Mônica Cristina de Oliveira's research while affiliated with Federal University of Minas Gerais and other places

Publications (122)

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PEGylated liposomes are largely studied as long-circulating drug delivery systems. Nevertheless, the addition of PEG can result in reduced interactions between liposomes and cells, hindering liposomal internalization into target cells. The presence of PEG on the surface of pH-sensitive liposomes is not advantageous in terms of biodistribution and t...
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Combination therapy between paclitaxel (PTX) and doxorubicin (DXR) is applied as the first-line treatment of breast cancer. Co-administration of drugs at synergistic ratio for treatment is facilitated with the use of nanocarriers, such as liposomes. However, despite the high response rate of solid tumors to this combination, a synergism of cardioto...
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Objectives To circumvent cisplatin (CDDP) toxic effects and improve the antitumoural effect, our research group developed long-circulating and pH-sensitive liposomes containing CDDP (SpHL-CDDP). This study aimed to evaluate whether SpHL-CDDP is associated with intestinal protection under in-vitro conditions in the presence of host–microbiota, compa...
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Irinotecan (IRN) is a semisynthetic derivative of camptothecin that acts as a topoisomerase I inhibitor. IRN is used worldwide for the treatment of several types of cancer, including colorectal cancer, however its use can lead to serious adverse effects, as diarrhea and myelosuppression. Liposomes are widely used as drug delivery systems that can i...
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The main goal of this study is to evaluate the efficacy of the paclitaxel (PTX) drug formulated with a liposomal nanosystem (L-PTX) in a peritoneal carcinomatosis derived from ovarian cancer. In vitro cell viability studies with the human ovarian cancer line A2780 showed a 50% decrease in the inhibitory concentration for L-PTX compared to free PTX....
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Since more than 40 years liposomes have being extensively studied for their potential as carriers of anticancer drugs. The basic principle behind their use for cancer treatment consists on the idea that they can take advantage of the leaky vasculature and poor lymphatic drainage present at the tumor tissue, passively accumulating in this region. Ai...
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Over the last decade, studies showed evidence of enhanced sensitivity of triple negative breast cancer (TNBC) to DNA-damaging agents, such as cisplatin (CIS), compared to other breast cancer subtypes. Despite its high efficacy, CIS has its use limited by dose-dependent side effects, mainly nephrotoxicity and neurotoxicity. In previous studies, it h...
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pH-sensitive liposomes are interesting carriers for drug-delivery, undertaking rapid bilayer destabilization in response to pH changes, allied to tumor accumulation, a desirable behavior in the treatment of cancer cells. Previously, we have shown that pH-sensitive liposomes accumulate in tumor tissues of mice, in which an acidic environment acceler...
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The treatment against visceral leishmaniasis (VL) presents problems, mainly related to the toxicity and/or high cost of the drugs. In this context, a prophylactic vaccination is urgently required. In the present study, a Leishmania protein called LiHyE, which was suggested recently as an antigenic marker for canine and human VL, was evaluated regar...
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The control measures against visceral leishmaniasis (VL) include a precise diagnosis of disease, the treatment of human cases, and reservoir and vector controls. However, these are insufficient to avoid the spread of the disease in specific countries worldwide. As a consequence, prophylactic vaccination could be interesting, although no effective c...
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In recent years, cardiac glycosides (CGs) have been investigated as potential antiviral and anticancer drugs. Digitoxigenin (DIG) and other CGs have been shown to bind and inhibit Na⁺/K⁺-adenosinetriphosphatase (ATPase). Tumor cells show a higher expression rate of the Na⁺/K⁺-ATPase protein or a stronger affinity towards the binding of CGs and are...
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Simple size observations of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-mPEG2000) polymeric micelles (PM) with different compositions including or not paclitaxel (PTX) are unable to evidence changes on the nanocarrier structure. In such system a detailed characterization using highly sensitive techniqu...
