Juliana Maldonado Marchetti
University of São Paulo
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Featured researches published by Juliana Maldonado Marchetti.
Colloids and Surfaces B: Biointerfaces | 2014
Josimar O. Eloy; Marina Claro de Souza; Raquel Petrilli; Juliana Palma Abriata Barcellos; Robert J. Lee; Juliana Maldonado Marchetti
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. For this purpose, targeted and triggered delivery approaches are available. The rapidly increasing knowledge of the many overexpressed biochemical makers in pathological sites, reviewed herein, has enabled the development of liposomes decorated with ligands for cell-surface receptors and active delivery. Furthermore, many liposomal formulations have been designed to actively release their content in response to specific stimuli, such as a pH decrease, heat, external alternating magnetic field, ultrasound or light. More than half a century after the discovery of liposomes, some hydrophilic small molecule drugs loaded in liposomes with high encapsulation efficiency are available on the market. However, targeted liposomes or formulations able to deliver the drug after a stimulus are not yet a reality in the clinic and are still awaited.
Journal of Controlled Release | 2000
Fernanda Scarmato De Rosa; Juliana Maldonado Marchetti; José Antônio Thomazini; Antonio C. Tedesco; Maria Vitória Lopes Badra Bentley
Topical application of 5-aminolevulinic acid (5-ALA) followed by light irradiation is a new concept of photodynamic therapy (PDT) of skin cancers. 5-ALA is a prodrug that can be converted by the heme biosynthetic pathway into protoporphyrin IX, an effective photosensitizer. In the present work we propose the enhancement of 5-ALA-induced protoporphyrin IX accumulation by dimethylsulphoxide (DMSO) and ethylenediamine-tetraacetic acid disodium salt (EDTA). The presence of 20% DMSO (w/w) in oil-in-water emulsions increased the in vitro permeation of 5-ALA through hairless mouse skin. In vivo studies demonstrated a significant increase in the amount of protoporphyrin IX extracted from healthy hairless mouse skin after 3 h treatment with an oil-in-water emulsion containing 10% 5-ALA (w/w), 3% EDTA (w/w) and 20% DMSO (w/w). By confocal scanning laser microscopy imaging, an observed increase in red fluorescence, at 476 nm excitation and emission detected longer than 590 nm, in skin that had received this treatment, was attributed to protoporphyrin IX accumulation. Although no effect of EDTA on short-term protoporphyrin IX accumulation in skin was detected, this chelator could protect 5-ALA from decomposition during prolonged topical administration. The results obtained indicate that association of 5-ALA, EDTA and 20% DMSO may enhance the delivery of 5-ALA to the skin in the topical PDT.
Journal of Controlled Release | 2003
Fernanda Scarmato De Rosa; Antonio C. Tedesco; Renata Fonseca Vianna Lopez; Maria Bernadete Riemma Pierre; Norbert Lange; Juliana Maldonado Marchetti; Jeane C. G. Rotta; Maria Vitória Lopes Badra Bentley
In photodynamic therapy (PDT), 5-aminiolevulinic acid (5-ALA) applied topically is converted, via the heme cycle, into protoporphyrin IX (PpIX), a photosensitizing agent, which upon excitation with light can induce tumor destruction. Due to its hydrophilic and zwitterionic characteristics, 5-ALA has limited penetration into the skin. More lipophilic 5-ALA ester derivatives are expected to cross stratum corneum more easily than 5-ALA. According to the determination of the partition coefficients of 5-ALA methyl, n-butyl, n-hexyl and n-octyl esters, these compounds showed an increased affinity to the SC, with 5-ALA hexyl ester and 5-ALA-octyl ester having the highest partition coefficients. Our in vitro skin permeation studies demonstrated an increased permeated amount for hexyl-ALA after 6 h of incubation, compared to other esters and 5-ALA. After 6 h, more 5-ALA-hexyl ester and -octyl ester were retained at viable epidermis and dermis than 5-ALA. According to these results, and considering that the conversion of 5-ALA into PpIX occurs preferentially in epidermis, it can be supposed that topical use of ester derivatives with longer chains (C(6) or C(8)) is an interesting proposal to optimize topical 5-ALA-PDT
International Journal of Pharmaceutics | 2001
D.J.A Netz; P Sepulveda; V.C Pandolfelli; A.C.C Spadaro; J.B Alencastre; Maria Vitória Lopes Badra Bentley; Juliana Maldonado Marchetti
Hydroxyapatite (HA) ceramic in a porous configuration is suggested as a drug release system. A new technique for the production of this material, based on the foaming of suspensions and in situ polymerization (gelcasting method), resulted in a material whose characteristics are likely to make it useful as an implantable drug delivery system. Three batches of HA ceramic with different porosities were characterized by X-ray diffraction and scanning electron microscopy (SEM). Pore size and shape as well as density were determined. In vitro experiments were performed in order to evaluate the dissolution behavior of cisplatin in the system. X-ray diffraction analysis showed that the final product consisted of a single phase, indicating that the sintering process had not affected the structure of the HA. Energy dispersive X-ray analysis (EDX) showed absence of impurities. Pore diameters were in the range 15--34 microm. SEM showed that the material presented a highly interconnected spheroidal porous network with open micropores and closed macropores. In vitro experiments showed significant differences in the release rate of cisplatin between three different porosities.
