding permeation, a slow passage rate was observed until the initial 14 h, when an exponential increase in the recovered drug concentration began to occur. The in vivo assay showed a reduction in inflammation up to 43.6 %, and no cytotoxicity was observed. The results suggested the potential of the system developed for the treatment of inflammatory skin diseases.
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Alcaloides , Dermatite , Nanopartículas , Humanos , Ácido Hialurônico , Alginatos , Alcaloides/farmacologia , Tamanho da PartículaRESUMO
Abstract Solid dispersions (SDs) of ursolic acid (UA) were developed using polyvinylpyrrolidone K30 (PVP K30) in combination with non-ionic surfactants, such as D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) or poloxamer 407 (P407) with the aim of enhancing solubility and in vitro release of the UA. SDs were investigated using a 24 full factorial design, subsequently the selected formulations were characterized for water solubility, X-ray diffractometry (XRD), differential scanning calorimetry (DSC), particle diameter, scanning electron microscopy, drug content, physical-chemical stability and in vitro release profile. SDs showed higher UA water-solubility than physical mixtures (PMs), which was attributed by transition of the drug from crystalline to amorphous or molecular state in the SDs, as indicated by XRD and DSC analyses. SD1 (with P407) and SD2 (with TPGS) were chosen for further investigation because they had higher drug load. SD1 proved to be more stable than SD2, revealing that P407 contributed to ensure the stability of the UA. Furthermore, SD1 and SD2 increased UA release by diffusion and swelling-controlled transport, following the Weibull model. Thus, solid dispersions obtained with PVP k-30 and P407 proved to be advantageous to enhance aqueous solubility and stability of UA.
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Polietilenoglicóis/administração & dosagem , Solubilidade , Poloxâmero/efeitos adversos , Difusão , Raios X/efeitos adversos , Técnicas In Vitro , Varredura Diferencial de Calorimetria/métodos , Preparações Farmacêuticas/análise , Microscopia Eletrônica de Varredura/métodosRESUMO
Since 1966, rifampicin (RIF) has been considered one of the most potent drugs in the treatment of tuberculosis (TB), which is caused by infection with M. tuberculosis (Mtb). New nanostructured formulations for RIF delivery and alternative routes of administration have been studied as potential forms of treatment. This study evaluates a liquid crystal system for RIF delivery, using alternative drug delivery routes. The systems developed are composed of surfactant, oleylamine, and soy phosphatidylcholine. With the aid of polarized light microscopy, it was possible to determine that the developed systems had a hexagonal mesophase. All systems developed showed non-Newtonian pseudoplasticity and a high degree of thixotropy. Liquid crystal systems with RIF showed an increase in elastic potential, indicating greater mu-coadhesiveness. The evaluation of mucoadhesive forces revealed an increase in the mucoadhesive potential in the presence of mucus, indicating the presence of satisfactory mucoadhesive forces. The 9DR and 10DR liquid crystal systems, when submitted to Differential Scanning Calorimetry analysis, remained structured even at temperatures above 100 °C, showing excellent stability. The developed liquid crystal systems showed a tolerable degree of cytotoxicity and bactericidal potential, for example, the 9DR system demonstrated a reduction in bacterial load after the third day and reached zero CFU on the seventh day of the test. The developed systems were also evaluated in the preclinical model of Mtb-infected mice, using the nasal, sublingual, and cutaneous route for the delivery of RIF associated with a nanostructured liquid crystal system as a possible tool in the treatment of TB.
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Trans-resveratrol can promote various dermatological effects. However, its high crystallinity decreases its solubility and bioavailability. Therefore, solid dispersions have been developed to promote its amorphization; even so, they present as powders, making cutaneous controlled drug delivery unfeasible and an alternative necessary for their incorporation into other systems. Thus, polyvinylpyrrolidone (PVP) films were chosen with the aim of developing a controlled delivery system to treat inflammation and bacterial infections associated with atopic dermatitis. Four formulations were developed: two with solid dispersions (and trans-resveratrol) and two as controls. The films presented with uniformity, as well as bioadhesive and good barrier properties. X-ray diffraction showed that trans-resveratrol did not recrystallize. Fourier-transform infrared spectroscopy (FT-IR) and thermal analysis evidenced good chemical compatibilities. The in vitro release assay showed release values from 82.27 ± 2.60 to 92.81 ± 2.50% (being a prolonged release). In the in vitro retention assay, trans-resveratrol was retained in the skin, over 24 h, from 42.88 to 53.28%. They also had low cytotoxicity over fibroblasts. The in vivo assay showed a reduction in inflammation up to 66%. The films also avoided Staphylococcus aureus's growth, which worsens atopic dermatitis. According to the results, the developed system is suitable for drug delivery and capable of simultaneously treating inflammation and infections related to atopic dermatitis.