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Breast cancer is the most incident and mortal cancer type in women, with an estimated 2 million new cases expected by 2020 worldwide, with 600,000 deaths. As not all breast cancer types respond to the anti-hormonal therapy, the development of new antineoplastic drugs is necessary. Lawsone (2-hydroxy-1,4-naphtoquinone) is a natural bioactive naphtoq...
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Background The co-encapsulation of paclitaxel (PTX) and doxorubicin (DXR) in liposomes has the potential to offer pharmacokinetic and pharmacodynamic advantages, providing delivery of both drugs to the tumor at the ratio required for synergism. Objective To prepare and characterize long-circulating and fusogenic liposomes co-encapsulating PTX and...
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Long circulating pH-sensitive liposomes have been shown to effectively deliver doxorubicin (DOX) to tumors and reduce its toxic effects. Folic acid receptors are upregulated in a wide variety of solid, epithelial tumors, including breast cancer. In order to improve liposomal endocytosis and antitumor activity, folic acid has been added to nanoparti...
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Background: In the Americas, one of the main causative species of cutaneous leishmaniasis is Leishmania (Leishmania) amazonensis. The systemic antimonials remain the most largely used option for disease control. However, this drug has significant toxicity. The development of new alternative therapies, including the identification of effective drug...
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Paclitaxel (PTX) is a microtubule-stabilizing agent widely used to treat breast cancer. Nevertheless, the low solubility of the drug and the side effects of commercial formulations available limit its clinical use. In this way, our group recently described the preparation of PTX-loaded folate-coated long circulating and pH-sensitive liposomes (SpHL...
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Background: Associating paclitaxel (PTX) to doxorubicin (DXR) is one of the main chemotherapy strategies for breast cancer (BC) management. Protocols currently available consist in administering both drugs on their maximum tolerated dose, not taking into account the possible differences in efficacy due to their combination ratio. In the present st...
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To associate paclitaxel (PTX) with doxorubicin (DXR) is one of the main chemotherapy strategies for breast cancer (BC) management. Despite the high response rates for this combination, it presents a cardiotoxic synergism, attributed to pharmacokinetic interactions between PTX and both DXR and its metabolite, doxorubicinol. One of the main strategie...
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Cancer is an important public health problem, being one of the leading causes of death worldwide. Most antineoplastic agents cause severe toxic effects and some types of cancer do not respond or are resistant to the existing pharmacotherapy, necessitating the research and development of new therapeutic strategies. Cardenolides have shown significan...
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Liposomes are lipid vesicles widely used as nanocarriers in targeted drug delivery systems for therapeutic and/or diagnostic purposes. A strategy to prolong the blood circulation time of the liposomes includes the addition of a hydrophilic polymer polyethylene glycol (PEG) moiety onto the surface of the vesicle. Several studies claim that liposome...
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Doxorubicin (DOX) is widely used in cancer treatment, however, the use of this drug is often limited due to its cardiotoxic side effects. In order to avoid these adverse effects, the encapsulation of DOX into nanosystems has been used in the last decades. In this context, pH-sensitive liposomes have been shown promising for delivering cytotoxic age...
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Polymeric micelles (PM) are versatile nanoparticles with suitable properties to tumor delivery of hydrophobic drugs such as paclitaxel (PTX) and imaging probes such as technetium-99 m. However, instability of drug content in aqueous medium and obstacles related to lengthy radiolabeling procedures, high radiation exposure and risk of human error lim...
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The era of chemotherapy began in the 1940s, but it was in the 1960s that it was seen as really promising, when the first patients with childhood acute lymphoblastic leukemia were cured with combination chemotherapy. Today, it is known that due to resistance to single agents, combination therapy is essential for tumor eradication and cure. In the la...
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A long-circulating and pH-sensitive liposome containing PTX (SpHL-PTX) was recently developed by our group. Once at an acidic environment, e.g. tumor, these liposomes undergo destabilization releasing the encapsulated drug. In this way, the aim of this study was evaluate the molecular and supramolecular interactions between the lipid bilayer and PT...
