Pharmaceutical Science, Drug Discovery, Cancer Research
64
Scopus Publications
Scopus Publications
Direct Retrieval of Biomechanical and Hydrodynamic Parameters for Drug Carrier Liposomes Using Conventional Extrusion Processes Maria Victoria Heiderick Machado, Maria Luiza Barbosa Pertence, Caroline Mari Ramos Oda, Jaqueline Aparecida Duarte, Ubirajara Agero, Elaine Amaral Leite, Angelo Malachias ACS Omega, 2026 Physical parameters such as membrane elasticity and solution viscosity in a liquid medium play crucial roles in the effectiveness of drug delivery. Liposome formulations, used in both research and clinical contexts, are usually designed to achieve desired chemical stability, particle size, and drug encapsulation efficiency. However, meeting such requirements may not suffice in order to succeed in in vivo tests, which can be frustrated due to poor evaluation of biomechanical conditions. In this work, we introduce simple biomechanical evaluation protocols that make use of conventional pressure-based liposome extrusion as well as dynamic light scattering results to extract elastic (mechanical) and hydrodynamic (viscosity) properties of colloidal solutions of liposomes. We describe a sequence of analytical steps that need to be carried out in order to obtain macroscopic results that are directly comparable to those of other methods. Two distinct and complementary procedures are presented: the first uses a systematic variation of extrusion pressure, giving access to the viscosity of the solution, and the second being a statistical evaluation of the particle size distribution obtained by dynamic light scattering, providing elasticity constants for liposomal systems. Both methods carry the advantage of generating results for the liposome suspension that will be applied to real systems, thereby offering a more realistic and integrative characterization compared with microscopic techniques that usually present incomplete statistical coverage.
Co-administration of paclitaxel and cisplatin liposomal improves efficacy and reduces toxicity of chemotherapy agents in murine breast cancer model Heloisa Athaydes Seabra Ferreira, Amanda Louize Rickli Séllos Zorszin, Isabela Torres Gouvêa, Caroline Mari Ramos Oda, Jaqueline Aparecida Duarte, Juliana de Oliveira Silva, Izabella Thaís Silva, André Luis Branco de Barros, Elaine Amaral Leite Brazilian Journal of Pharmaceutical Sciences, 2026 Paclitaxel (PTX) and cisplatin (CDDP) are potent cytotoxic drugs that target distinct intracellular pathways employed together for breast cancer therapy. While studies indicate enhanced treatment efficacy with drug combinations, the concomitant rise in adverse effects remains a concern. This study assessed the potential of co-administration of these drugs encapsulated into pH-sensitive liposomes (SpHL) against a murine triple-negative breast cancer model. The cytotoxicity studies revealed a concentration-dependent relationship between drug concentration and cell viability for both drugs. The combination effect of free drugs at IC50 and IC50x2 showed an additive effect, while co-treatment with SpHL-PTX:SpHL-CDDP at IC50x4 (1:3 molar ratio) displayed strong synergism (CI = 0.52). Other combinations exhibited antagonism (CI > 2.0). In vivo studies were performed at PTX:CDDP 1:3 molar ratio in two regimen protocols: single or dual dose protocol, resulting in different cumulative doses. Tumor growth was significantly decreased when two doses of free or encapsulated drugs were used compared to single-dose administration. Notably, encapsulated dual-dose treatments demonstrated enhanced antitumor efficacy, diminished systemic toxicity, and zero mortality. In conclusion, our study underscores the promising potential of co-administering encapsulated drugs into SpHL, highlighting their superior efficacy and reduced toxicity in breast cancer treatment compared to free drugs.
