Juliana Marchetti - Academia.edu (original) (raw)

Papers by Juliana Marchetti

Ursolic acid is a promising candidate for treatment of Chagas disease; however it has low aqueous... more Ursolic acid is a promising candidate for treatment of Chagas disease; however it has low aqueous solubility and intestinal absorption, which are both limiting factors for bioavailability. Among the strategies to enhance the solubility and dissolution of lipophilic drugs, solid dispersions are growing in popularity. In this study, we employed a mixture of the surfactants poloxamer 407 with sodium caprate to produce a solid dispersion containing ursolic acid aimed at enhancing both drug dissolution and in vivo trypanocidal activity. Compared to the physical mixture, the solid dispersion presented higher bulk density and smaller particle size. Fourier Transform Infrared Spectroscopy results showed hydrogen bonding intermolecular interactions between drug and poloxamer 407. X-ray diffractometry experiments revealed the conversion of the drug from its crystalline form to a more soluble amorphous structure. Consequently, the solubility of ursolic acid in the solid dispersion was increased and the drug dissolved in a fast and complete manner. Taken together with the oral absorption-enhancing property of sodium caprate, these results explained the increase of the in vivo trypanocidal activity of ursolic acid in solid dispersion, which also proved to be safe by cytotoxicity evaluation using the LLC-MK2 cell line. Uniterms: Ursolic acid/trypanocidal activity. Chaga's Disease/treatment. Solid dispersions/dissolution. Poloxamer 407. Sodium caprate. Unitermos: Ácido ursólico/atividade tripanocida. Doença de Chagas/tratamento. Tensoativos. Dispersões sólidas/dissolução. Poloxamer 407. Caproato de sódio.

Potential of stratum corneum lipids liposomes for the topical delivery of 5-aminolevulinic acid i... more Potential of stratum corneum lipids liposomes for the topical delivery of 5-aminolevulinic acid in Title: photodynamic therapy of skin cancer. The manuscript "Stratum corneum lipids liposomes from the topical delivery of 5-aminolevulinic acid in photodynamic therapy of skin cancer: preparation and in vitro permeation study was revised based on referees suggestion. The changes are listed below: 1-Dr Jose Parra: We made in vitro retention experiments using tape-stripping method. We measured 5-ALA retained in SC and rest of epidermis + dermis. These results were very interesting because proved that 5-ALA was delivered preferencialy to the epidermis without SC + dermis, which is desirable for skin cancer treatment, ie the drug was delivery and retained in the skin tissue where skin cancer takes place. 2-Dr Arto Urtti The explanation above answers part of Dr Urtti's major comments. We used formalin (0.01% w/w) to preserve acceptor solution and the skin during in vitro experiment...

Materials Science and Engineering: C, 2021

Glioblastoma multiforme (GBM) is a first primary Central Nervous System tumor with high incidence... more Glioblastoma multiforme (GBM) is a first primary Central Nervous System tumor with high incidence and lethality. Its treatment is hampered by the difficulty to overcome the blood-brain barrier (BBB) and by the non-specificity of chemotherapeutics to tumor cells. This study was based on the development characterization and in vitro efficacy of folate-modified TPGS transfersomes containing docetaxel (TF-DTX-FA) to improve GBM treatment. TF-DTX-FA and unmodified transfersomes (TF-DTX) were prepared through thin-film hydration followed by extrusion technique and characterized by physicochemical and in vitro studies. All formulations showed low particles sizes (below 200 nm), polydispersity index below 0.2, negative zeta potential (between -16.75 to -12.45 mV) and high encapsulation efficiency (78.72 ± 1.29% and 75.62 ± 0.05% for TF-DTX and TF-DTX-FA, respectively). Furthermore, cytotoxicity assay of TF-DTX-FA showed the high capacity of the nanocarriers to reduce the viability of U-87 MG in both 2D and 3D culture models, when compared with DTX commercial formulation and TF-DTX. In vitro cellular uptake assay indicated the selectivity of transfersomes to tumoral cells when compared to normal cells, and the higher ability of TF-DTX-FA to be internalized into 2D U-87 MG in comparison with TF-DTX (72.10 and 62.90%, respectively, after 24 h). Moreover, TF-DTX-FA showed higher permeability into 3D U-87 MG spheroid than TF-DTX, suggesting the potential FA modulation to target treatment of GBM.

