Publications by authors named "Thiago Caon"

32 Publications

In vitro anti-inflammatory properties of honey flavonoids: A review.

Food Res Int 2021 Mar 29;141:110086. Epub 2020 Dec 29.

Department of Food Science and Technology, Federal University of Santa Catarina, Florianópolis, SC, Brazil. Electronic address:

Honey is a natural ready-to-eat product rich in flavonoids, which is known by the wound healing properties due to both antibacterial and antioxidant activity. Flavonoids mitigate inflammatory processes, and thus it could currently support studies of anti-inflammatory potential of honeys. In this review, in vitro anti-inflammatory properties of flavonoids found in honey were prioritized. Mechanistic information of specific isolated flavonoids as modulators of inflammatory processes are summarized aiming to stimulate studies regarding the action of honey in inflammatory events. Lastly, a structure-activity relationship (SAR) of flavonoids was also included. Flavonoids found in honey have demonstrated antioxidant properties and ability to inhibit pro-inflammatory enzymes such as COX, LOX, iNOS, and pro-inflammatory mediators, including nitric oxide, cytokines and chemokines. Transcriptional factors such as NF-κB are also modulated by flavonoids, controlling the expression of several inflammatory mediators. SAR studies demonstrate the effect of flavonoids in the prevention of inflammatory cascades. Despite the promising reports of in vitro anti-inflammatory activity, well-designed clinical trials need yet to be performed to confirm the benefits of honeys from different botanical sources in diseases that include episodes of inflammation.
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http://dx.doi.org/10.1016/j.foodres.2020.110086DOI Listing
March 2021

Thermosensitive hydrogels for vaginal delivery of secnidazole as an approach to overcome the systemic side-effects of oral preparations.

Eur J Pharm Sci 2021 Apr 19;159:105722. Epub 2021 Jan 19.

Department of Pharmaceutical Sciences, Federal University of Santa Catarina, Campus Reitor João David Ferreira Lima, s/n - Trindade, Florianópolis - SC, 88040-900, Brazil. Electronic address:

Secnidazole (SEC) has been suggested as an alternative agent against Trichomonas vaginalis to overcome the adverse effects, antimicrobial resistance problems and poor adherence to the currently available therapy. Once no topical formulation may be found in the market until now, SEC was incorporated in thermosensitive bioadhesive systems to extend the contact time in the mucosa and to avoid a systemic drug disposition. Formulations containing 20% poloxamer 407, 1% poloxamer 188 and 1 or 2.5% chitosan showed suitable sol-gel transition temperature (> 30 °C), presenting a fast gelation time (100-115 s). Rheological, dynamic light scattering and infrared spectroscopy analysis suggested molecular interactions among polymers. Chitosan increased the mucoadhesion strength of the formulations. In addition, hydrogels showed a tendency to decrease the drug transport rate through mucosa when compared to the control. Mucin was also added onto mucosa for a more realistic simulation of permeability/retention. In the presence of this agent, hydrogels containing chitosan reduced the permeability/retention of the drug in approximately 2.0-fold when compared to the control. Therefore, the hydrogels presented suitable characteristics to remain in the vaginal environment, which would result in effective local treatment of trichomoniasis.
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http://dx.doi.org/10.1016/j.ejps.2021.105722DOI Listing
April 2021

Development and characterization of thermopressed polyvinyl alcohol films for buccal delivery of benznidazole.

Mater Sci Eng C Mater Biol Appl 2021 Feb 30;119:111546. Epub 2020 Sep 30.

Department of Pharmaceutical Sciences, Federal University of Santa Catarina, Campus Reitor João David Ferreira Lima, s/n - Trindade, Florianópolis, SC 88040-900, Brazil. Electronic address:

Given that oral preparations of benznidazole (BZN) have demonstrated limited efficacy in the treatment of Chagas' disease due to pharmacokinetic or toxicological problems, the development of buccal polymeric films was purposed in this study. These systems ensure high patient acceptability and direct access to the systemic circulation, improving drug bioavailability and toxicological profile. Polymer films were prepared through a thermopressing method by mixing BZN and polyvinyl alcohol (PVAL). In some preparations, propylene glycol (PG) and thymol (TM) were also included as plasticizer and chemical absorption enhancer, respectively. Morphology, X-ray diffraction, spectroscopic, thermal, mechanical, and water uptake properties, as well as ex vivo permeability studies, were performed to characterize the film formulations. BZN remained stable and in an amorphous form over 90 days. The addition of PG and TM improved the mechanical properties of the films, making them soft, flexible and tear-resistant. Also, these additives increased the water sorption rate of the films at 50 and 75% relative humidity and the TM increased the film erosion properties and drug permeability (close to 6×) compared to control. It was hypothesized that the permeability improvement of thymol-based films that follow a drug release profile through erosion is also associated with the inhibition of the crystallization of BNZ when the film is in contact with the buccal mucosa. Once the thymol has previously demonstrated a significant in vivo and in vitro trypanocidal action and even improved film characteristics, these systems may be considered promising for Chagas' disease treatment.
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http://dx.doi.org/10.1016/j.msec.2020.111546DOI Listing
February 2021

Emerging Technologies to Target Drug Delivery to the Skin - the Role of Crystals and Carrier-Based Systems in the Case Study of Dapsone.

Pharm Res 2020 Nov 9;37(12):240. Epub 2020 Nov 9.

Postgraduate Program in Pharmacy (PGFar), Federal University of Santa Catarina, Trindade, SC, 88040-900, Florianopolis, Brazil.