Metformin-Loaded Fusogenic Liposome Improves the Therapeutic Efficacy and Safety of Doxorubicin in a Breast Cancer Treatment Thaís Mendes Pinheiro, Thaís Cristina de Amaral Almeida, Juliana de Oliveira Silva, Júlia Lobato Lopes, Geovanni Dantas Cassali, Marilia Martins Melo, Marthin Raboch Lempek, Raquel da Silva Ferreira, Danyelle M. Townsend, Elaine Amaral Leite, André Luis Branco de Barros ACS Omega, 2025 High Resolution Image Download MS PowerPoint Slide Breast cancer is a tumor with high incidence and mortality rates worldwide. Chemotherapeutic treatment consists of the systemic use of anticancer agents such as Doxorubicin (DOX). Recently, Metformin (MET), an antidiabetic drug, has been studied as an adjuvant in cancer treatment due to its action on proteins that regulate cell proliferation. DOX and MET have distinct drug distribution and pharmacokinetic parameters. Thus, strategies to equalize the delivery of these drugs to tumor tissue have been developed. In this context, liposomes are a promising alternative for increasing the effectiveness of cancer treatment with DOX and MET. This study aimed to prepare, characterize, and evaluate the antitumor activity of fusogenic liposomes containing DOX or MET. The liposomes were prepared by the Bangham method and characterized physicochemically. The prepared nanosystems (Lip-MET and Lip-DOX) showed diameters of approximately 120 nm, polydispersity index lower than 0.3, zeta potential close to neutrality, and drug encapsulation content of 98.8% ± 18.7 for Lip-DOX and 10.1% ± 0.5 for Lip-MET. To evaluate the antitumor activity, 4T1 breast tumor-bearing mice were used as a model. Once the tumor reached ∼100 mm 3, mice received four administrations (on days 1, 3, 5, and 7), each containing 5 mg/kg of DOX and 15 mg/kg of MET. A significant decrease in tumor volume was observed in animals treated with Lip-DOX + Lip-MET, compared to the other groups, evidenced by a tumor growth inhibition rate of 87.2%. It is also noteworthy that the Lip-DOX + Lip-MET treatment resulted in a significant decrease in lung and liver metastases. In these animals, 1–3 foci of lung metastases were observed, compared to control animals that reached 7–10 foci. In addition, 100% of the animals treated with free DOX presented arrhythmias, while only 40% of the animals treated with Lip-DOX + Lip-MET presented these cardiac alterations. Therefore, the coadministration of liposomes loading DOX and MET showed promise for increasing antitumor activity and safety in breast cancer treatment.
Intranasal delivery of insulin: An update on status quo and challenges for diabetes treatment Chun Yuen Jerry Wong, Alberto Baldelli, Ole Tietz, Elaine Leite, Hui Xin Ong, Daniela Traini International Journal of Biological Macromolecules, 2025 Diabetes mellitus is a chronic metabolic disorder characterised by either autoimmune-mediated destruction of pancreatic β-cells or impaired physiological responses to circulating insulin. Conventional subcutaneous insulin administration does not achieve optimal pharmacokinetics due to delayed systemic absorption and its inability to replicate the prandial, pulsatile secretion pattern of endogenous insulin. In contrast, intranasal insulin delivery offers a promising non-invasive alternative, with a pharmacokinetic profile that more closely mirrors physiological insulin release following meals, thereby improving postprandial glycaemic control. This review outlines the advantages and limitations of the intranasal route for insulin administration in comparison to other delivery methods. It also describes the structural and physiological barriers of the nasal cavity, and the specific challenges associated with delivering protein therapeutics via this route. Emphasis is placed on strategies designed to enhance the mucosal permeation of insulin, including the use of nanotechnology, safe absorption enhancers and mucoadhesive polymers, drug complexation, and the development of particulate and responsive drug delivery systems. Finally, recent advances in clinical and preclinical studies of intranasal insulin formulations are discussed, highlighting the translational potential of this approach in diabetes management.
