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Made available in DSpace on 2022-05-01T06:02:36Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-09-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Background: Although Curcumin (CUR) has great potential as a photosensitizer, the low solubility in water impairs its clinical performance in photodynamic inactivation (PDI). This study sought to establish an effective antimicrobial protocol for PDI using CUR in three different bioadhesive formulations. Methods: A CUR-loaded chitosan hydrogel with a poloxamer (CUR-CHIH), a CUR-loaded liquid crystal precursor system (CUR-LCP), a CUR-loaded microemulsion (CUR-ME), and CUR in dimethylsulfoxide (DMSO) solution (CUR-S; control formulation) were tested against in vitro and in situ oral biofilms. The optical properties of each formulation were evaluated. Results: All of the formulations exhibited lower absorbance than CUR-S; however, the CUR-LCP curve bore the highest resemblance. The CUR present in all formulations was completely degraded after 15 min of illumination. In vitro experiments showed that CUR-S was the only formulation able to significantly reduce biofilm viability of Candida albicans and Lactobacillus casei when compared to the negative control (no PDI); the amount of reduction obtained was 1.8 and 3.7 log (CFU/mL) for C. albicans and L. casei, respectively. There was a significant reduction on the viability of Streptococcus mutans biofilms when CUR-S and CUR-LCP were applied (approximately 3.5 and 1.6 log [CFU/mL], respectively). In situ testing showed antimicrobial efficacy against S. mutans and general microorganisms. Conclusions: Although the evaluated protocols has not been effective to all of the evaluated microorganisms, PDI showed potential against dental biofilms and evidence that the phototoxic effects of CUR have a high relation with the type of formulation in which it is loaded. Independent researcher at the moment of the submission (unaffiliated researcher) Department of Social Dentistry School of Dentistry UNESP - São Paulo State University Department of Clinical Analysis School of Pharmacy UNESP - São Paulo State University Department of Biosciences Piracicaba Dental School UNICAMP University of Campinas Department of Drugs and Pharmaceutics School of Pharmacy UNESP - São Paulo State University Department of Social Dentistry School of Dentistry UNESP - São Paulo State University Department of Clinical Analysis School of Pharmacy UNESP - São Paulo State University Department of Drugs and Pharmaceutics School of Pharmacy UNESP - São Paulo State University FAPESP: 2013/15770-6 FAPESP: 2015/24112-8

Curcumin-mediated Photodynamic Inactivation (PDI) has shown great potential to disinfect specific sites on tooth enamel but may involve contact with restorative materials. Thus, before use in dentistry, it is necessary to investigate whether the PDI protocol causes undesirable changes in the surfaces of aesthetic restorative materials and dental enamel. This study investigated the effect of PDI mediated by curcumin (CUR) in a liquid crystal precursor system on color stability (ΔE), surface roughness (Ra), and microhardness (kgf) of three different composite resins and bovine dental enamel specimens. The microhardness and roughness readings were performed 60 days after the treatments while the color readings were performed immediately, 24, 48, and 72 h, 7, 14, 21, 30, and 60 days after the treatments. Results showed that CUR mediated-PDI does not seem to have the potential to promote any esthetic or mechanical changes to the surface of tooth enamel and can be applied safely in clinical practice. However, the results on color, roughness, and hardness obtained for composite resins show that some negative effects can be produced, depending on the type of restorative material, more experiments must be performed with different formulations and, perhaps, with lower concentrations of CUR.

Recent advances have been reported for needle-free local anesthesia in maxillary teeth by administering a nasal spray of tetracaine (TTC) and oxymetazoline, without causing pain, fear, and stress. This work aimed to assess whether a TTC-loaded hybrid system could reduce cytotoxicity, promote sustained permeation, and increase the anesthetic efficacy of TTC for safe, effective, painless, and prolonged analgesia of the maxillary teeth in dental procedures. The hybrid system based on TTC (4%) encapsulated in nanostructured lipid carriers (NLC) and incorporated into a thermoreversible hydrogel of poloxamer 407 (TTCNLC-HG4%) displayed desirable rheological, mechanical, and mucoadhesive properties for topical application in the nasal cavity. Compared to control formulations, the use of TTCNLC-HG4% slowed in vitro permeation of the anesthetic across the nasal mucosa, maintained cytotoxicity against neuroblastoma cells, and provided a three-fold increase in analgesia duration, as observed using the tail-flick test in mice. The results obtained here open up perspectives for future clinical evaluation of the thermoreversible hybrid hydrogel, which contains TTC-loaded NLC, with the aim of creating an effective, topical, intranasal, needle-free anesthesia for use in dentistry.

Made available in DSpace on 2022-05-01T08:44:42Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-08-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) 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. São Paulo State University (UNESP) School of Pharmaceutical Sciences, Araraquara Department of Biosciences Piracicaba Dental School University of Campinas - UNICAMP, Piracicaba Paraíba State University Campina Grande São Paulo State University (UNESP) School of Pharmaceutical Sciences, Araraquara FAPESP: 16/11198-4 FAPESP: 2019/10261-2

Made available in DSpace on 2021-06-25T10:55:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-04-01. Added 1 bitstream(s) on 2021-07-15T15:05:25Z : No. of bitstreams: 1 S0103-50532021000400786.pdf: 944248 bytes, checksum: 167925933dc0ec4ec63ea2afbf080153 (MD5) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Platonia insignis fruit, popularly known as bacuri, is traditionally used in folk medicine for its anti-inflammatory and antioxidant properties. Therefore, this study determined the chemical composition and biological activities of the bacuri’s shell and seeds extracts, considered residues from its consumption and industrial uses. Four biflavonoids (GB-2a, GB-1a, morelloflavone, and volkensiflavone) were identified in the extracts by high-performance liquid chromatography-diode array detection (HPLC-DAD), liquid chromatography tandem mass spectrometry (LC-MS/MS), and liquid chromatography-solid phase extraction-nuclear magnetic resonance (LC-SPE-NMR) techniques. Morelloflavone was identified as the main compound in the shell ethyl acetate extract, being responsible for the high in vitro antioxidant (50% effective concentration (EC50) ranging from 8.0-10.5 µg mL−1 in different protocols), anti-glycant (80%), and moderate inhibition of nitric oxide (1.56 µg mL−1 for > 90% cell viability) activities. This extract showed promising in vivo anti-inflammatory activity evaluated through the paw edema protocol after its incorporation into a liquid-crystalline drug carrier system, reducing the edema by up to 31%. The results demonstrated the potential of the fruit for the development of drugs of natural origin and corroborated to add economic value to these discarded residues. Núcleo de Bioensaios Biossíntese e Ecofisiologia de Produtos Naturais (NuBBE) Departamento de Química Orgânica Instituto de Química Universidade Estadual Paulista “Júlio de Mesquita Filho” (Unesp) Departamento de Fármacos e Medicamentos Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista “Júlio de Mesquita Filho” (Unesp) Laboratório de Fitoquímica e Biomoléculas (LabFitoBio) Departamento de Química Universidade Estadual de Londrina (UEL) Faculdade de Ciências Exatas e Tecnologia (FACET) Universidade Federal da Grande Dourados (UFGD) Departamento de Genética e Morfologia Universidade de Brasília (UnB) Departamento de Ciências Biológicas Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista “Júlio de Mesquita Filho” (Unesp) Núcleo de Bioensaios Biossíntese e Ecofisiologia de Produtos Naturais (NuBBE) Departamento de Química Orgânica Instituto de Química Universidade Estadual Paulista “Júlio de Mesquita Filho” (Unesp) Departamento de Fármacos e Medicamentos Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista “Júlio de Mesquita Filho” (Unesp) Departamento de Ciências Biológicas Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista “Júlio de Mesquita Filho” (Unesp) CNPq: 142014/2018-4 CNPq: 159735/2017-3 FAPESP: 2013/07600-3 CNPq: 2014/465637-0 FAPESP: 2014/50926-0 FAPESP: 2016/16970-7 FAPESP: 2017/18807-9 FAPESP: 2017/19870-6