Dapsone (DAP) is a long-established molecule that remains a promising therapeutic agent for various diseases mainly because it combines antimicrobial and anti-inflammatory activities. Its oral application, however, is limited by the dose-dependent hematological side effects that may rise from systemic exposure. As an alternative to overcome this limitation, the administration of DAP to the skin has witnessed prominent interest in the past 20 years, particularly when applied to the treatment of dermatological disorders. In this review, all technological strategies proposed to the topical delivery of DAP are presented. Most of the reported studies have been devoted to the clinical use and safety of a gel formulation containing both solubilized and microcrystalline drug, however, the technological characteristics of such preparation are still missing. In parallel, the incorporation of DAP into vesicular and particulate carriers (e.g. nano- and microemulsions, niosomes, invasomes, bilosomes, cubosomes, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanocapsules and polymer-lipid-polymer hybrid nanoparticles) appears to be an alternative to provide greater drug release control, enhanced drug solubilization and follicular targeting. Indeed, the main application of DAP topical formulations reported in the literature was the treatment of acne vulgaris, a disease located in the hair follicle. Other diseases affecting different regions of the skin (e.g. cutaneous lupus erythematosus and cutaneous leishmaniasis), however, may also benefit from a topical therapeutic regimen containing DAP. Therefore, the investigation of appendageal route in comparison to passive transmembrane diffusion as a function of targeted disease, as well as pharmacokinetic studies, are perspectives highlighted herein. Such studies may drive future efforts towards the rational development of safe and effective technologies to deliver DAP to the skin. Graphical abstract.
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http://dx.doi.org/10.1007/s11095-020-02951-4DOI Listing
November 2020

Transbuccal Delivery of Isoniazid: Ex Vivo Permeability and Drug-Surfactant Interaction Studies.

AAPS PharmSciTech 2020 Oct 20;21(8):289. Epub 2020 Oct 20.

Programa de Pós-Graduação em Farmácia, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, 88040-900, Brazil.

The oral administration of isoniazid (INH) may lead to discontinuation of tuberculosis treatment due to drug-related hepatotoxicity events, and thus, the transbuccal delivery of this drug was investigated, for the first time, as an alternative administration route. Ex vivo permeability assays were performed in Franz-type diffusion chambers, applying INH alone and in combination with sodium dodecyl sulfate (SDS) and sodium taurocholate (ST). After confirming the formation of micelle structures by dynamic light scattering analysis, UV-visible spectroscopy and zeta potential analyses were used to investigate drug-micelle interactions. In zeta potential analyses, no electrostatical interactions were identified for both surfactants in saliva buffer pH 6.8. Spectrophotometric analyses, in turn, indicated chemical interactions between INH and SDS in both pH values (2.0 and 6.8) whereas no interaction between the drug and ST was observed. Despite the interaction between SDS and drug, this surfactant increased the buccal transport rate of INH by approximately 11 times when compared with the control. In contrast, ST did not increase the drug permeability. The INH retention in SDS-treated mucosa was significantly higher when compared with the control and an effect on intercellular lipids was suggested. In vivo studies are needed to confirm the high INH absorption found here. Grapical abstract.
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http://dx.doi.org/10.1208/s12249-020-01827-5DOI Listing
October 2020

Transbuccal delivery of metal complexes of isoniazid as an alternative to overcome antimicrobial resistance problems.

Int J Pharm 2020 Nov 11;590:119924. Epub 2020 Oct 11.

Programa de Pós-Graduação em Farmácia, Centro de Ciências da Saúde, Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC, Brazil. Electronic address:

In isolated isoniazid (INH)-resistant strains, deletion or mutations in thekatGgene have been identified, which result in loss of catalase-peroxidase activity. This enzyme plays a key role in the activation of this prodrug. As an alternative, the coordination of the INH to metal complexes has been purposed to activate it regardless of enzyme functionality. Although pentacyanido(isoniazid)ferrate(II) complexes have shown to be effective against resistant strains of Mycobacterium tuberculosis, low oral bioavailability was found. In this context, buccal mucosa was selected as an alternative route to the metal complex delivery. Moreover, oral manifestations of tuberculosis(TB) have been observed in some patients, particularly when resistant strains are present, and no therapeutic options are currently available on the market. Pentacyanidoferrate (PCF-INH) and Prussian-blue (PB-INH) complexes were initially prepared and characterized, followed by buccal permeability studies in Franz-type diffusion cells. The electrochemical potential of the complexes demonstrated their ability to self-activate. Job's method suggested the presence of structural defects in PB-INH complexes, which was correlated with permeability results. In fact, PB-INH showed a higher dissociation rate in salt-rich aqueous medium and thus a high transport rate of INH through the buccal mucosa. Its passage through the tissue would not be possible due to the high molecular size. PCF-INH, in turn, presented a lower dissociation rate in the salt-rich aqueous medium, justifying its slower transport rate through the tissue. Taken together, these results suggest that INH-based metal complexes may be efficiently administered through the buccal route, impacting on both oral bioavailability and microbial resistance.
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http://dx.doi.org/10.1016/j.ijpharm.2020.119924DOI Listing
November 2020

Development of curcumin-loaded chitosan/pluronic membranes for wound healing applications.

Int J Biol Macromol 2020 Nov 29;163:167-179. Epub 2020 Jun 29.

Polimat, Grupo de Estudos em Materiais Poliméricos, Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil. Electronic address:

The emergence of new materials with improved antibacterial, anti-inflammatory and healing properties compared to conventional wound dressings has both social and economic appeal. In this study, novel chitosan-based (CTS) membranes containing curcumin (CUR) incorporated in Pluronic (PLU) copolymers were developed and characterized to obtain suitable properties for applications as a wound healing dressing. The mechanical, thermal, swelling, wettability, release and permeation properties were evaluated by DSC, TGA, water contact angle measurements, FTIR, fluorescence and microscopic techniques. Membranes containing PLU and CUR presented wettability close to the ideal range for interaction with cellular components (contact angle ~40-70°), improved mechanical properties, higher thermal stability, high swelling degree (>800%) and CUR release (~60%) compared to samples without PLU addition. A higher retention of CUR in the epidermis than in the dermis layer was observed, which also was confirmed by confocal microscopy. Furthermore, the CTS-PLU membranes loaded with CUR showed to be active against Staphylococcus aureus and Pseudomonas aeruginosa (MIC = 25 and 100 mg mL, respectively), the microbial species most present in chronic wounds. Overall, the CTS-PLU-CUR membranes presented suitable properties to act as a new wound healing dressing formulation and in vivo studies should be performed to confirm these benefits.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.06.253DOI Listing
November 2020

Investigation of phenolic compounds, antioxidant and anti-inflammatory activities in stingless bee honey (Meliponinae).

Food Res Int 2020 03 27;129:108756. Epub 2019 Nov 27.