Evaluation of the Antitumor Effectiveness and Toxicity of pH-Sensitive Liposomes Coencapsulating Doxorubicin and Simvastatin in a Murine Breast Cancer Model Jaqueline A. Duarte, Eliza R. Gomes, Geovanni D. Cassali, Pierre Sicard, Sylvain Richard, Philippe Legrand, Andre L.B. de Barros, Elaine A. Leite ACS Omega, 2025 Combination therapy offers a promising strategy for treating cancer. Research shows that using drug combinations can improve effectiveness against tumors. However, the potential enhancement of adverse effects remains a major concern. The association of statins with anticancer agents has been shown to improve anticancer therapy outcomes and reduce toxicity. This study investigated a pH-sensitive liposomal formulation coencapsulating doxorubicin (DOX) and simvastatin (SIM), referred to as SpHL-D-S, at various molar ratios (DOX:SIM, 1:1, 1:2, and 2:1) for its potential in treating breast tumors. The drug combination at a 1:1 ratio had more significant cytotoxicity than DOX alone on 4T1 breast cancer cell inhibition, with lower IC50 values, and demonstrated a synergistic effect across all concentrations tested. In vivo cardiotoxicity study revealed that 1:1 SpHL-D-S attenuated the short-term cardiotoxic effects of DOX. The antitumor efficacy of the 1:1 ratio, using either the free or encapsulated form, was evaluated in BALB/c mice with 4T1 breast tumors. No significant difference in tumor volume was observed between the SpHL-D-S and DOX:SIM groups after 8 days of treatment. However, the use of SpHL-D-S demonstrated a significant advantage, notably reducing toxicity. Additionally, SpHL-D-S treatment provided important protection for SIM against cardiac and hepatic disorders. In all mice, free DOX promoted cell vacuolization in the heart, which was reduced in animals receiving SpHL-D-S. These findings suggest that the coencapsulation of DOX and SIM in pH-sensitive liposomes may enhance the safety of breast cancer treatment.
Antifungal Efficacy of a Thiazolyl Hydrazone Derivative Incorporated into a Self-Emulsifying Drug Delivery System in a Murine Model of Cryptococcosis Iara R. Silva, Victor A. T. Leocádio, Gustavo J. C. Freitas, Renata B. Oliveira, Elaine A. Leite, Daniel A. Santos, Isabela C. César ACS Omega, 2025 2-[2-(Cyclohexylmethylene)hydrazinyl]-4-phenylthiazole (RN104) has shown notable antifungal activity against Cryptococcus species and low toxicity. This study aimed to assess the antifungal efficacy and survival benefits of RN104 incorporated into a self-emulsifying drug delivery system (SEDDS-RN104) compared to free RN104 and fluconazole (FCZ) in a murine model of Cryptococcus neoformans (H99) infection. The results demonstrated that SEDDS-RN104 significantly enhanced survival rates compared to free RN104 and FCZ, reducing the event rate (death) by 78% compared to FCZ. The mean survival time was 25 days in the SEDDS-RN104 group, compared to 14 days for free RN104 and 19 days for FCZ. Additionally, the fungal burden in the lungs was markedly reduced in the SEDDS-RN104 group, as confirmed by histopathological analysis. These findings suggest that SEDDS-RN104 effectively addresses the pharmacokinetic limitations of RN104, enhancing its antifungal efficacy and positioning it as a promising therapeutic alternative for cryptococcal infections.
Editorial: Cancer and inflammatory diseases research: from the basics to the precision medicine Adriano Sabino, Masamitsu Kanada, Elaine Leite, Mariana Quezado, Whocely Victor de Castro Frontiers in Pharmacology, 2024 Exosomes, extracellular vesicles rich in bioactive substances such as DNA, RNA, lipids, and proteins, play a crucial role in cell-to-cell communication and the pathogenesis of colorectal cancer (CRC). A comprehensive review focuses on the relatively unexplored area of exosomal genomic DNA (gDNA) and its significance in CRC. Exosome gDNA, which includes clinically relevant tumorspecific mutation genes, is pivotal in liquid biopsy applications for early diagnosis and treatment. Additionally, exosome gDNA influences immune and metabolic functions in CRC, positioning it as a critical target for future research and clinical interventions. https://doi.org/10.3389/fphar.2022.923232Poly ADP-ribose polymerase inhibitors (PARPis) have been effective in treating BRCA1/2 mutation-related cancers. A case study of a 40-year-old man with metastatic cutaneous squamous cell carcinoma (cSCC) with a BRCA2 mutation demonstrated the efficacy of PARPi fluzoparib. This treatment resulted in tumor stability and progression-free survival of five months, suggesting that PARPis can be a viable