Colloids and Surfaces B: Biointerfaces, 2020

Prostate cancer is the second cause of cancer death in men worldwide. Docetaxel (DTX), an antimit... more Prostate cancer is the second cause of cancer death in men worldwide. Docetaxel (DTX), an antimitotic drug, is widely used for the treatment of metastatic prostate cancer patients. Taxotere ® is a commercial DTX formulation. It contains a polysorbate 80 surfactant to improve DTX aqueous solubility, which has been associated with hypersensitivity reactions in patients. Liposomes have been used as promising delivery systems for a range of hydrophobic drugs, such as DTX, offering improved drug water solubility and biocompatibility, without compromising its anticancer activity. Herein, DTX-loaded liposomes were developed using the Box-Behnken factorial design. The optimized formulation was nano-sized, homogenous in size (67.47 nm) with high DTX encapsulation efficiency (99.95%). The encapsulated DTX was in a soluble amorphous state, which was slowly released. Next, to increase the liposomes selectivity to prostate cancer cells, cetuximab, an anti-EGFR monoclonal antibody. was successfully conjugated to the surface of liposomes, without compromising cetuximab protein structure and stability. As expected, our results showed higher cellular uptake and toxicity of immunoliposomes, compared to non-targeted liposomes, in DU145 (EGFRoverxpressing) prostate cancer cells. To the best of our knowledge, this is the first report of engineering EGFR-targeted liposomes to enhance the selectivity of DTX delivery to EGFR-positive prostate cancer cells.

Revista Brasileira de Medicina de Família e Comunidade, 2018

Objetivo: Este estudo transversal visa analisar comparativamente as prescrições de medicamentos p... more Objetivo: Este estudo transversal visa analisar comparativamente as prescrições de medicamentos provenientes da atenção básica tradicional (Unidades Básicas de Saúde - UBS) com as da Estratégia de Saúde da Família (ESF). Métodos: Foram incluídas 1053 prescrições, alocadas em dois grupos: 932 provenientes de UBS e 121 da ESF. Tais prescrições foram analisadas de acordo com a adequação aos itens legalmente exigidos e aos indicadores de qualidade (presença de antimicrobianos, presença de injetáveis, uso da denominação oficial, uso da relação de medicamentos essenciais, média de medicamentos prescritos). Resultados: As prescrições da ESF se mostraram estatisticamente mais completas quanto à presença do endereço do prescritor (82,6% UBS, 96,7% ESF), à ausência de rasuras (90,3% UBS, 96,7% ESF) e ao cumprimento dos aspectos legais exigidos referentes ao uso do medicamento, sendo eles: forma farmacêutica (70,7% UBS, 80,2% ESF), dose (70,9% UBS, 79,3% ESF), posologia (63,0% UBS, 75,2% ESF),...

Materials Science and Engineering: C, 2017

Poly-epsilon-caprolactone nanoparticles enhance ursolic acid in vivo efficacy against Trypanosoma... more Poly-epsilon-caprolactone nanoparticles enhance ursolic acid in vivo efficacy against Trypanosoma cruzi infection

AAPS PharmSciTech, 2017

Over a hundred years after the discovery of Chagas disease, this ailment continues to affect thou... more Over a hundred years after the discovery of Chagas disease, this ailment continues to affect thousands of people. For more than 40 years, only two drugs have been available to treat it. Ursolic acid is a naturally occurring terpene that has shown a good trypanocidal action. However, the hydrophobicity of this compound presents a challenge for the development of proper delivery systems. Nanostructured systems are a prominent in delivering lipophilic drugs. Thus, a nanoemulsion containing ursolic acid was developed and had its trypanocidal activity and cytotoxicity evaluated. Pseudo-ternary phase diagrams and hydrophilic-lipophilic balance (HLB) system were used in the development. The system was stable throughout 90 days of testing, as evidenced by turbidimetry analysis and measurements of the droplet size (57.3 nm) and polydispersity index (0.24). Fourier transform infrared spectroscopy and mass spectrometry evidenced drug's integrity in the formulation. An in vitro dissolution profile showed 75% of ursolic acid release after 5 min from the nanoemulsion into the alkaline dissolution medium, while only 20% could be released from a physical mixture after 2 h. Trypanocidal activity and cytotoxicity were evaluated on the CL Brener strain and LLC-MK2 (monkey kidney) fibroblast by chlorophenol red-β-Dgalactoside (CPRG) method. Biological studies showed that the developed formulation was nontoxic and effective against replicant forms of the parasite. A stable and efficient nanoemulsion could be developed to improve the delivery of a promising drug to treat a threatening illness such as Chagas disease.