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trans-Aconitic acid (TAA) is the main constituent of the leaves from the medicinal plant Echinodorus grandiflorus, used to treat different inflammatory diseases. TAA induces a potent but short-lasting biological response, credited to its high polarity and unfavorable pharmacokinetics. Here we developed, characterized and evaluated the anti-inflamma...
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Background: PnPP-19 is a 19-amino-acid synthetic peptide previously described as a novel drug for the treatment of erectile dysfunction. Objective: The aim of this work was to evaluate the physicochemical properties of cationic transfersomes containing PnPP-19 and the skin permeation of free PnPP-19 and PnPP-19-loaded transfersomes. Method: Th...
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Breast cancer is the most common and lethal cancer type in women worldwide. Therapeutic strategies with better selectivity, such as active targeting by nanocarriers, are highly desirable. In this mini review, we briefly outline the evolution of nanocarriers culminating in actively targeted systems, the challenges faced when designing such carriers...
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Qa-2 is believed to mediate a protective immune response against cancer; however, little is known about the role of Qa-2 in tumorigenesis. Here, we used 4T1 breast cancer cells to study the involvement of Qa-2 in tumor progression in a syngeneic host. Qa-2 expression was reduced during in vivo tumor growth and in cell lines derived from 4T1-induced...
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The N-(butanoyloxyethyl)-4-(chloromethyl)-3-nitrobenzamide (BNB) is a nitroaromatic derivative with significant antitumor activity. Preformulation, forced degradation (distilled water, acid and base hydrolysis, oxidation, and light), and formulation studies were performed to investigate the chemical behavior of the molecule, the physicochemical pro...
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A range of antitumor agents for cancer treatment is available; however, they show low specificity, which often limit their use. Recently, we have reported the preparation of folate-coated long-circulating and pH-sensitive liposomes (SpHL-folate-PTX) loaded with paclitaxel (PTX), an effective drug for the treatment of solid tumors, including breast...
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The observation that different drug ratios of the same drug combination can lead to synergistic or antagonistic effects when tested against the same cancer cell line in vitro gave rise to a new trend, the ratiometric delivery. This strategy consists of co-encapsulating a specific synergistic ratio of a drug combination into a nanocarrier so that sy...
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Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors, with a high mortality rate due to the elevated risk of resistance. Natural cucurbitacins and their derivatives are recognized as promising antitumor compounds for several types of cancer, including NSCLC. In a recent study published by our research group, DACE (2-deoxy-2...
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Recent studies demonstrate that cardiac glycosides, known to inhibit Na(+)/K(+)-ATPase in humans, have increased susceptibility to cancer cells that can be used in tumor therapy. One of the most promising candidates identified so far is glucoevatromonoside, which can be isolated from the endangered species Digitalis mariana ssp. heywoodii. Due to i...
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The use of nanoparticles for diagnostic approaches leads to higher accumulation in the targeting tissue promoting a better signal-to-noise ratio and consequently, early tumor detection through scintigraphic techniques. Such approaches have inherent advantages, including the possibility of association with a variety of gamma-emitting radionuclides a...
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Cisplatin (CDDP) is a chemotherapeutic agent widely used in several anticancer protocols for instance head and neck, testicle, ovarian, lung and peritoneal carcinomatosis. According to the literature, the use of CDDP is associated with several side effects; among them, we highlighted the mucositis. CDDP, when administered by IP, promoted significan...
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Chemotherapy for bone tumors is a major challenge because of the inability of therapeutics to penetrate dense bone mineral. We hypothesize that a nanostructured formulation with high affinity for bone could deliver drug to the tumor while minimizing off-target toxicity. Here, we evaluated the efficacy and toxicity of a novel bone-targeted, pH-sensi...