Department of Food Science and Technology, Federal University of Santa Catarina, Itacorubi, Florianópolis, SC 88034-001, Brazil. Electronic address:

The objective of this study was to investigate and quantify the composition phenolic, reducing capacity, the free radical scavenging activity, as well as, the anti-inflammatory effect evaluated against lipopolysaccharides-stimulated RAW264.7 macrophages through modulation of inflammatory mediators, in eight stingless bee honey types (Meliponinae) from southern Brazil. Stingless bee honey did not show to be cytotoxic at the tested concentrations (1-100 µM) and also reduced nitric oxide and the secretion of the pro-inflammatory cytokine in the inflamed macrophages. Two honey samples showed the ability to increase the secretion of anti-inflammatory cytokine (interleukin-10), suggesting a significant anti-inflammatory effect. All these findings indicate that stingless bee honey could be an important source of natural compounds presenting anti-inflammatory and antioxidant effect, which could would provide health benefits when included in the diet.
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http://dx.doi.org/10.1016/j.foodres.2019.108756DOI Listing
March 2020

Transbuccal delivery of benznidazole associated with monoterpenes: permeation studies and mechanistic insights.

Eur J Pharm Sci 2020 Feb 5;143:105177. Epub 2019 Dec 5.

Department of Pharmaceutical Sciences, Federal University of Santa Catarina, Campus Reitor João David Ferreira Lima, s/n - Trindade, Florianópolis, SC 88040-900, Brazil. Electronic address:

Benznidazole (BZN) represents the only drug currently available for the treatment of Chagas disease in most endemic countries. When administered orally, high doses are required due to its extensive hepatic metabolism and its toxicity represents the main reason for treatment withdrawals. Because of these complications, transbuccal administration of BZN was investigated. This route avoids the first-pass hepatic metabolism and presents high permeability, with direct access to the systemic circulation. BZN was applied on porcine buccal mucosa after pretreatment with pure eugenol, carvacrol or limonene. Thermal (DSC) and spectroscopic (FT-IR) analyzes were performed to investigate the mechanisms of drug absorption enhancement. The permeability coefficient values of BZN increased 2.6, 2.9 and 4.9-fold after pretreatment with eugenol, carvacrol and limonene, respectively. The lag time, in turn, was shortened in the pretreated samples. The DSC and FT-IR analyzes suggested that transport of BZN through the buccal mucosa is associated with log P and size of monoterpenes. Limonene, the most effective absorption enhancer, contributed to greater interaction with non-polar domains of the buccal epithelium. Overall, BZN showed to be efficiently transported through the buccal route, but in vivo pharmacokinetic studies should be performed to confirm these findings.
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http://dx.doi.org/10.1016/j.ejps.2019.105177DOI Listing
February 2020

Intestinal permeability enhancement of benzopyran HP1-loaded nanoemulsions.

Eur J Pharm Sci 2019 Jan 28;127:115-120. Epub 2018 Oct 28.

Institut Galien Paris-Sud, CNRS UMR 8612, Université Paris-Sud, 5 rue Jean Baptiste Clément, 92296 Châtenay-Malabry Cedex, France.

The benzopyran HP1, a compound isolated from Hypericum polyanthemum, has demonstrated significant opioid-mediated antinociceptive activity after its oral administration. Despite the pharmacological potential, the poor aqueous solubility limits the oral absorption of this compound. For this reason, HP1 has been alternatively incorporated in lipid-based drug delivery systems. Given that nanoemulsions showed higher antinociceptive action than the free compound in a previous report, in this study, the main objective was to investigate the intestinal transport mechanisms of this system. The Ussing chamber model and rat jejunum were selected for this purpose. The apparent permeability coefficient of HP1 increased approximately 5.3 times after its incorporation in nanoemulsions. Considering that the absorptive transport of HP1 was significantly higher than the secretory transport, the participation of active transporters was suggested. The amount of HP1 in the acceptor chamber was reduced during permeability assays performed at 4 °C, supporting the hypothesis that active transporters are involved in the intestinal transport of this compound. The amount of free fatty acids released from nanoemulsion was approximately 60% after 90 min, demonstrating that part of this system is disassembled before absorption. Nanoemulsion constituents would be able to form new structures with biological constituents, leading to a rapid solubilization of HP1. A mucoadhesion rate of 50% was achieved by nanoemulsion after 30 min, which would also contribute to explain the higher absorption of this system. The particle size of the nanoemulsion is also compatible with endocytosis-mediated transport. Taken together, these results suggest that nanoemulsions containing HP1 could be efficiently delivered to humans considering that different absorption mechanisms are exploited.
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http://dx.doi.org/10.1016/j.ejps.2018.10.024DOI Listing
January 2019

Vasorelaxant effect of standardized extract of Cecropia glaziovii Snethl encapsulated in PLGA microparticles: In vitro activity, formulation development and release studies.

Mater Sci Eng C Mater Biol Appl 2018 Nov 21;92:228-235. Epub 2018 Jun 21.

Laboratório de Farmacotécnica, Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Santa Catarina (UFSC), Florianópolis 88040-900, Brazil. Electronic address:

In this study, the standardized dry extract of C. glaziovii (SDE) provided a significant vasorelaxant effect after contractions induced by phenylephrine in rat aortic rings in an endothelium-dependent manner, confirming that endothelial factors are needed to stimulate this response. A vasorelaxation close to that of acetylcholine was achieved, justifying the development of new formulations for this plant material. In this context, microparticles were selected to encapsulate SDE and the double emulsion technique was considered because of the hydrophilic nature of plant material. Two experimental designs were applied. Firstly, the effect of formulation parameters on particle size, size distribution and encapsulation efficiency (EE) was evaluated. As low EE was achieved, the effect of the osmotic pressure of the external phase was evaluated in a second experimental design. The presence of the osmotic agent (NaCl) impacted positively on the EE and slower in vitro release profile was obtained, which is desired in controlled release systems. The formation of denser and less porous particle surface, which was identified by SEM analysis, contributes to explain these findings. Microstructures showed to be a promising delivery system for the C. glaziovii SDE considering that a sustained release was achieved.
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http://dx.doi.org/10.1016/j.msec.2018.06.046DOI Listing
November 2018

Cocrystallization as a novel approach to enhance the transdermal administration of meloxicam.

Eur J Pharm Sci 2018 Oct 20;123:184-190. Epub 2018 Jul 20.

