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Dive into the research topics where Mônica Cristina de Oliveira is active.

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Featured researches published by Mônica Cristina de Oliveira.


European Journal of Pharmaceutical Sciences | 2013

New approach to improve encapsulation and antitumor activity of doxorubicin loaded in solid lipid nanoparticles

Samuel Vidal Mussi; Renata Carvalho Silva; Mônica Cristina de Oliveira; Carolina Madeira Lucci; Ricardo Bentes Azevedo; Lucas Antônio Miranda Ferreira

This work aimed to develop solid lipid nanoparticles (SLNs) loaded with doxorubicin evaluating the influence of docosahexaenoic acid (DHA), a polyunsaturated fatty acid that enhances the activity of anticancer drugs, on drug encapsulation efficiency (EE). The SLN were characterized for size, zeta potential, entrapment efficiency (EE) and drug release. Studies of in vitro antitumor activity and cellular uptake were also conducted. The reduction in particle size (from 127 ± 14 to 94 ± 1 nm) and negative charges were obtained for SLN loaded with DHA and triethanolamine (TEA), amine used to increase the solubility of doxorubicin in melted lipid. The EE was significantly improved from 36 ± 4% to 99 ± 2% for SLN without and with DHA at 0.4%, respectively. The doxorubicin release in a slightly acid medium (pH 5.0) was higher than that observed at physiological pH. The in vitro studies clearly showed the higher cytotoxicity of doxorubicin-DHA-loaded SLN than free doxorubicin+DHA on human lung tumor cell line (A549) and the improved cellular uptake achieved with the drug encapsulation can be an explanation. These findings suggest that DHA-doxorubicin-loaded SLN is a promising alternative for the treatment of cancer.


Therapeutic Delivery | 2013

pH-sensitive liposomes for drug delivery in cancer treatment

Diego dos Santos Ferreira; Sávia Caldeira de Araújo Lopes; Marina Santiago Franco; Mônica Cristina de Oliveira

In recent years, liposomes have been employed with growing success as pharmaceutical carriers for antineoplastic drugs. One specific strategy used to enhance in vivo liposome-mediated drug delivery is the improvement of intracytoplasmic delivery. In this context, pH-sensitive liposomes (pHSLip) have been designed to explore the endosomal acidification process, which may lead to a destabilization of the liposomes, followed by a release of their contents into the cell cytoplasm. This review considers the current status of pHSLip development and its applicability in cancer treatment, focusing on the mechanisms of pH sensitivity and liposomal composition of pHSLip. The final section will discuss the application of these formulations in both in vitro and in vivo studies of antitumor efficacy.


Life Sciences | 2000

Improvement of in vivo stability of phosphodiester oligonucleotide using anionic liposomes in mice.

Mônica Cristina de Oliveira; Valérie Boutet; Elias Fattal; Didier Boquet; Jean-Marc Grognet; Patrick Couvreur; Jean-Robert Deverre

Antisense phosphodiester oligonucleotides (ODN) are unstable in biological fluids due to nuclease-mediated degradation and therefore cannot be used in most antisense therapeutic applications. We describe here an in vitro and in vivo stabilization of a 15 mer phosphodiester sequence using anionic liposomes. Two formulations have been studied: DOPC/OA/CHOL and DOPE/OA/CHOL (pH-sensitive liposomes). Our in vitro findings reveal the same stabilization effect in mouse plasma for both anionic liposomes. In vivo investigation showed a great protective effect for both formulations after intravenous administration to mice. By contrast with in vitro results, a higher protection of ODN was observed with DOPC/OA/CHOL liposomes compared to the DOPE/OA/CHOL formulation. The latter was degraded in blood (75% of the injected dose at 5 min) probably due to interactions with blood components, and the remaining (25% at 5 min) was distributed mostly to the liver and spleen. DOPC liposomes were remarkably stable in blood and were distributed more slowly to all studied organs (liver, spleen, kidneys and lungs). Intact ODN was still observed in some organs (liver, spleen, lungs), but not in blood, 24 hours after DOPC liposome administration. These results suggest that this antisense strategy using carrier systems may be applicable to the treatment of diseases involving the reticuloendothelial system.