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The drug rapamycin is a potent inhibitor of the mTOR complex, acting directly in the signaling cascade of this protein complex; interrupting cell proliferation, in addition to being an extremely efficient immunosuppressant. Currently this drug is being used in several types of cancer. Rapamycin has been a target of great interest within nanomedicine involving nanostructured systems for drug delivery aiming to increase the bioactivity and bioavailability of this drug. In addition, there is a constant search for analytical methods to identify and quantify this drug. Numerous high-performance liquid chromatography analytical techniques, mass spectrometry and immunoassay techniques have been employed efficiently in an attempt to develop increasingly sensitive analytical methods. Thus, this review sought to bring together current and relevant scientific works involving rapamycin and; besides analytical methods more used for quantification of this molecule.
Assuntos
Neoplasias , Sirolimo , Humanos , Espectrometria de Massas , Preparações Farmacêuticas , Transdução de Sinais , Sirolimo/química , Sirolimo/farmacologiaRESUMO
The present study reports the performance of the pigment hypericin (HYP)-loaded poloxamer-based mucoadhesive in situ gelling liquid crystalline precursor system (LCPS) for the treatment of vulvovaginal candidiasis (VVC) in mice. LCPS composed of 40% of ethoxylated and propoxylated cetyl alcohol, 30% of oleic acid and cholesterol (7:1), 30% of a dispersion of 16% poloxamer 407 and 0.05% of HYP (HYP-LCPS) was prepared and characterized by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS) and ex vivo permeation and retention studies across vaginal porcine mucosa were performed. In addition, the antifungal properties of the HYP-LCPS were evaluated in a murine in vivo model; for this, infected C57BL female mice groups were treated with both HYP in solution and HYP-LCPS, and after 6 days colony forming unit (CFU)/ml count was performed. PLM and SAXS confirmed that HYP-LCPS is a microemulsion situated in boundary transition region confirming its action as an LCPS. When in contact with simulated vaginal fluid, HYP-LCPS became rigid and exhibited maltase crosses and bragg peaks characteristics of lamellar phase. Ex vivo permeation and retention studies showed that HYP-LCPS provides a localized treatment on the superficial layers of porcine vaginal mucosa. HYP-LCPS induced a significant reduction in the number of CFU/ml in the mice; thus this formulation indicated it is as effective as a commercial dosage form. It was concluded that LCPS maintains the biological activity of HYP and provides an adequate drug delivery system for this lipophilic molecule at the vaginal mucosa, being a promising option in cases of VVC.
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Antracenos/administração & dosagem , Antifúngicos/administração & dosagem , Candida albicans/efeitos dos fármacos , Candidíase Vulvovaginal/tratamento farmacológico , Perileno/análogos & derivados , Vagina/metabolismo , Adesivos/administração & dosagem , Animais , Antracenos/metabolismo , Antifúngicos/metabolismo , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia de Polarização , Mucosa/metabolismo , Mucosa/microbiologia , Mucosa/patologia , Perileno/administração & dosagem , Perileno/metabolismo , Poloxâmero/administração & dosagem , Radiossensibilizantes , Espalhamento a Baixo Ângulo , Suínos , Vagina/microbiologia , Vagina/patologia , Difração de Raios XRESUMO
BACKGROUND: Vaginal infections caused by non-albicans species have become common in women of all age groups. The resistance of species such as Candida parapsilosis to the various antifungal agents is a risk factor attributed to these types of infections, which instigates the search for new sources of active compounds in vulvovaginal candidiasis (VCC) therapy. OBJECTIVE: This study evaluated the antifungal activity of Syngonanthus nitens Bong. (Ruhland) derivatives and employed a lipid nanoemulsion as a delivery system.' METHODS: In this study, a lipid nanoemulsion was employed as a delivery system composed of Cholesterol (10%), soybean phosphatidylcholine: Brij 58 (1: 2) and PBS (pH 7.4) with the addition of 0.5% of a chitosan dispersion (80%), and evaluated the antifungal activity of S. nitens Bong. (Ruhland) derivatives against planktonic cells and biofilms of Candida parapsilosis. By a biomonitoring fractionation, the crude extract (EXT) and one fraction (F2) were selected and incorporated into a lipid nanoemulsion (NL) composed of cholesterol (10%), a 1:2 mixture of soybean phosphatidylcholine:polyoxyethylene -20- cetyl ether (10%), and phosphate buffer solution (pH 7.4) with a 0.5% chitosan dispersion (80%). The NL presented a diameter size between 50-200 nm, pseudoplastic behavior, and positive charge. The EXT and five fractions were active against planktonic cells. RESULTS AND DISCUSSION: The incorporation of EXT and F2 into the NL increased antifungal activity and enhanced the anti-biofilm potential. This study classified the use of an NL as an important tool for the administration of S. nitens derivatives in cases of infections caused by this C. parapsisilosis. CONCLUSION: This work concluded that S. nitens derivatives were important sources of active molecules against C. parapsilosis and the use of a lipid nanoemulsion was an important tool to promote more effective F2 release and to improve the antifungal activity aiming the control of C. parapsilosis infections.