Programa de Pós-Graduação em Farmácia, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-970, Brazil. Electronic address:

Despite its large effectiveness, the long-term oral administration of high doses of meloxicam (MLX) may lead to gastrointestinal events such as abdominal pain, diarrhea, dyspepsia, ulceration, hemorrhage, and gastrointestinal perforation. Moreover, the pH-dependent solubility of MLX makes the development of new oral formulations even more challenging. As an alternative to overcome these limitations, the transdermal delivery of this drug has been purposed. Although various physical and chemical approaches to enhance the absorption of MLX may be found in literature, the use of cocrystallization has not been reported so far. Cutaneous permeation of MLX and 1:1 meloxicam-salicylic acid cocrystal (MLX-SLC) were evaluated using Franz diffusion cells. Cocrystal was suspended in an aqueous solution and in a gel to evaluate the vehicle effect on permeation parameters. In aqueous medium, the cocrystallization showed to enhance the drug permeation coefficient from 1.38 to 2.15 × 10 cm/h. MLX-SLC generated supersaturation with respect to the drug during dissolution studies simulating the conditions in the Franz cell donor chamber. This greater amount of free drug in the solution could contribute to explain the higher transdermal absorption and shorter lag time of this system. In addition, the acidic coformer ionization led to a pH reduction from 7.4 to 5.8, which, in turn, provided an increase in the unionized species of the drug, enhancing its permeation rate. The gel containing cocrystals reduced MLX permeation rate significantly (P = 0.42 × 10 cm/h), which was attributed to its higher viscosity.
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http://dx.doi.org/10.1016/j.ejps.2018.07.038DOI Listing
October 2018

Effect of extrusion temperature and screw speed on properties of oat and rice flour extrudates.

J Sci Food Agric 2018 Jul 28;98(9):3427-3436. Epub 2018 Feb 28.

Department of Food Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.

Background: Whole oat and rice flours were mixed to develop instant flours by a high pressure and low mechanical shear extrusion process. The screw profile was designed aiming to obtain an infant food with gelatinized starch and high hydration ability. Response surface methodology was selected to study the impact of operating parameters such as temperature and screw speed (73-186 °C; 109-391 rpm) on physicochemical and pasting properties of the final extruded product. The main challenge of this study was to process high oats content, since they are characterized by high lipid and fiber content, which impact on material processing.

Results: The optimal response was achieved at 170 °C and 350 rpm. The optimal expansion ratio, bulk density, water absorption index, and water solubility index were 2.24, 289.65 kg m , 6.42 g g , and 4.75 g g respectively. Overall, both temperature and screw speed affected the responses studied, except for water absorption index (only screw speed affected this response). Although lipids from oats reduce the expansion ratio of extrudates compared with samples containing higher starch proportions, their lipids protect the starch granules from mechanical degradation when higher screw speed values are used. As a result, both ungelatinized and gelatinized starches may be found in extrudates, which was confirmed by pasting property analyses.

Conclusion: High oat content may be efficiently processed by optimizing the extruder conditions (temperature, screw speed, and profile), improving the nutritional properties of the final product. © 2017 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.8855DOI Listing
July 2018

Chitosan microencapsulation of the dispersed phase of an O/W nanoemulsion to hydrochlorothiazide delivery.

J Microencapsul 2017 Nov 10;34(7):611-622. Epub 2017 Sep 10.

a Post-graduation Program in Pharmaceutical Sciences, Quality Control Laboratory , Universidade Federal de Santa Catarina , Florianópolis , Brazil.

In view of biopharmaceutical limitations of hydrochlorothiazide (HCTZ), Trojan-type mucoadhesive systems were proposed, aiming to improve HCTZ pharmacological properties by modulating its release. Nanoemulsions were formed spontaneously by combining medium-chain triglycerides (Lipoid S75 and Pluronic F68) and high encapsulation efficiency was obtained. The mucoadhesive properties were provided by chitosan and microencapsulation of nanoemulsions in spray-dryer was successfully achieved by using Aerosil as wall material. The rapid redispersion of nanoemulsion in simulated fluids led to a fast and complete release of HCTZ in gastric medium. The pharmacodynamics of HCTZ was improved, extending the diuretic activity. Once a simple and low-energy method contributed to obtain stable mucoadhesive nanoemulsions, advantages in terms of production could also be achieved, allowing easy scaling up. This novel mucoadhesive Trojan particulate system of HCTZ showed to be a promising approach to overcome limitations in terms of absorption and consequently improve the therapeutic efficacy.
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http://dx.doi.org/10.1080/02652048.2017.1373155DOI Listing
November 2017

Self-Nanoemulsified Drug Delivery System of Hydrochlorothiazide for Increasing Dissolution Rate and Diuretic Activity.

AAPS PharmSciTech 2017 Oct 17;18(7):2494-2504. Epub 2017 Feb 17.

Post-graduation Program in Pharmaceutical Sciences, Quality Control Laboratory, Universidade Federal de Santa Catarina, J/K 207, 88040-900, Florianópolis, SC, Brazil.

Hydrochlorothiazide (HCTZ) is a class IV drug according to the Biopharmaceutical Classification System. This study aimed the development of self-nanoemulsifying drug delivery system (SNEDDS) for HCTZ as an approach to overcome the biopharmaceutical limitations. Pre-formulation screening and ternary phase diagrams were carried out to select the oil phase, the surfactant, and the co-surfactant as the amount of each constituent. The optimized formulations, with reduced amount of surfactant, and composed of medium chain triglycerides, Cremophor EL and Transcutol P did not affect the pH or show drug incompatibilities. The SNEDDS were stabilized by the nanoscale globules and high negative zeta potential. All the physicochemical characterization assays were performed in biorelevant media to better predict the in vivo performance. The enhanced dissolution rate of the SNEDDS reflected in the in vivo diuretic activity, presenting a natriuresis, kaliuresis, and chloriuresis at early stages and an increased volume of total urine compared with HCTZ alone. The designed SNEDDS produced an improvement in the pharmacodynamics due to high dissolution and probable inhibition of intestinal efflux protein by Cremophor EL. The use of SNEDDS demonstrated to be an efficient approach to modulate the absorption of HCTZ and drug therapeutics.
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http://dx.doi.org/10.1208/s12249-017-0735-zDOI Listing
October 2017

Lipid- and Polymer-Based Nanostructures for Cutaneous Delivery of Curcumin.

AAPS PharmSciTech 2017 Apr 26;18(3):920-925. Epub 2016 May 26.