Made available in DSpace on 2021-06-25T15:00:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-03-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Cervical cancer is the fourth most common cancer in women. Conventional treatments involve surgery, radiotherapy and radiochemotherapy, which affect negatively the life quality. Bioactive molecules, such as curcumin (CUR), are potential alternatives for cervical cancer treatment. However, CUR has limited solubility in water, thus it is interesting to develop drug delivery systems to improve its clinical use. Here, we propose a liquid crystalline system (LCS) as a medium for the formulation and vaginal administration of CUR. To the best of our knowledge, this is the first study that showed the effect of vaginal mucus on the behavior of the liquid crystalline system as well as the antiangiogenic effect of curcumin incorporated in this system in the CAM model. We formulated LCS based on oleic acid, ethoxylated and propoxylated cetyl alcohol and aqueous phase containing water (FW) or dispersion of chitosan associated with polyethyleneimine (FPC). The characterization methodology revealed that LCS presented a lamellar mesophase, which remained stable in the presence of CUR and artificial vaginal mucus. Rheological, texture, and mucoadhesive tests showed that FPC demonstrated properties desirable for vaginal formulations. In vitro release and ex vivo permeation and retention validated the controlled-release properties of the system. LCS released approximately twice as much CUR as the control in 12 h, while ex-vivo porcine vaginal mucosa retained about 2.3% of CUR from LCS.These formulations revealed biocompatibility for L929 cells and toxicity for Hela cells. The vascular changes in response to this potential treatment were evaluated using the chick embryo chorioallantoic membrane (CAM) as a model. The caliber and the number of vessels reduced after the application of CUR-loaded formulations, encouraging the application of the mucoadhesive LCS developed for cervical cancer treatment. (C) 2020 Elsevier B.V. All rights reserved. Sao Paulo State Univ, Sch Pharmaceut Sci, Dept Drugs & Med, BR-01049010 Araraquara, SP, Brazil Univ Estadual Campinas, Piracicaba Dent Sch, Dept Biosci, BR-13414903 Piracicaba, SP, Brazil Univ Sao Paulo, Sao Carlos Inst Phys, BR-13560970 Sao Carlos, SP, Brazil Sao Paulo State Univ, Sch Pharmaceut Sci, Dept Drugs & Med, BR-01049010 Araraquara, SP, Brazil FAPESP: 2017/23357-2 FAPESP: 2019/07245-5 FAPESP: 2018/234304 FAPESP: 2016/14033-6

Made available in DSpace on 2021-06-25T12:42:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-02-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Programa de Apoio ao Desenvolvimento Cientifico (PADC) Current researches report an actual benefit of a treatment for oral cancer via inhibition of proteolytic matrix metalloproteinases (MPP) with a peptide drug, called CTT1. However, peptides present poor oral bioavailability. Topical administration on oral mucosa avoids its passage through the gastrointestinal tract and the first-pass liver metabolism, but the barrier function of the oral mucosa can impair the permeation and retention of CTT1. The objective of this study is to incorporate CTT1 into a mucoadhesive precursor of liquid crystalline system (PLCS) as an interesting strategy for the topical treatment of oral cancer. PLCS consisting of oleic acid, ethoxylated 20 and propoxylated cetyl alcohol 5, polyethyleneimine (P)-associated chitosan (C) dispersion and CTT1 (FPC-CTT1) was developed and characterized by polarized light microscopy (PLM) and small-angle X-ray scattering (SAXS). In vitro permeation and retention across esophageal mucosa, in vitro cytotoxicity towards tongue squamous cell carcinoma cells, and in vivo evaluation of vascular changes using the chick embryo chorioallantoic membrane (CAM) model were performed. PLM and SAXS showed that FPC-CTT1acted as PLCS, because it formed a lamellar liquid crystalline system after the addition of artificial saliva. FPC-CTT1increased approximately 2-fold the flux of permeation and 3- fold the retention of CTT1 on the porcine esophageal mucosa. CTT1 does not affect cell viability. CAM tests showed that FPC preserved the blood vessels and it can be a safe formulation. These findings encourage the use of the FPC-CTT1 for topical treatment of oral cancer. Univ Estadual Campinas, UNICAMP, Piracicaba Dent Sch Dept Biosci, BR-13414903 Piracicaba, SP, Brazil Sao Paulo State Univ, Sch Pharmaceut Sci, Dept Drugs & Med, UNESP, BR-14800903 Araraquara, SP, Brazil Univ Minho, Life & Hlth Sci Res Inst ICVS, Sch Hlth Sci, P-4710057 Braga, Portugal ICVS 3Bs PT Govt Associate Lab, P-4710057 Braga, Portugal Sao Paulo State Univ, Sch Pharmaceut Sci, Dept Drugs & Med, UNESP, BR-14800903 Araraquara, SP, Brazil FAPESP: 13/015651 FAPESP: 16/06337-5 FAPESP: 19/07245-5 FAPESP: 2014/50928-2 CNPq: 465687/2014-8

Made available in DSpace on 2020-12-12T02:13:05Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-08-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Cancer represents a significant public health problem. More than 18.1 million people are annually diagnosed with cancer and 9.6 million die mainly due to metastatic disease. Chemotherapy has been one of the main cancer treatment modalities; however, most of the chemotherapeutic agents are non-specific, exhibiting several toxic side effects, which compromises the patient's quality of life. Therefore, it is necessary to search for new therapeutic alternatives, using for example, drug delivery systems (DDS) to target cancer cells, increasing the selectivity of chemotherapeutic drugs. This approach is promising; however, it is crucial to evaluate the biological performance of the systems. Although mammalian models continue to be explored for clinical applications, they are time-consuming and very restrictive from the ethical and legal perspectives. Hence, the chick embryo chorioallantoic membrane (CAM) has been shown to be a suitable in vivo model since it allows a more appropriate model for the study of drugs and/or DDS performance than in vitro tests. Thereby, this article revises the recent advances of DDS for cancer therapy, evaluating the feasibility of the CAM model. UNESP São Paulo State University School of Pharmaceutical Sciences Department of Drugs and Medicines UNESP São Paulo State University School of Pharmaceutical Sciences Department of Clinical Analysis Life and Health Sciences Research Institute (ICVS) School of Medicine University of Minho ICVS/3B's-PT Government Associate Laboratory UNICAMP University of Campinas Piracicaba Dental School Department of Biosciences UNESP São Paulo State University School of Pharmaceutical Sciences Department of Drugs and Medicines UNESP São Paulo State University School of Pharmaceutical Sciences Department of Clinical Analysis FAPESP: #2013/01565-1 FAPESP: #2015/21412-0 FAPESP: #2016/06337-5, #2019/07245-5 FAPESP: #2016/09671-3 FAPESP: #2017/10016-2 FAPESP: #2017/23357-2 FAPESP: #2018/04546-1