Nanobiomaterials in Drug Delivery, 2016

Abstract siRNA has recently emerged as a potential therapeutic tool for the treatment of a variet... more Abstract siRNA has recently emerged as a potential therapeutic tool for the treatment of a variety of human diseases, such as viral infection, cancer, cardiovascular and inflammatory disorders. Briefly, siRNAs are double-stranded RNAs formed by 21-23 nucleotides that are able to bind to and trigger the degradation of specific target messenger RNAs (mRNAs) through the silencing induced by the RNA-induced silencing complex. Compared with conventional therapeutics, it affords high specificity, resulting in improved efficacy and decreased side effects. However, many hurdles hamper the effective clinical application, including low intracellular delivery and poor in vivo stability. These drawbacks can be improved by the use of drug delivery systems as non-viral carriers of siRNA, which present important advantages over viral carriers, particularly the lower immunogenicity. Lipid nanoparticles are the most commonly reported type of drug delivery system for siRNA. They consist of vesicular systems, with an inner aqueous cavity, where siRNA can be loaded, surrounded by a lipid bilayer. This chapter will focus on the efforts that have been carried out to deliver siRNA loaded in lipid nanoparticles, highlighting the advantages, disadvantages, applications, clinical relevance, and future perspectives.

Bollettino chimico farmaceutico, 1999

Many workers have attempted to determine the bioavailability of pharmaceutical formulations, whic... more Many workers have attempted to determine the bioavailability of pharmaceutical formulations, which is important to assure the efficacy and safety of medications. In the present study, we investigated the bioavailability of five formulations of the combination of 0.8% trimethoprim (TMP) and 4% sulfamethoxazole (SMZ) (co-trimoxazole) as a suspension, containing different types of thickness agents. The blood levels of a single oral dose administered to rats were compared. Bioavailability was determined by comparing the time to peak concentration (Tmax), peak serum concentration (Cmax), total area under the concentration time curve (AUC) and the elimination rate constant (Kel). Analysis of the pharmacokinetic parameters of SMZ showed significant differences between the formulations, indicating that the absorption of SMZ was affected by thickness type. The calculated bioavailabilities of oral TMP and SMZ were 381, 558, 695, 480, 559 and 554 micrograms/mL, respectively, and the preparatio...

Journal of Colloid Science and Biotechnology, 2013

ABSTRACT All-trans retinoic acid has been used in various therapies for treating acne, photoaging... more ABSTRACT All-trans retinoic acid has been used in various therapies for treating acne, photoaging, psoriasis, keratinization disorders, acute promyelocytic leukemia, Kaposi's sarcoma, actinic keratoses and prevention and treatment of skin cancer. However, this drug promotes local irritation reactions that limit its topical use. Thus, the purpose of this study was to optimize retinoic acid therapy with the use of microparticles retinoic acid microparticles using PLA and PLGA were prepared and characterized. Skin penetration and skin irritation experiments were carried out. As results, PLGA microparticles presented high encapsulation efficiency (91%) and better release behavior than PLA microparticles. In vitro retention studies showed that PLGA microparticles increased the retinoic acid concentration in viable skin when compared to the control (non-microencapsulated retinoic acid). As result of a skin irritation study in mice, it was observed that there was a significant reduction of irritation associated with retinoic acid topical therapy when PLGA microparticles were used. Therefore, PLGA microparticles containing all-trans retinoic acid may be a viable alternative for decreasing the skin irritation produced by the drug.

International Journal of Pharmaceutics, 1999

Thermoreversible gels may be used in delivery systems which require a sol-gel transition at body ... more Thermoreversible gels may be used in delivery systems which require a sol-gel transition at body temperature. The influence of the addition of lecithin, a permeation enhancer, on the rheological and in vitro permeation properties of poloxamer 407 gels was investigated. Light microscopy and rheological parameters were used to characterize the microscopic structure of the formulations which showed non Newtonian behaviour, pseudoplastic flow with a yield value. Increased concentrations of lecithin increased the thixotropy, yield value, apparent viscosity, and the gelation temperature of the gels. Light microscopy showed the formation of micellar structures by the addition of lecithin, which may account for changes in rheological properties. In vitro permeation of a model drug, triamcinolone acetonide, was decreased when the lecithin concentration was increased. The presence of lecithin in the poloxamer gel improved the characteristics for topical drug delivery.