Laboratório de Controle de Qualidade, Programa de Pós-Graduação em Farmácia, Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina (UFSC), Campus Universitário, Trindade, 88040-900, Florianópolis, SC, Brazil.

It is well-known that nanoencapsulation may overcome biopharmaceutical limitations of curcumin (CUR), but studies regarding the contribution of the vesicular nature of CUR-loaded nanoparticles on skin permeation are still scarce. Therefore, the effect of three colloidal systems (solid lipid nanoparticles (SLN), nanoemulsion (NE), and polymeric nanoparticles (NP)) on the control of cutaneous permeation of CUR was investigated in porcine ear skin/Franz diffusion cells. Colloidal suspensions were designed to present a similar particle size (±170 nm), narrow size distribution (PdI < 0.2), and high entrapment efficiency (>99%). Zeta potential values were -0.13, -9.68 and -36.7 mV for the CUR-loaded NP, SLN and NE, respectively. Nanoencapsulation resulted in a cumulative amount of CUR in the more superficial layers of the skin. NP significantly enhanced the compound retention in the epidermis, which was approximately 2.49- and 3.32-fold more than SLN and NE, respectively. The CUR levels into the dermis were significantly increased after treatment with NE, which may be associated with repulsion phenomena in surface skin. Therefore, a more superficial or deeper action of CUR on the skin may be obtained depending on nanostructure type. While NPs are more effective in upper skin layers, NE should be prioritized when a dermal action for the CUR is required.
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http://dx.doi.org/10.1208/s12249-016-0554-7DOI Listing
April 2017

Pharmacokinetics of Saquinavir Mesylate from Oral Self-Emulsifying Lipid-Based Delivery Systems.

Eur J Drug Metab Pharmacokinet 2017 Feb;42(1):135-141

Laboratório de Virologia Aplicada (Programa de Pós-Graduação em Farmácia), Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, 88040-900, Brazil.

Background And Objectives: Although lipid-based drug delivery systems have gained much importance in recent years due to their ability to improve the solubility and bioavailability of poorly soluble drugs, compartmental pharmacokinetic analyses have not been extensively explored. The oral pharmacokinetics of commercial liquid formulation and a developed semisolid system containing saquinavir mesylate (SQVM) were compared in Beagle dogs. A compartmental analysis after intravenous bolus administration of this drug (1 mg/kg) was also performed.

Method: Pharmacokinetic profiles were analyzed using both non-compartmental and compartmental approaches. Plasma concentration of the drug was determined by high-performance liquid chromatography/tandem mass spectrometry (LC/MS/MS).

Results: The disposition curve of SQVM given intravenously was better described by a three-compartment model. In contrast, plasma profiles obtained following the oral administration were fitted to a two-compartment model with lag time due to the fact that the distribution phase was masked by the absorption phase in these formulations.

Conclusion: The proposed semisolid lipid system was found to be a promising formulation for commercial purposes given the similarity of SQVM absorption rate to that from the commercial liquid formulation.
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http://dx.doi.org/10.1007/s13318-016-0321-xDOI Listing
February 2017

Adipose-Derived Stem Cells Decrease Bone Morphogenetic Protein Type 2-Induced Inflammation In Vivo.

J Oral Maxillofac Surg 2016 Mar 21;74(3):505-14. Epub 2015 Sep 21.

Professor, Department of Pharmaceutical Sciences, Federal University of Santa Catarina, Florianópolis, Brazil.

Purpose: Recombinant human bone morphogenetic protein type 2 (rhBMP-2) has been used to promote bone regeneration. In contrast, some reports have suggested rhBMP-2 does not provide advantages over autogenous bone grafting owing to the undesirable postoperative symptoms of this growth factor. Because the undesirable symptoms of rhBMP-2 are usually promoted by inflammation, this study evaluated the in vivo effect of human adipose-derived stem cells (ASCs) incorporated into polylactic co-glycolic acid (PLGA) scaffolds in decreasing the inflammatory response induced by a low dose of rhBMP-2.

Materials And Methods: PLGA scaffolds were characterized and loaded with rhBMP-2 1, 2.5, or 5 μg per scaffold (n = 6) and the in vitro released protein amounts were quantified at 7 hours and 1, 7, and 21 days after loading (n = 3). The muscle tissue of 6 beagles received the following treatments: PLGA, PLGA plus rhBMP-2 (2.5 μg), and PLGA plus rhBMP-2 plus ASCs (1 × 10(6) ASCs). The samples were evaluated 45 days after surgery. Statistical analyses were performed and the P value was set at .05.

Results: PLGA plus rhBMP-2 plus ASCs yielded the smallest number of inflammatory foci (P < .001) and giant cells (P < .001) and the largest number of angiogenesis sites (P < .001).

Conclusions: Human ASCs administered in vivo into PLGA scaffolds with a low dose of rhBMP-2 decrease tissue inflammation and increase angiogenesis in muscular sites.
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http://dx.doi.org/10.1016/j.joms.2015.09.006DOI Listing
March 2016

Novel perspectives in the tuberculosis treatment: Administration of isoniazid through the skin.

Int J Pharm 2015 Oct 28;494(1):463-70. Epub 2015 Aug 28.

Programa de Pós-Graduação em Farmácia (PGFAR), Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, 88040-900 Florianópolis, SC, Brazil.

Despite its high efficacy in anti-tuberculosis therapy, the oral administration of isoniazid (INH) may lead to poor patient compliance due to hepatotoxicity events. In this context, the transdermal administration of INH was evaluated, for the first time, since this route avoids hepatic first pass effect. INH was applied to porcine skin in Franz diffusion chambers alone and with 5% menthol, limonene or Transcutol(®). Infrared and DSC analyses were selected for mechanistic studies. The transdermal absorption of INH was sufficient to ensure a systemic therapeutic effect. Menthol was not able to improve the absorption of INH, but it increased the drug accumulation in skin compared to the control (1.4-fold). Transcutol(®) reduced permeation flux of INH (2.2-fold) and also increased the amount of drug retained in skin (1.7-fold). Limonene was the most effective excipient since it increased permeation flux of INH (1.5-fold) and lag time was greatly shortened (2.8-fold). DSC and FTIR analyses of limonene-treated skin suggest higher degree of disorder in lipid bilayers. Transdermal delivery of INH was positively correlated with logP of chemical enhancers. INH can be efficiently delivered by skin route and specific excipients may be selected depending on intended use.
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http://dx.doi.org/10.1016/j.ijpharm.2015.08.067DOI Listing
October 2015

In vitro and in vivo genotoxic evaluation of Bothrops moojeni snake venom.