Kelly Limi Aida,1 Paula Fernanda Kreling,1 Karina Sampaio Caiaffa,2 Giovana Maria Fioramonti Calixto,3 Marlus Chorilli,3 Denise MP Spolidorio,4 Norival Alves Santos-Filho,5,6 Eduardo Maffud Cilli,5 Cristiane Duque1 1Department of Pediatric Dentistry and Public Health, Araçatuba Dental School, Sao Paulo State University (UNESP), Araçatuba, São Paulo, Brazil; 2Department of Endodontics, Araçatuba Dental School, Sao Paulo State University (UNESP), Araçatuba, São Paulo, Brazil; 3Department of Drugs and Medicines, School of Pharmaceutical Sciences, Sao Paulo State University (UNESP), Araraquara, São Paulo, Brazil; 4Department of Physiology and Pathology, Araraquara Dental School, Sao Paulo State University (UNESP), Araraquara, São Paulo, Brazil; 5Department of Biochemistry and Chemical Technology, Institute of Chemistry, Sao Paulo State University (UNESP), Araraquara, São Paulo, Brazil; 6Registro Experimental Campus, Sao Paulo State University (UNESP), Registro, São Paulo, Brazil Background: Anticaries agents must interfere with the adhesion of Streptococcus mutans and its proliferation in dental biofilm, without causing host toxicity and bacterial resistance. Natural substances, including cationic antimicrobial peptides (CAMPs) and their fragments, such as β-defensin-3 peptide fragment (D1–23), have been widely studied. However, the chemical and physical stability of CAMPs may be compromised by external factors, such as temperature and pH, reducing the period of antimicrobial activity. Methods: To overcome the aforementioned disadvantage, this study developed and characterized a drug delivery system and evaluated the cytotoxicity and effect against S. mutans biofilm of a D1–23-loaded bioadhesive liquid crystalline system (LCS). LCS was composed of oleic acid, polyoxypropylene-(5)-polyoxyethylene-(20)-cetyl alcohol, Carbopol® 974P and Carbopol® 971P. LCS was analyzed by polarized light microscopy (PLM), rheology (viscoelasticity and flow properties) and in vitro bioadhesion. The viability of epithelial cells was evaluated. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) against S. mutans were determined for D1–23 for further evaluation of the effect against S. mutans biofilm after 4 and 24h of exposure to treatments. Results: PLM, rheology, and in vitro bioadhesion tests showed that both viscosity and bioadhesion of LCS increased after it was diluted with artificial saliva. D1–23-loaded LCS system presented better activity against S. mutans biofilm after 24h when compared to 4h of treatment, showing a cumulative effect. Neither LCS nor D1–23-loaded LCS presented toxicity on human epithelial cells. Conclusion: D1–23-loaded LCS is a promising drug delivery system for the prevention of dental caries. Keywords: peptide fragments, drug delivery system, dental caries, biofilm, Streptococcus mutans

Staphylococcus aureus is a common gram-positive bacterium of the human skin microbiota. It is also a dangerous pathogen that can cause serious and even lethal skin infections. The topical administration of metronidazole via nanotechnology-based drug delivery systems, such as liquid crystalline systems, can modulate both the drug permeation and activity, decreasing its side effects and increasing the drug potent activity against the gram-positive bacteria. This study aimed at: (1) structurally developing and characterizing a liquid crystalline systems composed of chitosan and polyethyleneimine dispersion as the aqueous phase, oleic acid as the oily phase, and ethoxylated and propoxylated cetyl alcohol as the surfactant (FPC) for metronidazole incorporation (0.5% w/w); (2) evaluating the in vitro release and skin permeation and retention properties of the metronidazole-loaded liquid crystalline systems (FPC-M); (3) investigating the in vitro antibacterial activity of FPC-M against Staphylococcus aureus. Polarised light microscopy indicated that both FPC and FPC-M are hexagonal systems. Rheological, texture, and bioadhesion assays showed that both are elastic and bioadhesive systems. According to the results of the in vitro release, permeation, and retention assays, FPC can modulate metronidazole release and allow metronidazole to stay for a longer time on the skin. The determination of FPC-M activity against Staphylococcus aureus showed that it could target the bacterial cell. In conclusion, the liquid crystalline systems developed in this study can improve the clinical performance of metronidazole in the treatment of staphylococcal skin infections.

Formation of a dental biofilm by Streptococcus mutans can cause dental caries, and remains a costly health problem worldwide. Recently, there has been a growing interest in the use of peptidic drugs, such as peptide p1025, analogous to the fragments 1025-1044 of S. mutans cellular adhesin, responsible for the adhesion and formation of dental biofilm. However, peptides have physicochemical characteristics that may affect their biological action, limiting their clinical performance. Therefore, drug-delivery systems, such as a bioadhesive liquid-crystalline system (LCS), may be attractive strategies for peptide delivery. Potentiation of the action of LCS can be achieved with the use of bioadhesive polymers to prolong their residence on the teeth. In line with this, three formulations - polyoxypropylene-(5)-polyoxyethylene-(20)-cetyl alcohol, oleic acid, and Carbopol C974P in different combinations (F1C, F2C, and F3C) were developed to observe the influence of water in the LCS, with the aim of achieving in situ gelling in the oral environment. These formulations were assessed by polarized light microscopy, small-angle X-ray scattering, rheological analysis, and in vitro bioadhesion analysis. Then, p1025 and a control (chlorhexidine) were incorporated into the aqueous phase of the formulation (F + p1025 and F + chlorhexidine), to determine their antibiofilm effect and toxicity on epithelial cells. Polarized light microscopy and small-angle X-ray scattering showed that F1C and F2C were LCS, whereas F3C was a microemulsion. F1C and F2C showed pseudoplastic behavior and F3C Newtonian behavior. F1C showed the highest elastic and bioadhesive characteristics compared to other formulations. Antibiofilm effects were observed for F + p1025 when applied in the surface-bound salivary phase. The p1025-loaded nanostructured LCS presented limited cytotoxicity and effectively reduced S. mutans biofilm formation, and could be a promising p1025-delivery strategy to prevent the formation of S. mutans dental biofilm.

Made available in DSpace on 2020-12-12T02:17:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-12-01 This study was performed to develop a liquid crystalline system (LCS) incorporated with terpinen-4-ol and nystatin to evaluate its antifungal, antibiofilm, and synergistic/modulatory activity against Candida albicans. The LCS was composed of a dispersion containing 40% propoxylated and ethoxylated cetyl alcohol, 40% oleic acid, and 0.5% chitosan dispersion. According to analysis by polarized light microscopy, rheology, and mucoadhesion studies, the incorporation of 100% artificial saliva increased the pseudoplasticity, consistency index, viscosity, and mucoadhesion of the formulation. The minimum inhibitory concentration, minimum fungicidal concentration, and rate of biofilm development were used to evaluate antifungal activity; the LCS containing terpinen-4-ol and nystatin effectively inhibited C. albicans growth at a lower concentration, displaying a synergistic action. Therefore, LCS incorporated with terpinen-4-ol and nystatin is a promising alternative for preventing and treating infections and shows potential for the development of therapeutic strategies against candidiasis. Department of Physiology and Pathology School of Dentistry of Araraquara Universidade Estadual Paulista UNESP Department of Drugs and Medicines School of Pharmaceutical of Araraquara UNESP Department of Physiological Sciences School of Dentistry of Piracicaba UNICAMP Department of Physiology and Pathology School of Dentistry of Araraquara Universidade Estadual Paulista UNESP Department of Drugs and Medicines School of Pharmaceutical of Araraquara UNESP

Made available in DSpace on 2019-10-06T17:13:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-08-01 The vaginal mucosa is a very promising route for drug administration due to its high permeability and the possibility to bypass first pass metabolism; however, current vaginal dosage forms present low retention times due to their dilution in vaginal fluids, which hampers the efficacy of many pharmacological treatments. In order to overcome these problems, this study proposes to develop a mucoadhesive in situ gelling liquid crystalline precursor system composed of 30% of oleic acid and cholesterol (7:1), 40% of ethoxylated and propoxylated cetyl alcohol, and 30% of a dispersion of 16% Poloxamer 407. The effect of the dilution with simulated vaginal fluid (SVF) on this system was evaluated by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), rheological studies, texture profile analysis (TPA), mucoadhesion study, in vitro drug release test using hypericin (HYP) as drug model, and cytotoxicity assay. PLM and SAXS confirmed the formation of an isotropic system. After the addition of three different concentrations of SVF (30, 50, and 100%), the resultant formulations presented anisotropy and characteristics of viscous lamellar phases. Rheology shows that formulations with SVF behaved as a non-Newtonian fluid with suitable shear thinning for vaginal application. TPA and mucoadhesion assays indicated the formation of long-range ordered systems as the amount of SVF increases which may assist in the fixation of the formulation on the vaginal mucosa. The formulations were able to control about 75% of the released HYP demonstrating a sustained release profile. Finally, all formulations acted as safe vaginal drug delivery systems. School of Pharmaceutical Sciences São Paulo State University (UNESP) Paraíba State University Center for Natural Sciences and Humanities Federal University of ABC (UFABC) School of Pharmaceutical Sciences São Paulo State University (UNESP)