Life Sciences | 2009

Acute toxicity of long-circulating and pH-sensitive liposomes containing cisplatin in mice after intraperitoneal administration

Elaine Amaral Leite; Cristiane dos Santos Giuberti; Alberto Julius Alves Wainstein; Ana Paula D.L. Wainstein; Luiz Gonzaga Vaz Coelho; Ângela Maria Quintão Lana; Paulo Roberto Savassi-Rocha; Mônica Cristina de Oliveira

AIMS The objective of this work was to evaluate the acute toxicity of long-circulating and pH-sensitive liposomes containing cisplatin (SpHL-CDDP), after their intraperitoneal administration in male and female mice. MAIN METHODS After single administration of free CDDP (5,10,and 20 mg/kg) or SpHL-CDDP (7,12,30,45 and 80 mg/kg), the body weight was recorded and the LD(50) was calculated. Blood samples were collected for biochemical and hematological analysis. Kidneys, liver, spleen and bone marrow were removed to histopathological examination. KEY FINDINGS Mice treated with high doses of free CDDP showed a greater loss of body weight and more delayed recovery time than those treated with SpHL-CDDP. The LD(50) values for SpHL-CDDP treatment for male and female mice groups were 2.7 and 3.2 fold higher, respectively, than that obtained for free CDDP. The red and white blood cells counts and quantification of hemoglobin and hematocrit presented no change upon administration of SpHL-CDDP treatment. Free CDDP treatment, however, did lead to an appearance of mild anemia and a reduction in total white blood cell counts. As regards nephrotoxicity, it was observed that free CDDP treatment caused pronounced alterations in the blood urea and creatinine levels of mice. In contrast, these parameters were slightly altered only after SpHL-CDDP treatment at a dose of 30 mg/kg. Microscopic analysis of kidneys from mice treated with SpHL-CDDP showed no morphological alteration. Concerning hepatotoxicity, no histopathological alteration was observed after both treatments. SIGNIFICANCE These findings reveal that SpHL-CDDP can eliminate CDDP-induced toxicity and is thus a promising candidate for intraperitoneal chemotherapy.


Bioorganic & Medicinal Chemistry Letters | 2010

Bombesin derivative radiolabeled with technetium-99m as agent for tumor identification.

André Luís Branco de Barros; Luciene das Graças Mota; Carolina D. Ferreira; Mônica Cristina de Oliveira; Alfredo M. Goes; Valbert Nascimento Cardoso

A bombesin derivative was successfully radiolabeled in high labeling yield. Biodistribution studies and scintigraphic images in Ehrlich tumor-bearing mice were performed. This compound showed high accumulation in tumor tissue with high tumor-to-muscle and tumor-to-blood ratios. Thus, (99m)Tc-HYNIC-Bombesin((7-14)) could be used as an agent for tumor diagnosis.


Biophysical Chemistry | 2000

pH-Sensitive liposomes as a carrier for oligonucleotides: a physico-chemical study of the interaction between DOPE and a 15-mer oligonucleotide in excess water

Mônica Cristina de Oliveira; Véronique Rosilio; Pierre Lesieur; Claudie Bourgaux; Patrick Couvreur; Michel Ollivon; Catherine Dubernet

The cytoplasmic delivery of drugs encapsulated into pH-sensitive liposomes is under the control of a lamellar-to-hexagonal transition. In a previous study, under anhydrous conditions, oligonucleotides (ODN) encapsulated in pH-sensitive liposomes composed of dioleoylphosphatidylethanolamine (DOPE)/oleic acid (OA)/cholesterol (CHOL) were shown to modify the phase behaviour of DOPE. In the present study, the lipid/ODN interactions were evaluated in fully hydrated samples by surface tension measurements, differential scanning calorimetry, X-ray diffraction and turbidimetry. Concerning the lipids, it was shown that OA provoked a disorganisation of DOPE lamellar phases and led to the complete disappearance of hexagonal transition along with heating. The addition of CHOL further decreased the lipid packing in the bilayers. Concerning ODN, these molecules provoked an increase in the surface pressure of a DOPE/OA/CHOL monolayer, indicating the existence of molecular interactions with the lipids. At a supramolecular level, ODN induced a more ordered organisation of DOPE molecules in the lamellar and hexagonal phases, and completely abolished the disorganisational effect of OA and CHOL.