Pharm Biol 2015 Jun 28;53(6):930-4. Epub 2014 Nov 28.

Laboratory of Mutagenesis, Universidade Católica Dom Bosco , Campo Grande - MS , Brazil .

Context: Bothrops moojeni Hoge (Viperidae) venom is a complex mixture of compounds with therapeutic potential that has been included in the research and development of new drugs. Along with the biological activity, the pharmaceutical applicability of this venom depends on its toxicological profile.

Objective: This study evaluates the cytotoxicity and genotoxicity of the Bothrops moojeni venom (BMV).

Material And Methods: The in vitro cytotoxicity and genotoxicity of a pooled sample of BMV was assessed by the MTT and Comet assay, respectively. Genotoxicity was also evaluated in vivo through the micronucleus assay.

Results: BMV displayed a 50% cytotoxic concentration (CC50) on Vero cells of 4.09 µg/mL. Vero cells treated with 4 µg/mL for 90 min and 6 h presented significant (p < 0.05, ANOVA/Newman-Keuls test) higher DNA damage than the negative control in the Comet assay. The lower DNA damage found after 6 h compared with the 90 min treatment suggests a DNA repair effect. Mice intraperitoneally treated with BMV at 10, 30, or 80 µg/animal presented significant genotoxicity (p < 0.05, ANOVA/Newman-Keuls test) in relation to the negative control after 24 h of treatment. Contrary to the in vitro results, no DNA repair seemed to occur in vivo up to 96 h post-venom inoculation at a dose of 30 µg/animal.

Discussion And Conclusion: The results show that BMV presents cyto- and genotoxicity depending on the concentration/dose used. These findings emphasize the importance of toxicological studies, including assessment of genotoxicity, in the biological activity research of BMV and/or in the development of BMV-derived products.
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http://dx.doi.org/10.3109/13880209.2014.950385DOI Listing
June 2015

Adipose-derived stem cells incorporated into platelet-rich plasma improved bone regeneration and maturation in vivo.

Dent Traumatol 2015 Feb 21;31(1):42-8. Epub 2014 Oct 21.

Bioscience and Biotechnology Post-Graduate Program, Universidade Federal de Santa Catarina, Florianópolis, Brazil.

Background/aim: Some cases of tooth loss related to dental trauma require bone-grafting procedures to improve the aesthetics before prosthetic rehabilitation or to enable the installation of dental implants. Bone regeneration is often a challenge and could be largely improved by mesenchymal stem cells therapy. However, the appropriate scaffold for these cells still a problem. This study evaluated the in vivo effect of human adipose-derived stem cells incorporated into autogenous platelet-rich plasma in bone regeneration and maturation.

Material And Methods: Adipose-derived stem cells were isolated from lipoaspirate tissues and used at passage 4. Immunophenotyping and multilineage differentiation of cells were performed and mesenchymal stem cells characteristics confirmed. Bicortical bone defects (10 mm diameter) were created in the tibia of six beagle dogs to evaluate the effect of adipose-derived stem cells incorporated into platelet-rich plasma scaffolds, platelet-rich plasma alone, autogenous bone grafts, and clot. Samples were removed 6 weeks postsurgeries and analyzed by quantification of primary and secondary bone formation and granulation tissue.

Results: Adipose-derived stem cells incorporated into platelet-rich plasma scaffolds promoted the highest bone formation (primary + secondary bone) (P < 0.001), the highest bone maturation (secondary bone) (P < 0.001), and the lowest amount of granulation tissue (P < 0.001).

Conclusions: Adipose-derived stem cells incorporated into platelet-rich plasma scaffolds promote more bone formation and maturation, and less granulation tissue in bone defects created in canine tibia. Therefore, platelet-rich plasma can be considered as a candidate scaffold for adipose-derived stem cells to promote bone regeneration.
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http://dx.doi.org/10.1111/edt.12134DOI Listing
February 2015

Enhancing the buccal mucosal delivery of peptide and protein therapeutics.

Pharm Res 2015 Jan 29;32(1):1-21. Epub 2014 Aug 29.

Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia.

With continuing advances in biotechnology and genetic engineering, there has been a dramatic increase in the availability of new biomacromolecules, such as peptides and proteins that have the potential to ameliorate the symptoms of many poorly-treated diseases. Although most of these macromolecular therapeutics exhibit high potency, their large molecular mass, susceptibility to enzymatic degradation, immunogenicity and tendency to undergo aggregation, adsorption, and denaturation have limited their ability to be administered via the traditional oral route. As a result, alternative noninvasive routes have been investigated for the systemic delivery of these macromolecules, one of which is the buccal mucosa. The buccal mucosa offers a number of advantages over the oral route, making it attractive for the delivery of peptides and proteins. However, the buccal mucosa still exhibits some permeability-limiting properties, and therefore various methods have been explored to enhance the delivery of macromolecules via this route, including the use of chemical penetration enhancers, physical methods, particulate systems and mucoadhesive formulations. The incorporation of anti-aggregating agents in buccal formulations also appears to show promise in other mucosal delivery systems, but has not yet been considered for buccal mucosal drug delivery. This review provides an update on recent approaches that have shown promise in enhancing the buccal mucosal transport of macromolecules, with a major focus on proteins and peptides.
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http://dx.doi.org/10.1007/s11095-014-1485-1DOI Listing
January 2015

Exploiting the buccal mucosa as an alternative route for the delivery of donepezil hydrochloride.

J Pharm Sci 2014 Jun 28;103(6):1643-51. Epub 2014 Mar 28.

Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, 3052, Australia; Laboratório de Virologia Aplicada, Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis-SC, 88040-900, Brazil.