Drug delivery systems (DDS) can be designed to enrich the pharmacological and therapeutic properties of several drugs. Many of the initial obstacles that impeded the clinical applications of conventional DDS have been overcome with nanotechnology-based DDS, especially those formed by chitosan (CS). CS is a linear polysaccharide obtained by the deacetylation of chitin, which has potential properties such as biocompatibility, hydrophilicity, biodegradability, non-toxicity, high bioavailability, simplicity of modification, aqueous solubility, and excellent chemical resistance. Furthermore, CS can prepare several DDS as films, gels, nanoparticles, and microparticles to improve delivery of drugs, such as photosensitizers (PS). Thus, CS-based DDS are broadly investigated for photodynamic therapy (PDT) of cancer and fungal and bacterial diseases. In PDT, a PS is activated by light of a specific wavelength, which provokes selective damage to the target tissue and its surrounding vasculature, but most PS have low water solubility and cutaneous photosensitivity impairing the clinical use of PDT. Based on this, the application of nanotechnology using chitosan-based DDS in PDT may offer great possibilities in the treatment of diseases. Therefore, this review presents numerous applications of chitosan-based DDS in order to improve the PDT for cancer and fungal and bacterial diseases.

Vulvovaginal candidiasis (VVC) is the most common infection caused by Candida albicans and greatly reduces the quality of life of women affected by it. Due to the ineffectiveness of conventional treatments, there is growing interest in research involving compounds of natural origin. One such compound is curcumin (CUR), which has been proven to be effective against this microorganism. However, some of CUR's physicochemical properties, especially its low aqueous solubility, make the therapeutic application of this compound difficult. Thus, the incorporation of CUR in mucoadhesive liquid crystalline systems (MLCSs) for vaginal administration may be an efficient strategy for the treatment of VVC. MLCSs are capable of potentiating the compound's action, releasing it in a controlled manner, and can enable longer exposure at the site of infection. In this study, MLCSs consisting of oleic acid and ergosterol 5:1 (w/w) as the oily phase, PPG-5-CETETH-20 as the surfactant, and a polymer dispersion of 1% chitosan as the aqueous phase, were developed for the application of CUR (MLCS-CUR) in VVC treatment. The formulations were characterized by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), oscillatory rheometry, continuous shear rheometry, texture profile analysis, and in vitro mucoadhesion. In addition, the antimicrobial activity was evaluated in vitro, and the effects on local fungal burden and cytokine profiles were investigated in a murine model of VVC. PLM and SAXS showed that the developed formulations presented a characteristic of a microemulsion. However, after the addition of artificial vaginal mucus (AVM), PLM showed that the formulations had structures similar to the "Maltese cross" characteristic of lamellar MLCS. Mucoadhesive test results showed an increase in the mucoadhesive strength of these formulations. Rheology analyses suggested long-lasting action of the formulation at the infected site. The in vitro antimicrobial activity assays suggested that CUR possesses antifungal activity against Candida albicans, determined after its incorporation into the MLCS. Further, MLCS-CUR was also more effective in vivo in the control of vaginal infection than treatment with fluconazole. Immunological assays showed that the ratio of pro-inflammatory (IL-1β) to anti-inflammatory (TGF-β) cytokines has decreased and that there is a reduction in the number of polymorphonuclear neutrophils recruited to the vaginal lumen, showing that treatment with MLCS-CUR was effective in modulating the inflammatory reaction associated with the infection. The results suggest that MLCSs could potentially be used in the treatment of VVC with CUR. Fil: Rodero, Camila Fernanda. Universidade Estadual Paulista Julio de Mesquita Filho; Brasil Fil: Fioramonti Calixto, Giovana Maria. Universidade Estadual Paulista Julio de Mesquita Filho; Brasil Fil: dos Santos, Karen Cristina. Universidade Estadual Paulista Julio de Mesquita Filho; Brasil Fil: Sato, Mariana Rillo. Universidade Estadual Paulista Julio de Mesquita Filho; Brasil Fil: Aparecido dos Santos Ramos, Matheus. Universidade Estadual Paulista Julio de Mesquita Filho; Brasil Fil: Miró, María Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Rodriguez, Emilse. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Vigezzi, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Bauab, Tais Maria. Universidade Estadual Paulista Julio de Mesquita Filho; Brasil Fil: Sotomayor, Claudia Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Chorilli, Marlus. Universidade Estadual Paulista Julio de Mesquita Filho; Brasil

Retinyl palmitate (RP) is widely used as a special interest ingredient in dermatological formulations to improve the elasticity of the skin and to reduce wrinkles by stimulating collagen synthesis. Nanotechnology-based drug delivery systems, such as liquid crystalline systems (LCSs), can modulate drug permeation into skin and improve the drug action. The effects of such systems on the skin, however, are not completely known. Possible undesirable effects of these formulations on the skin can be detected and interpreted by histopathology and histomorphometry. The objective of this study was to perform a rheological characterization to evaluate the safety of RP used in a lamellar LCS in vitro and in vivo. LCSs containing polyether functional siloxane as a surfactant, silicon glycol copolymer as an oil phase and water at ratios of 60:10:30 and 40:30:30, with (F₁v and F₂v, respectively) and without (F₁ and F₂ respectively) RP, were investigated. The rheological characterization was performed using steady shear rate sweep tests and dynamic frequency sweep tests carried out for up to 30 days for various storage temperature conditions (25 ± 2 °C, 37 ± 2 °C and 5 ± 2 °C). Cytotoxic effects were evaluated using J-774 mouse macrophages as a cellular model system. The in vivo tests were conducted on rabbits that had areas of skin treated as follows for 15 days: C (Control); F₁; F₁v; F₂; and F₂v. Histomorphometric and histopathological techniques were used to estimate the thicknesses of the epidermis and stratum corneum and the numbers of fibroblasts and leukocytes in the papillary dermis. Mean values were compared by ANOVA, followed by the Tukey test (p < 0.05). The steady shear rate sweep and dynamic frequency sweep tests confirmed the high viscosity of the LCS and the typical pseudo-plastic characteristic of the lamellar system. The RP-unloaded LCS and the RP-loaded LCS did not produce cytotoxicity, nor did they provoke significant thickening of the epidermis and stratum corneum. The number of leukocytes in the treated areas did not change; however, the number of fibroblasts in the area treated with F₁v was higher than in the areas treated with the control and F₂. The histological analyses demonstrated that none of the formulations irritated the skin and that formulation F₁v significantly increased the number of fibroblasts in the dermis, which could result in an increase in the production of collagen.