$Research paper thumbnail of Determinação de heparina fracionada em preparações farmacêuticas utilizando turbidimetria$

Química Nova, 2011

Recebido em 17/7/10; aceito em 5/12/10; publicado na web em 29/3/11 DETERMINATION OF FRACTIONATED... more Recebido em 17/7/10; aceito em 5/12/10; publicado na web em 29/3/11 DETERMINATION OF FRACTIONATED HEPARIN IN PHARMACEUTICAL DOSAGE FORMS USING TURBIDIMETRY. A turbidimetric method has been used for quantification of fractionated heparin (FH) in pharmaceutical dosage. The UV detection at two wavelengths (290 and 500 nm) showed a significant increase in sensitivity of the method, specificity, and linearity to range 5.0-50.0 μg mL-1 and 50.0-200.0 μg mL-1 , respectively (r < 0.99). At both wavelengths, the method was precise (inter-assay CV < 5.0%, and intra-assay CV < 3.0%), accurate (maximum deviation of ± 12%), and robust to the parameters evaluated. Turbidimetry proved to be easy, inexpensive and relatively fast. The results obtained attest to the reliability of the method.

International Journal of Pharmaceutics, 2006

Sophisticated delivery systems, such as nanoparticles, represent a growing area in biomedical res... more Sophisticated delivery systems, such as nanoparticles, represent a growing area in biomedical research. Nanoparticles (Np) were prepared using a solvent emulsion evaporation method (SEEM) to load zinc(II) phthalocyanine (ZnPc). Np were obtained using poly (d,l latic-co-glycolic acid) (PLGA). ZnPc is a second generation of photoactive agents used in photodynamic therapy. ZnPc loaded PLGA nanoparticles were prepared by SEEM, characterized and available in cellular culture. The process yield and encapsulation efficiency were 80 and 70%, respectively. The nanoparticles have a mean diameter of 285 nm, a narrow size distribution with polydispersive index of 0.12, smooth surface and spherical shape. ZnPc loaded nanoparticles maintains its photophysical behavior after encapsulation. Photosensitizer release from nanoparticles was sustained with a moderate and burst effect of 15% for 3 days. The photocytotoxicity of ZnPc loaded PLGA Np was evaluated on P388-D1 cells what were incubated with ZnPc loaded Np (5 M) by 6 h and exposed to red light (675 nm) for 120 s, and light dose of 30 J/cm 2. After 24 h of incubation, the cellular viability was determined, obtaining 61% of cellular death. All the physical-chemical, photophysical and photobiological measurements performed allow us conclude that ZnPc loaded PLGA nanoparticles is a promising drug delivery system for photodynamic therapy.

Colloids and surfaces. B, Biointerfaces, 2014

Although hydrophilic small molecule drugs are widely used in the clinic, their rapid clearance, s... more Although hydrophilic small molecule drugs are widely used in the clinic, their rapid clearance, suboptimal biodistribution, low intracellular absorption and toxicity can limit their therapeutic efficacy. These drawbacks can potentially be overcome by loading the drug into delivery systems, particularly liposomes; however, low encapsulation efficiency usually results. Many strategies are available to improve both the drug encapsulation efficiency and delivery to the target site to reduce side effects. For encapsulation, passive and active strategies are available. Passive strategies encompass the proper selection of the composition of the formulation, zeta potential, particle size and preparation method. Moreover, many weak acids and bases, such as doxorubicin, can be actively loaded with high efficiency. It is highly desirable that once the drug is encapsulated, it should be released preferentially at the target site, resulting in an optimal therapeutic effect devoid of side effects...

Journal of Drug Delivery, 2011

Nitric oxide (NO) is a promising pharmaceutical agent that has vasodilative, antibacterial, and t... more Nitric oxide (NO) is a promising pharmaceutical agent that has vasodilative, antibacterial, and tumoricidal effects. To study the complex and wide-ranging roles of NO and to facilitate its therapeutic use, a great number of synthetic compounds (e.g., nitrosothiols, nitrosohydroxyamines, N-diazeniumdiolates, and nitrosyl metal complexes) have been developed to chemically stabilize and release NO in a controlled manner. Although NO is currently being exploited in many biomedical applications, its use is limited by several factors, including a short half-life, instability during storage, and potential toxicity. Additionally, efficient methods of both localized and systemicin vivodelivery and dose control are needed. One strategy for addressing these limitations and thus increasing the utility of NO donors is based on nanotechnology.