The potential of the buccal mucosa as an alternative route for the systemic delivery of donepezil (DPZ) hydrochloride, and the impact of various skin penetration enhancers on DPZ buccal permeability, was assessed using an in vitro model. DPZ was applied to porcine buccal mucosa in modified Ussing chambers either alone (20 μg/mL) or with different treatment protocols of various enhancers including Azone® (AZ), deoxycholic acid (DA), polyethylene glycol (PEG) 400, and oleic acid (OA)-PEG 400. DPZ permeated the buccal mucosa very rapidly with a permeability coefficient of 35.6 ± 4.9 × 10(-6) cm/s, which was not significantly affected by AZ pretreatment. Coapplication of DA 0.6% (w/w), but not DA 0.01% (w/w), reduced the buccal permeation of DPZ (3.5-fold), and PEG 400 reduced the absorption of DPZ in a dose-dependent manner (1.6- and 18.0-fold reduction at 5% and 50%, w/w, PEG 400, respectively). Coapplication of a combination of OA 1% (v/w) and PEG 400 5% (w/w) further reduced DPZ permeability (5.5-fold), which was demonstrated to result from excipient-induced DPZ precipitation as assessed by light microscopy analysis. These results confirm the feasibility of a novel buccal delivery system for Alzheimer's disease, and suggest various approaches that may be exploited for controlled buccal delivery of DPZ.
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http://dx.doi.org/10.1002/jps.23950DOI Listing
June 2014

Antimutagenic and antiherpetic activities of different preparations from Uncaria tomentosa (cat's claw).

Food Chem Toxicol 2014 Apr 18;66:30-5. Epub 2014 Jan 18.

Laboratório de Virologia Aplicada, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, 88040-900 Florianópolis-SC, Brazil; Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, 88040-900 Florianópolis-SC, Brazil. Electronic address:

Uncaria tomentosa have been used to treat viral diseases such as herpes due to multiple pharmacological effects, but its therapeutic efficacy against this virus have not been reported yet. Thus, in vitro antiherpetic activity of hydroethanolic extract from barks, purified fractions of quinovic acid glycosides and oxindole alkaloids was evaluated by plaque reduction assay, including mechanistic studies (virucidal, attachment and penetration action). Once exposure to physical agents might lead to reactivation of the herpetic infection, antimutagenic effect (pre-, simultaneous and post-treatment protocols) was also evaluated by Comet assay. The antiherpetic activity from the samples under investigation seemed to be associated with the presence of polyphenols or their synergistic effect with oxindole alkaloids or quinovic acid glycosides, once both purified fractions did not present activity when evaluated alone. Inhibition of viral attachment in the host cells was the main mechanism of antiviral activity. Although both purified fractions displayed the lowest antimutagenic activity in pre and simultaneous treatment, they provided a similar effect to that of cat's claw hydroethanolic extract in post-treatment. Given that purified fractions may result in a reduced antiherpetic activity, the use of cat's claw hydroethanolic extract from barks should be prioritized in order to obtain a synergistic effect.
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http://dx.doi.org/10.1016/j.fct.2014.01.013DOI Listing
April 2014

Chitosan-decorated polystyrene-b-poly(acrylic acid) polymersomes as novel carriers for topical delivery of finasteride.

Eur J Pharm Sci 2014 Feb 19;52:165-72. Epub 2013 Nov 19.

Programa de Pós-Graduação em Química, Departamento de Química, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, 88040-900 Florianópolis, SC, Brazil. Electronic address:

In view of the fact that the oral administration of finasteride (FIN) has resulted in various undesirable systemic side effects, the topical application of polystyrene and poly(acrylic acid)-based polymersomes (underexplored system) was investigated. Undecorated PS139-b-PAA17 and PS404-b-PAA63 vesicles (C3 and C7, respectively) or vesicles decorated with chitosan samples of different molecular weight (C3/CS-oligo, C7/CS-oligo, C3/CS-37 and C7/CS-37) were prepared by the co-solvent self-assembly method and characterized by small-angle X-ray scattering,transmission electron microscopy and dynamic light scattering techniques. In vitro release experiments and ex vivo permeation using Franz diffusion cells were carried out (through comparison with hydroethanolic finasteride solution). The ideal system should provide high finasteride retention in the dermis and epidermis while allowing some control of the drug release. The particle size and in vitro release were negatively correlated with the permeation coefficient and skin retention in both the epidermis and dermis. The findings that the longest lag time was obtained for the hydroethanolic drug solution and lowest permeation for the systems able to release the drug faster support the hypothesis that nanostructured systems may be required to enhance the penetration and permeation of the drug. Chitosan-decorated polymersomes interacted more strongly with the skin components than non-decorated samples, probably due to the positive surface charge, which increased the FIN retention and reduced the lag time. C7 polymersomes decorated with chitosan were more appropriate for topical applications (high retention in the dermis and epidermis and controlled drug delivery).
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http://dx.doi.org/10.1016/j.ejps.2013.11.008DOI Listing
February 2014

Development and physicochemical characterization of saquinavir mesylate solid dispersions using Gelucire 44/14 or PEG 4000 as carrier.

Arch Pharm Res 2013 Sep 23;36(9):1113-25. Epub 2013 May 23.

Laboratório de Virologia Aplicada, Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, 88040-900, Brazil.

Solid dispersions of saquinavir mesylate containing either Gelucire® 44/14 or poly(ethylene glycol) (PEG) 4000, or mixtures of each carrier with Tween 80 or polyvinyl pyrrolidone (PVP) K30 were prepared in order to enhance the drug dissolution rate. These systems were prepared by the melting method and characterized by X-ray powder diffraction, microscopical techniques, and Raman spectroscopy aiming to establish a relationship between physicochemical and dissolution properties under different cooling conditions. Modifications in degree of crystalline order/disorder over time were observed in preparations with both carriers. Overall, formulations cooled and stored at -20 °C showed less variation in dissolution rates than those at 25 °C. Although Tween 80 has enhanced the known self-emulsifying properties of Gelucire® 44/14, its combination with PEG 4000 displayed miscibility problems. The addition of PVP K30 was not the most effective approach in enhancing the dissolution in early steps; however, the drug dissolution was stable after 7 days of storage at 25 °C. The combination of PEG 4000 and PVP K30 maintained the dissolution properties for 60 and 90 days at 25 °C/95% relative humidity and 40 °C/75% (f₂ values >50), respectively.
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http://dx.doi.org/10.1007/s12272-013-0142-2DOI Listing
September 2013

Addition of bone morphogenetic protein type 2 to ascorbate and β-glycerophosphate supplementation did not enhance osteogenic differentiation of human adipose-derived stem cells.

J Appl Oral Sci 2012 Nov-Dec;20(6):628-35

Department of Dentistry, Federal University of Santa Catarina, Florianópolis, SC, Brazil.