Made available in DSpace on 2015-10-21T21:00:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-01-01. Added 1 bitstream(s) on 2015-10-22T09:52:40Z : No. of bitstreams: 1 WOS000348787400001.pdf: 2503396 bytes, checksum: 997d94f04266d826752f42fe78fda2d3 (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Programa de Apoio ao Desenvolvimento Científico (PADC) Comision Sectorial de Investigacion Cientifica (CSIC) Cutaneous leishmaniasis (CL) is a resistant form of leishmaniasis that is caused by a parasite belonging to the genus Leishmania. FLU-loaded microemulsions (MEs) were developed by phase diagram for topical administration of fluconazole (FLU) as prominent alternative to combat CL. Three MEs called F1, F2, and F3 (F1-60% 50 M phosphate buffer at pH 7.4 (PB) as aqueous phase, 10% cholesterol (CHO) as oil phase, and 30% soy phosphatidylcholine/oil polyoxyl-60 hydrogenated castor oil/sodium oleate (3/8/6) (S) as surfactant; F2-50% PB, 10% CHO, and 40% S; F3-40% PB, 10% CHO, and 50 % S) were characterized by droplet size analysis, zeta potential analysis, X-ray diffraction, continuous flow, texture profile analysis, and in vitro bioadhesion. MEs presented pseudoplastic flow and thixotropy was dependent on surfactant concentration. Droplet size was not affected by FLU. FLU-loaded MEs improved the FLU safety profile that was evaluated using red cell haemolysis and in vitro cytotoxicity assays with J-774 mouse macrophages. FLU-unloaded MEs did not exhibit leishmanicidal activity that was performed using MTT colourimetric assays; however, FLU-loaded MEs exhibited activity. Therefore, these MEs have potential to modulate FLU action, being a promising platform for drug delivery systems to treat CL. Universidad de la República, Departamento de Química Orgánica, Facultad de Química-Facultad de Ciencias Universidade Estadual Paulista, Departamento de Fármacos e Medicamentos, Faculdade de Ciências Farmacêuticas de Araraquara Universidade Estadual Paulista, Departamento de Análises Clínicas, Faculdade de Ciências Farmacêuticas de Araraquara CSIC: 610

Bruno Fonseca-Santos,* Cínthia Yuka Satake,* Giovana Maria Fioramonti Calixto,* Aline Martins dos Santos, Marlus Chorilli School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, São Paulo, Brazil *These authors contributed equally tothis work Abstract: Resveratrol (Res) is a common phytoalexin present in a few edible materials, such as grape skin, peanuts, and red wine. Evidence has shown the beneficial effects of Res on human health, which may be attributed to its anti-inflammatory activity. However, the poor aqueous solubility of Res limits its therapeutic effectiveness. Therefore, the use of nanostructured delivery systems for Res, such as liquid-crystalline systems, could be beneficial. In this study, we aimed to develop, characterize, and determine the in vivo effectiveness of Res-loaded liquid-crystalline systems. Systems containing copaiba balsam oil, polyethylene glycol-40 hydrogenated castor oil, and water were designed. Results of polarized light microscopy, small-angle X-ray scattering, texture-profile analysis, and flow-rheology analysis showed that the Res-loaded liquid-crystalline system had a lamellar structure, textural and mechanical (hardness, compressibility, and adhesiveness) properties, and behaved as a non-Newtonian fluid, showing pseudoplastic behavior upon skin application. Furthermore, all liquid-crystalline systems presented bioadhesive properties that may have assisted in maintaining the anti-inflammatory activity of Res, since the topical application of the Res-loaded lamellar mesophase liquid crystals resulted in edema inhibition in a carrageenan-induced paw-inflammation mouse model. Therefore, Res-loaded lamellar mesophases represent a promising new therapeutic approach for inhibition of skin inflammation. Keywords: lamellar mesophase, liquid crystals, anti-inflammatory properties, topical delivery

Made available in DSpace on 2018-12-11T17:15:16Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-02-01 The buccal mucosa is accessible, shows rapid repair, has an excellent blood supply, and shows the absence of the first-pass effect, which makes it a very attractive drug delivery route. However, this route has limitations, mainly due to the continuous secretion of saliva (0.5 to 2 L/day), which may lead to dilution, possible ingestion, and unintentional removal of the active drug. Nanotechnology-based drug delivery systems, such as liquid crystalline systems (LCSs), can increase drug permeation through the mucosa and thereby improve drug delivery. This study aimed at developing and characterizing the mechanical, rheological, and mucoadhesive properties of four liquid crystalline precursor systems (LCPSs) composed of four different aqueous phases (i) water (FW), (ii) chitosan (FC), (iii) polyethyleneimine (FP), or (iv) both polymers (FPC); oleic acid was used as the oil phase, and ethoxylated and propoxylated cetyl alcohol was used as the surfactant. Polarized light microscopy and small-angle X-ray scattering indicated that all LCPSs formed liquid crystalline states after incorporation of saliva. Rheological, texture, and mucoadhesive assays showed that FPC had the most suitable characteristics for buccal application. In vitro release study showed that FPC could act as a controlled drug delivery system. Finally, based on in vitro cytotoxicity data, FPC is a safe buccal drug delivery system for the treatment of several buccal diseases. Faculdade de Ciências Farmacêuticas Departamento de Fármacos e Medicamentos UNESP—Universidade Estadual Paulista Campus Araraquara Araraquara Dental School UNESP- Univ Estadual Paulista Faculdade de Ciências Farmacêuticas Departamento de Fármacos e Medicamentos UNESP—Universidade Estadual Paulista Campus Araraquara Araraquara Dental School UNESP- Univ Estadual Paulista

Bioadhesiviness of polyacrylic acid polymers make them promising hydrogels to design topical drug delivery systems, allowing a close contact with biological substrate as well as an enhanced local concentration gradient, both factors that may improve the biological performance of the drugs.Texture and bioadhesive properties of hydrogels were assessed by using texture analyzer and they were correlated with their rheological behavior and performance as drug delivery systems.Aqueous dispersions of both polymers were prepared at 0.5%, 1.0% and 1.5% w/v. Hardness, compressibility, adhesiveness, cohesiveness, bioadhesion, continuous flow, oscillatory dynamic test and in vitro drug release were evaluated.Rheological and texture parameters were dependent on polymer concentration and C974P polymer built the strongest structures. Both 1.5% hydrogels presented high bioadhesion values. About 50% of the metronidazole (MTZ) was sustained released from hydrogels within 2 h with an initial burst release at early stage. After, the release rates were decreased and 10% of the MTZ was released in the next 10 h. The drug release process was driven by Fickian diffusion and complex mechanism for PP and C974P hydrogels, respectively.The set of results demonstrated that these hydrogels are promising to be used as topical controlled drug delivery system.

Liposomes containing hydrogenated soy phosphatidylcholine (PCH), with or without cholesterol (CHOL) and caffeine (CAF), were prepared by sonication and characterized for encapsulation efficiency and mean diameter. Dynamic light scattering assay showed that the incorporation of CHOL decreased significantly the size of the liposomes and led to a more heterogeneous distribution of size raising the CAF encapsulation efficiency. The in vitro drug release studies showed that the encapsulation of the CAF in liposomes produced a reduction in the release rate and the inclusion of CHOL in the liposome formulation delayed still further the release of the CAF.