option for cSCC patients with BRCA mutations, thereby expanding the therapeutic options for this patient population. https://doi.org/10.3389/fphar.2022.968060An extensive study on breast cancer patients highlights the importance of understanding mortality from various causes to improve healthcare planning and clinical predictions. The research, involving 12,742 women, revealed that breast cancer is the leading cause of death, followed by cardiovascular disease. Notably, the contribution of breast cancer to overall mortality varied significantly by age and disease stage, emphasizing the need for age-specific and stagespecific survivorship care models that incorporate multidisciplinary approaches. https://doi.org/10.3389/fonc.2023.1270877Innovative approaches in drug delivery, such as foam-based intraperitoneal chemotherapy (FBIC), are being explored to improve treatment efficacy and safety. A study on swine models demonstrated the feasibility and safety of using doxorubicin in FBIC. The results showed promising intraoperative and postoperative outcomes without significant complications, suggesting that FBIC could be a viable alternative to traditional liquid solutions for intraperitoneal chemotherapy, pending further long-term studies. https://doi.org/10.3389/fphar.2023.1276759Cellular immunotherapy, particularly CAR T cell therapy, has revolutionized cancer treatment. However, monitoring these therapies remains challenging. Researchers have developed a synthetic Notch (synNotch) receptor system that links immune-cancer cell interactions to a simple blood test. This system allows for the detection of intratumoral activity via a secreted reporter, providing a convenient and effective method to monitor the efficacy of immunotherapies and potentially improving patient-specific treatment strategies. https://doi.org/10.3389/fphar.2023.1304194 6. Janus Kinase Inhibitors: From Autoimmune Diseases to Cancer Therapy Janus kinase (JAK) inhibitors, initially developed for autoimmune diseases, have shown promise in cancer therapy due to their role in cytokine signaling pathways involved in tumorigenesis. A systematic review of JAK inhibitors highlighted their anti-tumor potential and clinical applicability. The review underscores the importance of further studies to optimize their use in oncology, potentially offering new therapeutic avenues for cancer patients. https://doi.org/10.3389/fphar.2023.1326281Adalimumab, a widely used biologic for inflammatory diseases, benefits from therapeutic drug monitoring (TDM) to optimize treatment outcomes. A systematic review assessed the impact of TDM on adalimumab therapy, finding that proactive TDM can guide dose adjustments and improve clinical responses. However, the evidence was not statistically significant, highlighting the need for more robust studies to validate the role of TDM in managing adalimumab therapy effectively. https://doi.org/10.3389/fphar.2024.1376708Ferroptosis, an iron-dependent form of cell death, has emerged as a potential target for cancer therapy. Recent research explores the interplay between ferroptosis and the ubiquitin-proteasome system (UPS), which regulates protein stability. The study highlights key regulators of ferroptosis, such as GPX4 and NRF2, and their modulation by the UPS. Understanding this relationship could lead to novel therapeutic strategies that harness ferroptosis to combat cancer. https://doi.org/10.3389/fphar.2024.1383203 9. Clobenpropit and the CXCL12/CXCR4 Axis Clobenpropit, a histamine H3 receptor antagonist, has shown potential in treating autoimmune diseases and cancer by inhibiting the CXCR4 receptor. The CXCL12/CXCR4 axis is crucial in various biological processes, including cell proliferation, migration, and inflammation. A review of Clobenpropit's effects on this pathway suggests that it could be an effective therapeutic agent for managing diseases like juvenile idiopathic arthritis and certain cancers, providing a new avenue for targeted therapy. https://doi.org/10.3389/fphar.2024.1410104The articles featured in this Research Topic highlight the diverse and innovative approaches being explored in cancer and inflammatory disease research. From the molecular mechanisms of exosomes and ferroptosis to the clinical applications of PARPis and JAK inhibitors, these studies underscore the importance of integrating basic research with clinical practice. As precision medicine continues to evolve, these advancements will play a crucial role in developing more effective and personalized treatments, ultimately improving patient outcomes and transforming healthcare.