Powder Technology, 2014

ABSTRACT Ursolic acid is a molecule with several therapeutic applications not yet commercially ex... more ABSTRACT Ursolic acid is a molecule with several therapeutic applications not yet commercially explored because of its bioavailability-limiting water insolubility. To avoid this drawback, solid dispersions containing ursolic acid have been employed to increase water solubility. The influence of hydrophilic carriers, PEG 6000 and Poloxamer 407, and the method of preparation, fusion and solvent, were studied for ursolic acid in this work. The solid dispersions and physical mixtures were characterized by particle size, scanning electron microscopy, fourier transform infrared spectroscopy, X-ray diffractometry, differential scanning calorimetry, hot stage microscopy, water solubility and dissolution profile. Results showed that both methods and polymers used for solid dispersion preparation resulted in homogeneous powders, but the surfactant Poloxamer 407 enhanced the ursolic acid solubility in solid dispersions better than PEG 6000. With Poloxamer 407, both methods enabled complete dissolution of ursolic acid in phosphate buffer; however the solid dispersion showed higher solubility when prepared by the solvent method compared to the fusion method, 689.47 μg/mL and 328.52 μg/mL, respectively. For comparison, the physical mixture solubility was 248.17 μg/mL. The better results achieved with the solvent method were attributed to smaller particle size, amorphic conversion of ursolic acid from its less soluble crystalline state and hydrogen bond formation between drug and carrier, whereas there was a polymorphic change caused by the fusion method. Results indicated that the solid dispersion prepared by the solvent method is an adequate approach to increasing ursolic acid solubility and dissolution, a very important step toward the development of a pharmaceutical dosage form containing ursolic acid.

Powder Technology, 2013

Poorly water soluble drugs tend to have low bioavailability, however, this can be improved by sev... more Poorly water soluble drugs tend to have low bioavailability, however, this can be improved by several methods. One of the most promising strategies is the employment of solid dispersions to increase water solubility and enhance oral bioavailability of these drugs. Nonetheless, the mechanisms of solid dispersion formation may influence the solid-state characteristics and thus the dissolution profile. In this study, rotary evaporation and spray-drying solvent evaporation techniques were used to produce solid dispersions of the anti-allergenic loratadine, a class II drug in the Biopharmaceutical Classification System, with the hydrophilic carrier polyvinylpyrrolidone K-30. Thermogravimetry, differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, particle size distribution by light scattering, solubility at different pHs, and dissolution profile experiments were carried out to evaluate the solid dispersions and physical mixtures. Results showed an increase in solubility, especially in acid medium, where the drug is protonated, and an enhancement in dissolution profiles, following first order kinetic, of solid dispersions manufactured by both the rotary evaporation and the spray-drying methods. Both methods proved to be equally adequate, when compared to physical mixtures. This is a consequence of particle size reduction, increased wettability due to intimate contact of the drug with the hydrophilic matrix, increased surface area, and the conversion of the crystalline to the amorphous state, which proved to be stable after 6 months at room temperature.

Molecular Crystals and Liquid Crystals, 2003

Layered double hydroxides (LDHs) can be structurally described as the stacking of positively char... more Layered double hydroxides (LDHs) can be structurally described as the stacking of positively charged layers with hydrated anions intercalated in the interlamellar domain. LDHs are a class of materials represented by the general formula: [{\rm M}_{1-{\rm x}}^{2+} {\rm M}_{\rm x}^{3+} ({\rm OH}){}_2] {\rm A}_{{\rm x/m}}^{{\rm m}-} \cdot {\rm nH}_2 {\rm O} where: M 2+ is a bivalent cation; M 3+

Journal of Physics and Chemistry of Solids, 2004

Layered double hydroxides (LDHs) present a potential application in medicine, as matrices, when i... more Layered double hydroxides (LDHs) present a potential application in medicine, as matrices, when intercalated with organic anions of pharmaceutical interest. Once encapsulated, the drug can be released at a rate, depending on the pH of the solution, which may be due to ...