Made available in DSpace on 2018-12-11T17:04:45Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-05-20 Antimicrobial photodynamic therapy (aPDT) is increasingly being explored for treatment of periodontitis. Here, we investigated the effect of aPDT on human dental plaque bacteria in suspensions and biofilms in vitro using methylene blue (MB)-loaded poly(lactic-co-glycolic) (PLGA) nanoparticles (MB-NP) and red light at 660 nm. The effect of MB-NP-based aPDT was also evaluated in a clinical pilot study with 10 adult human subjects with chronic periodontitis. Dental plaque samples from human subjects were exposed to aPDT—in planktonic and biofilm phases—with MB or MB-NP (25 μ/mL) at 20 J/cm2 in vitro. Patients were treated either with ultrasonic scaling and scaling and root planing (US + SRP) or ultrasonic scaling + SRP + aPDT with MB-NP (25 μ/mL and 20 J/cm2) in a split-mouth design. In biofilms, MB-NP eliminated approximately 25% more bacteria than free MB. The clinical study demonstrated the safety of aPDT. Both groups showed similar improvements of clinical parameters one month following treatments. However, at three months ultrasonic SRP + aPDT showed a greater effect (28.82%) on gingival bleeding index (GBI) compared to ultrasonic SRP. The utilization of PLGA nanoparticles encapsulated with MB may be a promising adjunct in antimicrobial periodontal treatment. Faculdade de Ciencias Farmaceuticas UNESP—Univ Estadual Paulista Departamento de Análises Clínicas, Campus Araraquara Faculdade de Ciencias Farmaceuticas UNESP—Univ Estadual Paulista Departamento de Farmacos e Medicamentos, Campus Araraquara Instituto de Fisica de Sao Carlos Universidade de Sao Paulo, Caixa Postal 369 Applied Molecular Photomedicine Laboratory The Forsyth Institute, 245 First Street Department of PharmaceuticalSciences School of Pharmacy Bouvé College of Health Sciences Northeastern University, 140 The Fenway, Room 156, 360 Huntington Avenue Faculdade de Ciencias Farmaceuticas UNESP—Univ Estadual Paulista Departamento de Análises Clínicas, Campus Araraquara Faculdade de Ciencias Farmaceuticas UNESP—Univ Estadual Paulista Departamento de Farmacos e Medicamentos, Campus Araraquara

Made available in DSpace on 2018-12-11T17:28:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-05-01 Tuberculosis (TB) is an infectious disease caused mainly by the bacillus Mycobacterium tuberculosis (Mtb), presenting 9.5 million new cases and 1.5 million deaths in 2014. The aim of this study was to evaluate a nanostructured lipid system (NLS) composed of 10% phase oil (cholesterol), 10% surfactant (soy phosphatidylcholine, sodium oleate), and Eumulgin® HRE 40 ([castor oil polyoxyl-40-hydrogenated] in a proportion of 3:6:8), and an 80% aqueous phase (phosphate buffer pH = 7.4) as a tactic to enhance the in vitro anti-Mtb activity of the copper(II) complexes [CuCl2(INH)2] H2O (1), [Cu(NCS)2(INH)2]5H2O (2) and [Cu(NCO)2(INH)2]4H2O (3). The Cu(II) complex-loaded NLS displayed sizes ranging from 169.5 ± 0.7095 to 211.1 ± 0.8963 nm, polydispersity index (PDI) varying from 0.135 ± 0.0130 to 0.236 ± 0.00100, and zeta potential ranging from -0.00690 ± 0.0896 to 8.43 ± 1.63 mV. Rheological analysis showed that the formulations behave as non-Newtonian fluids of the pseudoplastic and viscoelastic type. Antimycobacterial activities of the free complexes and NLS-loaded complexes against Mtb H37Rv ATCC 27294 were evaluated by the REMA methodology, and the selectivity index (SI) was calculated using the cytotoxicity index (IC50) against Vero (ATCC® CCL-81), J774A.1 (ATCC® TIB-67), and MRC-5 (ATCC® CCL-171) cell lines. The data suggest that the incorporation of the complexes into NLS improved the inhibitory action against Mtb by 52-, 27-, and 4.7-fold and the SI values by 173-, 43-, and 7-fold for the compounds 1, 2 and 3, respectively. The incorporation of the complexes 1, 2 and 3 into the NLS also resulted in a significant decrease of toxicity towards an alternative model (Artemia salina L.). These findings suggest that the NLS may be considered as a platform for incorporation of metallic complexes aimed at the treatment of TB. Faculdade de Ciencias Farmaceuticas UNESP—Univ Estadual Paulista, Campus Araraquara Instituto de Química UNESP—Univ Estadual Paulista, Campus Araraquara Faculdade de Ciencias Farmaceuticas UNESP—Univ Estadual Paulista, Campus Araraquara Instituto de Química UNESP—Univ Estadual Paulista, Campus Araraquara

Hydrogels are widely used for cutaneous formulations; thereby comparing the bioadhesive properties of polymers with a view to prolong the residence time of topical drugs on the skin would be very useful to design novel topical drug delivery systems.The objective of this study was to correlate data from rheological studies and texture profile analysis, with bioadhesion on the skin.Polyacrylic acid polymers used were carbomer homopolymer type A (C971) and type B (C974), and polycarbophil (PP) dispersed in water at various concentrations (0.1, 0.5, 1.0, 1.5, 2.0, 3.0, 5.0%, w/v). Rheological, texture, and bioadhesive properties were determined to compare the hydrogels.Rheological analysis showed that all samples exhibited pseudoplastic behavior with thixotropy. Texture profile analysis showed that compressibility, hardness, and adhesiveness of the hydrogels were dependent on the polymer concentration, and the cohesion values were high. Bioadhesion of C974 and PP at 0.5 and 2% was of the same magnitude, while all samples of C971 had lower values. The bioadhesion of 5% C974 was the highest, while that 5% PP was lower, possibly because PP showed the greatest hardness and this rigidity may decrease the interaction of the polymer with the skin.A comprehensive comparative rheological and textural analyses of several polymers for topical systems were undertaken in terms of their bioadhesion. Therefore, it is possible to conclude that these polymers can be used for optimization of drug delivery systems on the skin.

Made available in DSpace on 2018-12-11T17:24:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-02-18 Methotrexate (MTX) is an immunosuppressive drug for systemic use in the treatment of skin diseases, however, MTX presents a number of side effects, such as hepatotoxicity. To overcome this limitation, this study developed skin MTX delivery surfactant systems, such as a microemulsion (ME) and a liquid crystalline system (LCS), consisting of a glycol copolymer-based silicone fluid (SFGC) as oil phase, polyether functional siloxane (PFS) as surfactant, and carbomer homopolymer type A (C971) dispersion at 0.5% (wt/wt) as aqueous phase. Polarized light microscopy and small-angle X-ray scattering evidenced the presence of hexagonal and lamellar LCSs, and also a ME. Texture profile and in vitro bioadhesion assays showed that these formulations are suitable for topical application, showing interesting hardness, adhesiveness and compressibility values. Rheology analysis confirmed the Newtonian behaviour of the ME, whereas lamellar and hexagonal LCSs behave as pseudoplastic and dilatant non-Newtonian fluids, respectively. In vitro release profiles indicated that MTX could be released in a controlled manner from all the systems, and the Weibull model showed the highest adjusted coefficient of determination. Finally, the formulations were not cytotoxic to the immortalized human keratinocyte line HaCaT. Therefore, these bioadhesive surfactant systems established with PFS and C971 have great potential as skin delivery systems. Faculdade de Ciências Farmacêuticas, UNESP-Universidade Estadual Paulista, Campus Araraquara, Departamento de Fármacos e Medicamentos, Araraquara, SP, 14800-850, Brazil Faculdade de Ciências Farmacêuticas, UNESP-Universidade Estadual Paulista, Campus Araraquara, Departamento de Fármacos e Medicamentos, Araraquara, SP, 14800-850, Brazil. larissa_alvarenga@ymail.com Faculdade de Ciências Farmacêuticas, UNESP-Universidade Estadual Paulista, Campus Araraquara, Departamento de Análises Clínicas, Araraquara, SP 14800-850, Brazil Faculdade de Ciências Farmacêuticas, UNESP-Universidade Estadual Paulista, Campus Araraquara, Departamento de Fármacos e Medicamentos, Araraquara, SP, 14800-850, Brazil. eliete.vz@gmail.com Faculdade de Ciências Farmacêuticas, UNESP-Universidade Estadual Paulista, Campus Araraquara, Departamento de Fármacos e Medicamentos, Araraquara, SP, 14800-850, Brazil. pgremiao@fcfar.unesp.br