Unlabelled: Bone morphogenetic protein type 2 (BMP-2) is a potent local factor, which promotes bone formation and has been used as an osteogenic supplement for mesenchymal stem cells.

Objectives: This study evaluated the effect of a recombinant BMP-2 as well as the endogenous BMP-4 and BMP-7 in the osteogenic differentiation of adipose-derived stem cells (ASCs) in medium supplemented with ascorbate and β-glycerophosphate.

Material And Methods: Human ASCs were treated with osteogenic medium in the presence (ASCs+OM+BMP-2) or absence (ASCs+OM) of BMP-2. The alkaline phosphatase (ALP) activity was determined and the extracellular matrix mineralization was evaluated by Von Kossa staining and calcium quantification. The expressions of BMP-4, BMP-7, Smad1, Smad4, and phosphorylated Smad1/5/8 were analyzed by western blotting. Relative mRNA expressions of Smad1, BMP receptor type II (BMPR-II), osteonectin, and osteocalcin were evaluated by qPCR.

Results: ASCs+OM demonstrated the highest expression of BMP-4 and BMP-7 at days 21 and 7, respectively, the highest levels of BMPR-II mRNA expression at day 28, and the highest levels of Smad1 mRNA at days 14 and 28. ASCs+OM+BMP-2 demonstrated the highest levels of Smad1 mRNA expression at days 1, 7, and 21, the highest expression of Smad1 at day 7, the highest expression of Smad4 at day 14, the highest ALP activity at days 14 and 21, and expression of phosphorylated Smad1/5/8 at day 7. ASCs+OM and ASCs+OM+BMP2 showed similar ALP activity at days 7 and 28, similar osteonectin and osteocalcin mRNA expression at all time periods, and similar calcium depositions at all time periods.

Conclusions: We concluded that human ASCs expressed endogenous BMP-4 and BMP-7. Moreover, the supplementation of ASCs with BMP-2 did not increase the level of osteogenic markers in the initial (ALP activity), intermediate (osteonectin and osteocalcin), or final (calcium deposition) phases, suggesting that the exogenous addition of BMP-2 did not improve the in vitro osteogenesis process of human ASCs.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3881851PMC
http://dx.doi.org/10.1590/s1678-77572012000600007DOI Listing
April 2013

Effect of freezing and type of mucosa on ex vivo drug permeability parameters.

AAPS PharmSciTech 2011 Jun 4;12(2):587-92. Epub 2011 May 4.

Laboratório de Virologia Aplicada, Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, Brazil.

The porcine esophageal mucosa has been proposed as a substitute for the buccal mucosa barrier on ex vivo permeability studies mainly due to its large surface area as well as its easier preparation. Therefore, this study compared the ex vivo permeability parameters of two drugs (carmabazepine (CBZ) and triamcinolone acetonide (TAC)) with different permeabilities and physicochemical properties through buccal and esophageal mucosae using a Franz diffusion cell system and HPLC as detection method. The freezing effects on drug permeability parameters were also evaluated by comparing them when fresh and frozen tissues were used. The barrier properties were not affected by the freezing process since the obtained parameters for both drugs were similar in frozen and fresh tissues (buccal and esophageal mucosae). However, an increase of CBZ retention was shown in frozen tissues. Fresh and frozen esophageal mucosae provided higher permeation of TAC than on buccal mucosae while the obtained permeability parameters for CBZ were similar on both mucosae. According to our results, porcine esophageal mucosa could be used as a substitute for buccal mucosa on ex vivo studies involving CBZ but not TAC. Frozen tissues could be used as substitute for fresh tissues in both cases. However, any substitution should be done with care and only if previous tests were performed, because the results could differ depending on the tested drug.
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http://dx.doi.org/10.1208/s12249-011-9621-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3134646PMC
June 2011

Evaluation of antirotavirus activity of flavonoids.

Fitoterapia 2010 Dec 24;81(8):1142-6. Epub 2010 Jul 24.

Laboratório de Virologia Aplicada, Departamento de Microbiologia, Imunologia e Parasitologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Trindade, Florianópolis, SC 88.040-970, Brazil.

Flavonoids are dietary components and the most ubiquitous phenolic compounds found in nature, showing a range of pharmacological activities including antiviral action. This study describes the antiviral screening of 60 different flavones and flavonols against human rotavirus (Wa-1 strain) as well as their cytotoxicity in MA104 cells. Cytotoxicity was investigated by cell morphology assessment and antirotavirus activity by cytopathic effect inhibition. Results were expressed as CC(50) and IC(50), respectively, in order to calculate the selectivity index (SI = CC(50)/IC(50)) of each compound. Structure-activity relationships (SAR) were proposed based on antirotavirus activity.
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http://dx.doi.org/10.1016/j.fitote.2010.07.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7126014PMC
December 2010

Evaluation of the transdermal permeation of different paraben combinations through a pig ear skin model.

Int J Pharm 2010 May 13;391(1-2):1-6. Epub 2010 Feb 13.

Laboratório de Virologia Aplicada, Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, 88040-900 Florianópolis, SC, Brazil.

Although parabens have several features of ideal preservatives, different studies have shown that they may affect human health due to their estrogenic activity. Therefore, various strategies have been applied to reduce their skin penetration. However, the effect of paraben combinations on transdermal permeation has not yet been investigated. Thus, the objective of this study was to evaluate paraben permeation in pig ear skin using a Franz diffusion cell system with capillary electrophoresis detection, in order to identify which paraben combinations (defined by a factorial design) have the lowest skin permeation. The permeation of isolated parabens was also evaluated and the permeation characteristics, obtained by the Moser model, confirmed that lipophilicity and molecular weight may influence the systemic absorption of these compounds. In previous tests using isolated parabens, methyl and ethyl parabens presented greater retention in the epidermis compared to the dermis, while propyl and butyl parabens had similar retention profiles in these layers. An increase in ethanol concentration and experimental time promoted greater parabens retention in the dermis compared to the epidermis. The binary combinations of methyl and ethyl parabens as well as of methyl and propyl parabens (added to several cosmetic products in order to increase the antimicrobial spectrum) reduced significantly their permeation rates through pig ear skin (with the exception of EP), probably due to the high retention of these parabens in the epidermis and dermis.
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http://dx.doi.org/10.1016/j.ijpharm.2010.02.006DOI Listing
May 2010