Journal of Liposome Research | 2009

Topical delivery and in vivo antileishmanial activity of paromomycin-loaded liposomes for treatment of cutaneous leishmaniasis

Guilherme Carneiro; Délia Chaves Moreira dos Santos; Mônica Cristina de Oliveira; Ana Paula Fernandes; Luciana Stransky Ferreira; Gilson Andrade Ramaldes; Elzíria de Aguiar Nunan; Lucas Antônio Miranda Ferreira

The present study aimed to evaluate the potential of liposomes loaded with paromomycin (PA), an aminoglycoside antibiotic associated with poor skin penetration, for the topical treatment of cutaneous leishmaniasis (CL). Fluid liposomes were prepared and characterized for particle size, zeta potential, and drug entrapment. Permeation studies were performed with two in vitro models: intact and stripped skin. The antileishmanial activity of free and liposomal PA was evaluated in BALB/c mice infected by Leishmania (L.) major. Drug entrapment ranged from 10 to 14%, and the type of vesicle had little influence on this parameter. Particle size and polydispersity index of the vesicles composed by phosphatidylcholine (PC) and PC/cholesterol (Chol) ranged from of 516 to 362 nm and 0.7 to 0.4, respectively. PA permeation across intact skin was low, regardless of the formulation tested, while drug penetration into skin (percent of the applied dose) from PC (7.2 ± 0.2%) and PC/Chol (4.8 ± 0.2%) liposomes was higher than solution (1.9 ± 0.1%). PA-loaded liposomes enhanced in vitro drug permeation across stripped skin and improved the in vivo antileishmanial activity in experimentally infected mice. Our findings suggest that the liposomes represent a promising alternative for the topical treatment of CL using PA.


International Journal of Nanomedicine | 2012

Encapsulation of cisplatin in long-circulating and pH-sensitive liposomes improves its antitumor effect and reduces acute toxicity

Elaine Amaral Leite; Cristina Maria de Souza; Alvaro D. Carvalho-Junior; Luiz Gv Coelho; Ângela Mq Lana; Geovanni Dantas Cassali; Mônica Cristina de Oliveira

Cisplatin (CDDP) is one of the most effective and potent anticancer drugs used as first-line chemotherapy against several solid tumors. However, the severe side effects and its tendency to provoke chemoresistance often limit CDDP therapy. To avoid these inconveniences, the present study’s research group developed long-circulating and pH-sensitive liposomes containing CDDP (SpHL-CDDP). The present study aimed to evaluate the antitumor effect and toxicity of SpHL-CDDP, as compared with that of free CDDP, and long-circulating and non- pH-sensitive liposomes containing CDDP (NSpHL-CDDP), after their intravenous administration in solid Ehrlich tumor-bearing mice. Antitumor activity was evaluated by analysis of tumor volume and growth inhibition ratio, serum vascular endothelial growth factor (VEGF) levels, and histomorphometric and immunohistochemical studies. Body weight variation and the histological examination of bone marrow and kidneys were used as toxicity indicators. A significant reduction in the tumor volume and a higher tumor growth inhibition ratio was observed after SpHL-CDDP treatment, compared with free CDDP and NSpHL-CDDP treatments. In addition, complete remission of the tumor was detected in 18.2% of the mice treated with SpHL- CDDP (16 mg/kg). As such, the administration of SpHL-CDDP, as compared with free CDDP and NSpHL-CDDP, led to a decrease in the area of necrosis and in the percentage of positive CDC 47 tumor cells. A significant reduction in the VEGF serum level was also observed after SpHL-CDDP treatment, as compared with free-CDDP treatment. SpHL-CDDP administered in a two-fold higher dose than that of free CDDP presented a loss in body weight and changes in the hematopoietic tissue morphology, which proved to be similar to that of free CDDP. No changes could be verified in the renal tissue after any formulations containing CDDP had been administered. These findings showed that SpHL-CDDP allowed for the administration of higher doses of CDDP, significantly improving its antitumor effect.