Made available in DSpace on 2018-12-11T17:30:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-01-01 Decapeptide KSL-W shows antibacterial activities and can be used in the oral cavity, however, it is easily degraded in aqueous solution and eliminated. Therefore, we aimed to develop liquid crystalline systems (F1 and F2) for KSL-W buccal administration to treat multispecies oral biofilms. The systems were prepared with oleic acid, polyoxypropylene (5) polyoxyethylene (20) cetyl alcohol (PPG-5-CETETH-20), and a 1% poloxamer 407 dispersion as the oil phase (OP), surfactant (S), and aqueous phase (AP), respectively. We characterized them using polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), rheology, and in vitro bioadhesion, and performed in vitro biological analysis. PLM showed isotropy (F1) or anisotropy with lamellar mesophases (F2), confirmed by peak ratio quantification using SAXS. Rheological tests demonstrated that F1 exhibited Newtonian behavior but not F2, which showed a structured AP concentration-dependent system. Bioadhesion studies revealed an AP concentration-dependent increase in the system's bioadhesiveness (F2 = 15.50 ±1.00 mN s) to bovine teeth blocks. Antimicrobial testing revealed 100% inhibition of multispecies oral biofilm growth after KSL-W administration, which was incorporated in the F2 aqueous phase at a concentration of 1 mg/mL. Our results suggest that this system could serve as a potential vehicle for buccal administration of antibiofilm peptides. School of Pharmaceutical Sciences Sao Paulo State University UNESP, Rodovia Araraquara-Jaú Km 01 Chemistry Institute UNESP Sao Paulo State University School of Pharmaceutical Sciences Sao Paulo State University UNESP, Rodovia Araraquara-Jaú Km 01 Chemistry Institute UNESP Sao Paulo State University

Made available in DSpace on 2015-10-21T20:58:39Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-01-01. Added 1 bitstream(s) on 2015-10-22T09:52:41Z : No. of bitstreams: 1 WOS000350581800001.pdf: 1957346 bytes, checksum: 39fdff32d081523013b0d27dfe19e5d1 (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Multiple emulsions (MEs) are intensively being studied for drug delivery due to their ability to load and increase the bioavailability of active lipophilic antioxidant, such as kojic dipalmitate (KDP). The aim of this study was to structurally characterize developed MEs by determining the average droplet size (Dnm) and zeta potential (ZP), performing macroscopic and microscopic analysis and analyzing their rheological behavior and in vitro bioadhesion. Furthermore, the in vitro safety profile and antioxidant activity of KDP-loaded MEs were evaluated. The developed MEs showed a Dnm of approximately 1 micrometer and a ZP of -13mV, and no change was observed in Dnm or ZP of the system with the addition of KDP. KDP-unloaded MEs exhibited "shear thinning" flow behavior whereas KDP-loaded MEs exhibited Newtonian behavior, which are both characteristic of antithixotropic materials. MEs have bioadhesion properties that were not influenced by the incorporation of KDP. The results showed that the incorporation of KDP into MEs improved the safety profile of the drug. The in vitro antioxidant activity assay suggested that MEs presented a higher capacity for maintaining the antioxidant activity of KDP. ME-based systems may be a promising platform for the topical application of KDP in the treatment of skin disorders. Universidade Estadual Paulista, Departamento de Fármacos e Medicamentos, Faculdade de Ciências Farmacêuticas de Araraquara

New biocompatible nanomaterials are leading to a range of emerging health treatments. Thus, peptide drugs present in oral diseases, such as caries, periodontal diseases and oral cancer, are highlighting into clinical practice because the peptides can have an influence the growth of tumor cells or microorganisms and its can exhibit direct cytotoxic activity towards cancer cells or microbial cells. Therefore, it is interesting to speculate what are the natural or synthetic peptides that can be used to develop novel strategies to fight cancer diseases or microbial cells, and so, to represent a novel family of anticancer or antimicrobial agents. The use of buccal drug delivery systems, especially nanoparticles, to carrier peptides shows to be very interesting, because these systems can protect the peptide against enzymatic degradation, in addition to target inaccessible sites. However, this peptide delivery system seems to be unexplored by researchers. On the hand, the application of drug delivery systems for oral diseases could be a proposed treatment for these diseases, including the treatment or co-treatment with other therapies, such as photodynamic therapy, of antimicrobial, periodontal diseases and cancer, or even in the early diagnosis of cancer. The objective of this study is to present a systematic review of nanotechnology-based peptides delivery systems intended to oral diseases.

Made available in DSpace on 2018-12-11T17:31:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-01-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Camellia sinensis, which is obtained from green tea extract (GTE), has been widely used in therapy owing to the antioxidant, chemoprotective, and anti-inflammatory activities of its chemical components. However, GTE is an unstable compound, and may undergo reactions that lead to a reduction or loss of its effectiveness and even its degradation. Hence, an attractive approach to overcome this problem to protect the GTE is its incorporation into liquid crystalline systems (LCS) that are drug delivery nanostructured systems with different rheological properties, since LCS have both fluid liquid and crystalline solid properties. Therefore, the aim of this study was to develop and characterize GTE-loaded LCS composed of polyoxypropylene (5) polyoxyethylene (20) cetyl alcohol, avocado oil, and water (F25E, F29E, and F32E) with different rheological properties and to determine their anti-inflammatory efficacy. Polarized light microscopy revealed that the formulations F25, F29, and F32 showed hexagonal, cubic, and lamellar liquid crystalline mesophases, respectively. Rheological studies showed that F32 is a viscous Newtonian liquid, while F25 and F29 are dilatant and pseudoplastic non-Newtonian fluids, respectively. All GTE-loaded LCS behaved as pseudoplastic with thixotropy; furthermore, the presence of GTE increased the S values and decreased the n values, especially in F29, indicating that this LCS has the most organized structure. Mechanical and bioadhesive properties of GTE-unloaded and -loaded LCS corroborated the rheological data, showing that F29 had the highest mechanical and bioadhesive values. Finally, in vivo inflammation assay revealed that the less elastic and consistent LCS, F25E and F32E presented statistically the same anti-inflammatory activity compared to the positive control, decreasing significantly the paw edema after 4 h; whereas, the most structured and elastic LCS, F29E, strongly limited the potential effects of GTE. Thereby, the development of drug delivery systems with suitable rheological properties may enhance GTE bioavailability, enabling its administration via the skin for the treatment of inflammation. School of Pharmaceutical Sciences São Paulo State University-UNESP, Rodovia Araraquara-Jaú, km. 1, Campus School of Pharmaceutical Sciences São Paulo State University-UNESP, Rodovia Araraquara-Jaú, km. 1, Campus

Made available in DSpace on 2018-12-11T17:04:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-08-22 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Herbal-loaded drug delivery nanotechnological systems have been extensively studied recently. The antimicrobial activity of medicinal plants has shown better pharmacological action when such plants are loaded into a drug delivery system than when they are not loaded. Syngonanthus nitens Bong. (Rhul.) belongs to the Eriocaulaceae family and presents antiulcerogenic, antioxidant, antibacterial, and antifungal activity. The aim of this study was to evaluate the antifungal activity of Syngonanthus nitens (S. nitens) extract that was not loaded (E) or loaded (SE) into a liquid crystal precursor system (S) for the treatment of vulvovaginal candidiasis (VVC) with Candida albicans. The minimal inhibitory concentration (MIC) was determined by the microdilution technique. Additionally, we performed hyphae inhibition and biofilm tests. Finally, experimental candidiasis was evaluated in in vivo models with Wistar female rats. The results showed effective antifungal activity after incorporation into S for all strains tested, with MICs ranging from 31.2 to 62.5 μg/mL. Microscopic observation of SE revealed an absence of filamentous cells 24 h of exposure to a concentration of 31.2 μg/mL. E demonstrated no effective action against biofilms, though SE showed inhibition against biofilms of all strains. In the in vivo experiment, SE was effective in the treatment of infection after only two days of treatment and was more effective than E and amphotericin B. The S. nitens is active against Candida albicans (C. albicans) and the antifungal potential is being enhanced after incorporation into liquid crystal precursor systems (LCPS). These findings represent a promising application of SE in the treatment of VVC. Department of Biological Sciences School of Pharmaceutical Sciences UNESP-Univ Estadual Paulista Department of Drugs and Medicines School of Pharmaceutical Sciences UNESP-Univ Estadual Paulista Federal University of São João Del-Rey Department of Organic Chemistry Chemisty Institute UNESP-Univ Estadual Paulista Department of Infectious Diseases Faculty of Medicine of São José do Rio Preto-FAMERP Department of Biological Sciences School of Pharmaceutical Sciences UNESP-Univ Estadual Paulista Department of Drugs and Medicines School of Pharmaceutical Sciences UNESP-Univ Estadual Paulista Department of Organic Chemistry Chemisty Institute UNESP-Univ Estadual Paulista FAPESP: 2013/25432-0 FAPESP: 2016/13784-8