BMC Dermatology | 2001
Maria Bernadete Riemma Pierre; Antonio C. Tedesco; Juliana Maldonado Marchetti; M. Vitória L. B. Bentley
BackgroundPhotodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) is a skin cancer therapy that still has limitations due to the low penetration of this drug into the skin. We have proposed in this work a delivery system for 5-ALA based on liposomes having lipid composition similar to the mammalian stratum corneum (SCLLs) in order to optimize its skin delivery in Photodynamic Therapy (PDT) of skin cancers.MethodsSCLLs were obtained by reverse phase evaporation technique and size distribution of the vesicles was determinated by photon correlation spectroscopy. In vitro permeation profile was characterized using hairless mouse skin mounted in modified Franz diffusion cell.ResultsSize exclusion chromatography on gel filtration confirmed vesicle formation. SCLLs obtained by presented a degree of encapsulation of 5-ALA around 5.7%. A distribution of vesicle size centering at around 500 nm and 400 nm respectively for SCLLs and SCLLs containing 5-ALA was found. In vitro 5-ALA permeation study showed that SCLLs preparations presented higher skin retention significantly (p < 0.05) on the epidermis without SC + dermis, with a decreasing of skin permeation compared to aqueous solution.ConclusionsThe in vitro delivery performance provided by SCLLs lead to consider this systems adequate for the 5-ALA-PDT of skin cancer, since SCLLs have delivered 5-ALA to the target skin layers (viable epidermis + dermis) to be treated by topical PDT of skin cancer.
International Journal of Pharmaceutics | 1999
M. Vitória L. B. Bentley; Juliana Maldonado Marchetti; Nágila M.P.S. Ricardo; Ziad Ali-Abi; J. H. Collett
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.
Journal of Microencapsulation | 2006
Eduardo Ricci-Júnior; Juliana Maldonado Marchetti
Nanoparticles containing Zinc (II) Phthalocyanine (ZnPc) were prepared by a spontaneous emulsification diffusion method utilizing poly-(D,L lactic-co-glycolic acid) (PLGA), characterized and available in cellular culture. The process yield and encapsulation efficiency were 60% and 80%, respectively. The nanoparticles have a mean diameter of 200 nm, a narrow size distribution with polydispersive index of 0.15, smooth surface and spherical shape. ZnPc loaded nanoparticles maintain their photophysical behaviour after the encapsulation process. Photosensitizer released from nanoparticles was sustained with a burst effect of 10% for 3 days. The photocytotoxicity was evaluated on P388-D1 cells. They were incubated with ZnPc loaded Np by 6 h and exposed to 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 60% of cellular death. All the physical-chemical and photobiological measurements performed allowed one conclude that ZnPc loaded PLGA nanoparticles are a promising drug delivery system for PDT.
Drug Delivery | 2005
Anderson J. Gomes; Laurelúcia O. Lunardi; Juliana Maldonado Marchetti; Claure N. Lunardi; Antonio C. Tedesco
The interaction of polymeric nanoparticles formulated from the biodegradable polymer poly(DL-lactide-co-glycolide) loaded with bacteriochlorophyll-a was studied in homogeneous solution and in vitro in the presence of a macrophage cell line (P388-D1-ATCC). Photodynamic therapy (PDT) activity after different laser doses also was investigated. Scanning electron microscopy analysis of cell phagocyte nanoparticles showed that after 30 min of incubation most of the nanoparticles are in a clear adhesion process to the cell surface. The majority of nanoparticles became phagocytic after 2 hr of incubation time. After laser irradiation of the dye-containing system a total photodamage by nanoparticle phagocyte cells was observed and the cell survival was quantified by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide test. Our results indicate that polymeric nanoparticles work as an efficient drug delivery system for PDT drugs. This approach can be widely used for many other hydrophobic photosensitizers with higher aggregation tendency in neoplastic cell treatment.
Journal of drug delivery | 2011
Juliana Saraiva; Samantha Sant'Anna Marotta-Oliveira; Simone Aparecida Cicillini; Josimar O. Eloy; Juliana Maldonado Marchetti
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 systemic in vivo delivery and dose control are needed. One strategy for addressing these limitations and thus increasing the utility of NO donors is based on nanotechnology.
Colloids and Surfaces B: Biointerfaces | 2016
Josimar O. Eloy; Raquel Petrilli; José Fernando Topan; Heriton Marcelo Ribeiro Antonio; Juliana Palma Abriata Barcellos; Deise L. Chesca; Luciano Neder Serafini; Daniel Guimarães Tiezzi; Robert J. Lee; Juliana Maldonado Marchetti
Paclitaxel and rapamycin have been reported to act synergistically to treat breast cancer. Albeit paclitaxel is available for breast cancer treatment, the most commonly used formulation in the clinic presents side effects, limiting its use. Furthermore, both drugs present pharmacokinetics drawbacks limiting their in vivo efficacy and clinic combination. As an alternative, drug delivery systems, particularly liposomes, emerge as an option for drug combination, able to simultaneously deliver co-loaded drugs with improved therapeutic index. Therefore, the purpose of this study is to develop and characterize a co-loaded paclitaxel and rapamycin liposome and evaluate it for breast cancer efficacy both in vitro and in vivo. Results showed that a SPC/Chol/DSPE-PEG (2000) liposome was able to co-encapsulate paclitaxel and rapamycin with suitable encapsulation efficiency values, nanometric particle size, low polydispersity and neutral zeta potential. Taken together, FTIR and thermal analysis evidenced drug conversion to the more bioavailable molecular and amorphous forms, respectively, for paclitaxel and rapamycin. The pegylated liposome exhibited excellent colloidal stability and was able to retain drugs encapsulated, which were released in a slow and sustained fashion. Liposomes were more cytotoxic to 4T1 breast cancer cell line than the free drugs and drugs acted synergistically, particularly when co-loaded. Finally, in vivo therapeutic evaluation carried out in 4T1-tumor-bearing mice confirmed the in vitro results. The co-loaded paclitaxel/rapamycin pegylated liposome better controlled tumor growth compared to the solution. Therefore, we expect that the formulation developed herein might be a contribution for future studies focusing on the clinical combination of paclitaxel and rapamycin.