European Journal of Pharmaceutical Sciences | 2011

Liposomes radiolabeled with 159Gd: In vitro antitumoral activity, biodistribution study and scintigraphic image in Ehrlich tumor bearing mice

Daniel Crístian Ferreira Soares; Mônica Cristina de Oliveira; André Luís Branco de Barros; Valbert Nascimento Cardoso; Gilson Andrade Ramaldes

PEG-coated pH-sensitive and PEG-folate-coated pH-sensitive liposomes containing the Gd-DTPA-BMA complex were prepared and radiolabeled by neutron activation. The radiolabeled liposomes presented significant in vitro cytotoxic activity against Ehrlich tumor cells when compared with controls. The biodistribution profile of these liposomes and free (159)Gd-DTPA-BMA were studied in mice bearing a previously-developed solid Ehrlich tumor. The results demonstrated an important uptake of the formulations by the tumor tissue, with a tissue/blood partition coefficient (Kp) 3.88 and 14.16 times higher than that of the free complex for pH-sensitive PEG-coated and PEG-folate-coated liposomes containing the (159)Gd-DTPA-BMA complex, respectively. Both formulations accumulated in the liver and spleen, thereby revealing some difficulty in escaping the action of the MPS cells. The formulation without folate presented a lower renal uptake, which is desirable in patients with chronic renal failure due to the potential risk of nephrogenic systemic fibrosis (NFS). The scintigraphic study revealed that the target/non-target ratio is always greater than three for pH-sensitive PEG-coated liposome formulations and above nine for pH-sensitive PEG-folate-coated liposome formulations. The results obtained in this study demonstrated that the formulations employed can be considered to be a potential alternative for the treatment of cancer, including patients with chronic renal failure.


Bioorganic & Medicinal Chemistry Letters | 2010

A novel d-glucose derivative radiolabeled with technetium-99m: Synthesis, biodistribution studies and scintigraphic images in an experimental model of Ehrlich tumor

André Luís Branco de Barros; Valbert Nascimento Cardoso; Luciene das Graças Mota; Elaine Amaral Leite; Mônica Cristina de Oliveira; Ricardo José Alves

A d-glucose-MAG(3) derivative was successfully synthesized and radiolabeled in high labeling yield. Biodistribution studies and scintigraphic images in Ehrlich tumor-bearing mice were performed. This compound showed high accumulation in tumor tissue with high tumor-to-muscle ratio. Thus, d-glucose-MAG(3) could be considered as agent for tumor diagnosis.

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Dive into the Mônica Cristina de Oliveira's collaboration.

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Valbert Nascimento Cardoso

Universidade Federal de Minas Gerais

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Elaine Amaral Leite

Universidade Federal de Minas Gerais

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André Luís Branco de Barros

Universidade Federal de Minas Gerais

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Ricardo José Alves

Universidade Federal de Minas Gerais

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Geovanni Dantas Cassali

Universidade Federal de Minas Gerais

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Sávia Caldeira de Araújo Lopes

Universidade Federal de Minas Gerais

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Gilson Andrade Ramaldes

Universidade Federal de Minas Gerais

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Lucas Antônio Miranda Ferreira

Universidade Federal de Minas Gerais

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Liziane O.F. Monteiro

Universidade Federal de Minas Gerais

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Luciene das Graças Mota

Universidade Federal de Minas Gerais

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