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The high incidence and mortality of breast cancer supports efforts to develop innovative imaging probes to effectively diagnose, evaluate the extent of the tumor, and predict the efficacy of tumor treatments while concurrently and selectively delivering anticancer agents to the cancer tissue. In the present study we described the preparation of tec...
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This study aimed to evaluate cell injuries in Bifidobacterium longum 51A caused by different microencapsulation processes. For this purpose, the probiotic was microencapsulated by emulsification using alginate with starch or chitosan as well as by spray drying using skim milk as the matrix. The microcapsules were characterized by atomic force micro...
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Nowadays cancer is one of the most common causes of deaths worldwide. Conventional antitumor agents still present various problems related to specificity for tumor cells often leading to therapeutic failure. Nanoscale particles are considered potential alternative to direct access of drugs into tumor cells, therefore increasing the drug accumulatio...
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Background: Despite recent advances in cancer therapy, the treatment of bone tumors remains a major challenge. A possible underlying hypothesis, limitation, and unmet need may be the inability of therapeutics to penetrate into dense bone mineral, which can lead to poor efficacy and high toxicity, due to drug uptake in healthy organs. The developme...
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Purpose: Therapeutic agents used in chemotherapy have low specificity leading to undesired severe side effects. Hence, the development of drug delivery systems that improve drug specificity, such as liposome moieties, is an alternative to overcome chemotherapy limitations and increase antitumor efficacy. In this study, the biodistribution profile...
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Background Ursolic acid (UA) is a triterpene found in different plant species, possessing antitumor activity, which may be a result of its antiangiogenic effect. However, UA has low water solubility, which limits its use because the bioavailability is impaired. To overcome this inconvenience, we developed long-circulating and pH-sensitive liposomes...
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Purpose: Pancreatic cancer is the fourth most common cause of cancer-related death in the USA. This is mainly because of the chemoresistance of this type of tumor; thus, the development of novel therapeutic modalities is needed. Methods: Long-circulating and pH-sensitive liposomes containing cisplatin (SpHL-CDDP) were administered systemically i...
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Aim: More sensitive and accurate imaging approaches for early detection and therapy monitoring of lung tumours are needed to ameliorate prognosis and outcome. Lung tumours are known to overexpress receptors for bombesin-like peptides. However, thus far, no study has demonstrated the potential role of bombesin-like peptides in identifying A549 lung...
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Objective: Early diagnosis of malignant tumors is essential to successfully plan a radical and curative approach. In this study we describe the direct radiolabeling of doxorubicin (DOX) at physiological pH to identify murine breast tumor (4T1 cells)-bearing BALB/c mice. Materials and methods: Technetium-99m (Tc) DOX was prepared by adding Tc-per...
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Paclitaxel (PTX) is widely used as a first-line treatment for patients with metastatic breast cancer; however, its poor water solubility represents a major challenge for parenteral administration. The encapsulation of the PTX in drug-delivery systems with high affinity for tumor sites could improve the uptake and increase its therapeutic efficacy....
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Theranostic nanosystems have attracted the attention of many scientists in worldwide due to its ability to accumulate and release selectively, in specific sites, compounds capable to generate images and to treat tumors, allowing simultaneously, the diagnose and treatment of cancer. Radioactive Gadolinium-159, a beta e gamma radiation emitter, has t...
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The aim of this study was to evaluate the ability of phytate radiolabeled with technetium-99m (Tc-phytate) to identify inflammatory processes. Radiolabeling efficiency analyses were carried out by thin-layer chromatography on silica gel strips, yielding a radiochemical purity of 92%. In addition, the partition coefficient of Tc-phytate, obtained in...
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A simple and sensitive method using first-derivative ultraviolet spectrophotometry (DS?UV) was developed, validated, and compared to the high performance liquid chromatography (HPLC) method for quantification of paclitaxel (PTX) in a liposomal formulation. Different analytical performance parameters such as linearity, accuracy, precision, specifici...