Matheus Aparecido dos Santos Ramos,1 Giovana Calixto,2 Luciani Gaspar de Toledo,3 Bruna Vidal Bonifácio,1 Lourdes Campaner dos Santos,4 Margarete Teresa Gottardo de Almeida,3 Marlus Chorilli,2 Taís Maria Bauab1 1Department of Biological Sciences, School of Pharmaceutical Sciences, 2Department of Drugs and Medicine, School of Pharmaceutical Sciences, São Paulo State University, Araraquara, 3Department of Infectious Diseases, Faculty of Medicine of São José do Rio Preto, São José do Rio Preto, 4Department of Organic Chemistry, Chemistry Institute, São Paulo State University, Araraquara, São Paulo, Brazil Abstract: Vaginal infections caused by Candida krusei are a problem of extreme complexity due to the intrinsic resistance to azole drugs. The species Syngonanthus nitens (Bong.) Ruhland is a plant of the Eriocaulaceae family that has demonstrated promising antifungal activity. In phyto-formulation research, liquid crystal precursor mucoadhesive systems (LCPM) stand out as drug delivery systems for vaginal administration because they increase the activity and overcome the problems associated with plant-based medicines. Therefore, the objective of this study was to evaluate the potential of the methanolic extract of scapes of S. nitens (S. nitens extract [SNE]) and an SNE-loaded LCPM against C. krusei as prophylaxis for vulvovaginal candidiasis. LCPM formulation developed consisted of oleic acid as the oil phase (50% w/w), polyoxypropylene (5) polyoxyethylene (20) cetyl alcohol (40% w/w) as the surfactant and a polymeric dispersion containing 2.5% Carbopol® 974P and 2.5% polycarbophil (10% w/w) as the aqueous phase. LCPM formulation developed was characterized using polarized light microscopy, rheological analysis, and in vitro mucoadhesive studies. Different strains of C. krusei, including one standard strain (American Type Culture Collection 6258) and three clinically isolated strains from the vaginal region (CKV1, 2, and 3), were used to determine the minimum inhibitory concentration, inhibition of biofilms, and time kill. The in vivo prophylaxis assay was performed using the standard strain (American Type Culture Collection 6258). The analyses of F by polarized light microscopy and rheology showed isotropy; however, the addition of 100% artificial vaginal mucus (F100) made it more viscous and anisotropic. Moreover, the mucoadhesive strength was modified, which makes F an excellent formulation for vaginal applications. SNE was active against all strains studied, with minimum inhibitory concentration values ranging from 125 to 62.5 µg/mL; after incorporating SNE into F (FE), these values decreased to 62.5 to 31.2 µg/mL, demonstrating that incorporation into the formulation potentiated the action of SNE. Additionally, the time kill assays showed that both forms of SNE were capable of controlling growth, thereby suggesting a possible fungistatic mechanism. Unloaded SNE was not active against C. krusei biofilms, but FE was active against a clinical strain (CKV2). In vivo analysis showed that FE was able to prevent the development of infection following 10 days of administration. We concluded that the formulation developed in this study was an important vehicle for the delivery of SNE based on the improved antifungal activity in all in vitro and in vivo analyses. Furthermore, the extract incorporated into the system may serve as an important prophylactic agent against vaginal infections caused by C. krusei. Keywords: precursor system of mucoadhesive liquid crystal, nanostructured system, ­prophylaxis, Candida krusei

Made available in DSpace on 2015-12-07T15:34:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2015. Added 1 bitstream(s) on 2015-12-07T15:54:19Z : No. of bitstreams: 1 PMC4525803.pdf: 1159237 bytes, checksum: 5d62bb3d5bc2b343d38c60e292cb8188 (MD5) Women often develop vaginal infections that are caused primarily by organisms of the genus Candida. The current treatments of vaginal candidiasis usually involve azole-based antifungals, though fungal resistance to these compounds has become prevalent. Therefore, much attention has been given to molecules with antifungal properties from natural sources, such as curcumin (CUR). However, CUR has poor solubility in aqueous solvents and poor oral bioavailability. This study attempted to overcome this problem by developing, characterizing, and evaluating the in vitro antifungal action of a CUR-loaded liquid crystal precursor mucoadhesive system (LCPM) for vaginal administration. A low-viscosity LCPM (F) consisting of 40% wt/wt polyoxpropylene-(5)-polyoxyethylene-(20)-cetyl alcohol, 50% wt/wt oleic acid, and 10% wt/wt chitosan dispersion at 0.5% with the addition of 16% poloxamer 407 was developed to take advantage of the lyotropic phase behavior of this formulation. Notably, F could transform into liquid crystal systems when diluted with artificial vaginal mucus at ratios of 1:3 and 1:1 (wt/wt), resulting in the formation of F30 and F100, respectively. Polarized light microscopy and rheological studies revealed that F behaved like an isotropic formulation, whereas F30 and F100 behaved like an anisotropic liquid crystalline system (LCS). Moreover, F30 and F100 presented higher mucoadhesion to porcine vaginal mucosa than F. The analysis of the in vitro activity against Candida albicans revealed that CUR-loaded F was more potent against standard and clinical strains compared with a CUR solution. Therefore, the vaginal administration of CUR-loaded LCPMs represents a promising platform for the treatment of vaginal candidiasis. School of Pharmaceutical Sciences, UNESP - Sao Paulo State University, Campus Araraquara, Department of Drugs and Medicines, Araraquara, Sao Paulo, Brazil. School of Pharmaceutical Sciences, UNESP - Sao Paulo State University, Campus Araraquara, Department of Drugs and Medicines, Araraquara, Sao Paulo, Brazil.

Made available in DSpace on 2022-04-29T07:24:27Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-01-01 An innovative microbiological assay was developed for the determination of colistin sulphate at various concentrations (192-469 IU/mL); using Bordetella bronchiseptica ATCC 4617 as microorganism test. This assay revealed subtle changes not demonstrated by chemical methods, such as chemical degradation and low of potency, but by evaluating the potency of colistin, which is very important for the analysis of antibiotics. The method was validated according to ICH guidelines, proving to be linear (r2 = 0.9985), precise (CV = 1.32%) and accurate (100.9 ± 1.33%). It was concluded that the microbiological assay is satisfactory for in vitro quantitation of the antibacterial activity of colistin sulphate. School of Pharmaceutical Sciences Departament of Drugs and Pharmaceuticals São Paulo State University, Rodovia Araraquara/Jaú School of Health Sciences Methodist University of Piracicaba, Rodovia do Açúcar School of Pharmaceutical Sciences Departament of Drugs and Pharmaceuticals São Paulo State University, Rodovia Araraquara/Jaú