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Animal venoms have been widely investigated throughout the world. The great number of biotechnological articles as well as patent applications in the field of drug discovery based on these compounds indicates how important the source is. This review presents a list of the most studied Brazilian venomous animal species and shows the most recent pate...
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Mucopolysaccharidosis type I (MPS I) is an autosomal disease caused by alpha-l-iduronidase deficiency. This study proposed the use of cationic nanoemulsions as non-viral vectors for a plasmid (pIDUA) containing the gene that codes for alpha-l-iduronidase. Nanoemulsions composed of medium chain triglycerides (MCT)/1,2-dioleoyl-sn-glycero-3-phosphoet...
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Inflammatory and infectious diseases are one of the most common causes of mortality and morbidity. This paper aimed to prepare and to evaluate the ability of long-circulating and pH-sensitive liposomes, trapping a radiotracer, to identify inflamed focus. The physicochemical characterization of freeze-dried liposomes, using glucose as cryoprotectant...
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Previous work revealed that 25-day tumour focus is the optimal developmental stage to assess LNCaP prostate tumour by scintigraphic images using technetium-99m (99mTc)-2-hydrazinonicotinamide (HYNIC)-beta-alanine (βAla)-Bombesin(7-14) in a murine model. However, more studies are essential to evaluate the feasibility of this radiopeptide as a radiot...
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Osteomyelitis is a progressive destruction of bones caused by microorganisms. Inadequate or absent treatment increases the risk of bone growth inhibition, fractures, and sepsis. Among the diagnostic techniques, functional images are the most sensitive in detecting osteomyelitis in its early stages. However, these techniques do not have adequate spe...
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Bombesin (BBN) is a tetradecapeptide that binds specifically to gastrin-releasing peptide receptors in humans. These receptors are over-expressed in several forms of cancer; radiolabeled BBN could therefore be used to detect such cancers. However, the degradation of peptides is a critical issue in the development of tumor tracers. Liposomes can be...
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Ursolic acid (UA) is a triterpene found in different plant species that has been shown to possess significant antitumor activity. However, UA presents a low water solubility, which limits its biological applications. In this context, our research group has proposed the incorporation of UA in long-circulating and pH-sensitive liposomes (SpHL-UA).The...
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Twenty-seven nitrated and non-nitrated compounds has been synthesized and tested for their growth inhibitory activity on three human cancer cells lines. Fourteen compounds were able to inhibit more than 50% of the growth of at least one of the cancer cell lines and five compounds exhibited high antiproliferative activity on human cancer cell lines...
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We have previously reported on a study of structure-activity relationship in a series of 2,3,4-substituted oxazolidines recently discovered by our group varying the substituent at ring or stereochemistry of the oxazolidine ring. We discovered the cytotoxic and pro-apoptotic potential of compounds 1-2 with a good selectivity against cancer cell line...
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The lymph node carcinoma of the prostate (LNCaP) cell line is widely used in prostate cancer diagnostic studies. However, the optimal developmental stage during which to assess LNCaP prostate tumours by in vivo molecular imaging has not been established. This study aimed to assess LNCaP prostate tumours by scintigraphic imaging using technetium-99m...
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To develop a nanostructured lipid carrier (NLC) co-loaded with doxorubicin and docosahexaenoic acid (DHA) and to evaluate its potential to overcome drug resistance and to increase antitumoral effect in MCF-7/Adr cancer cell line. The NLC was prepared by a hot homogenization method and characterized for size, zeta potential, entrapment efficiency (E...
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Nitroheterocyclic compounds have received considerable interest as hypoxia-selective cytotoxins (HSC) for cancer treatment. In the present study, we investigated antitumor activity of an iodide analogue of metronidazole, 1-(2-iodoethyl)-2-methyl-5-nitroimidazole (MTZ-I), using Swiss mice bearing solid Ehrlich tumor. MTZ-I showed potent anti-cancer...