Co-Encapsulation of Simvastatin and Doxorubicin into pH-Sensitive Liposomes Enhances Antitumoral Activity in Breast Cancer Cell Lines Jaqueline Aparecida Duarte, Eliza Rocha Gomes, André Luis Branco De Barros, Elaine Amaral Leite Pharmaceutics, 2023 Doxorubicin (DOX) is a potent chemotherapeutic drug used as the first line in breast cancer treatment; however, cardiotoxicity is the main drawback of the therapy. Preclinical studies evidenced that the association of simvastatin (SIM) with DOX leads to a better prognosis with reduced side effects and deaths. In this work, a novel pH-sensitive liposomal formulation capable of co-encapsulating DOX and SIM at different molar ratios was investigated for its potential in breast tumor treatment. Studies on physicochemical characterization of the liposomal formulations were carried out. The cytotoxic effects of DOX, SIM, and their combinations at different molar ratios (1:1; 1:2 and 2:1), free or co-encapsulated into pH-sensitive liposomes, were evaluated against three human breast cancer cell lines (MDA-MB-231, MCF-7, and SK-BR-3). Experimental protocols included cell viability, combination index, nuclear morphological changes, and migration capacity. The formulations showed a mean diameter of less than 200 nm, with a polydispersity index lower than 0.3. The encapsulation content was ~100% and ~70% for DOX and SIM, respectively. A more pronounced inhibitory effect on breast cancer cell lines was observed at a DOX:SIM molar ratio of 2:1 in both free and encapsulated drugs. Furthermore, the 2:1 ratio showed synergistic combination rates for all concentrations of cell inhibition analyzed (50, 75, and 90%). The results demonstrated the promising potential of the co-encapsulated liposome for breast tumor treatment.
Mechanistic insights into the intracellular release of doxorubicin from pH-sensitive liposomes Samara Bonesso dos Reis, Juliana de Oliveira Silva, Fernanda Garcia-Fossa, Elaine Amaral Leite, Angelo Malachias, Gwenaelle Pound-Lana, Vanessa Carla Furtado Mosqueira, Mônica Cristina Oliveira, André Luís Branco de Barros, Marcelo Bispo de Jesus Biomedicine and Pharmacotherapy, 2021
Influence of PEG coating on the biodistribution and tumor accumulation of pH-sensitive liposomes Shirleide Santos Nunes, Renata Salgado Fernandes, Carolina Henriques Cavalcante, Isabela da Costa César, Elaine Amaral Leite, Sávia Caldeira Araújo Lopes, Alice Ferretti, Domenico Rubello, Danyelle M. Townsend, Mônica Cristina de Oliveira, Valbert Nascimento Cardoso, André Luís Branco de Barros Drug Delivery and Translational Research, 2019
Toxicological study of a new doxorubicin-loaded pH-sensitive liposome: A preclinical approach Juliana de Oliveira Silva, Sued Eustáquio Mendes Miranda, Elaine Amaral Leite, Adriano de Paula Sabino, Karina Braga Gomes Borges, Valbert Nascimento Cardoso, Geovanni Dantas Cassali, Andrea Grabe Guimarães, Mônica Cristina Oliveira, André Luis Branco de Barros Toxicology and Applied Pharmacology, 2018
Synthesis, characterization and radiolabeling of polymeric nano-micelles as a platform for tumor delivering Caroline Mari Ramos Oda, Renata Salgado Fernandes, Sávia Caldeira de Araújo Lopes, Mônica Cristina de Oliveira, Valbert Nascimento Cardoso, Daniel Moreira Santos, Adriano Monteiro de Castro Pimenta, Angelo Malachias, Rogério Paniago, Danyelle M. Townsend, Patrick M. Colletti, Domenico Rubello, Ricardo José Alves, André Luís Branco de Barros, Elaine Amaral Leite Biomedicine and Pharmacotherapy, 2017
Antitumor effectiveness and toxicity of cisplatin-loaded long-circulating and pH-sensitive liposomes against Ehrlich ascitic tumor Laís de Carvalho Maroni, Amanda Cardoso de Oliveira Silveira, Elaine Amaral Leite, Marília Martins Melo, Ana Flávia de Carvalho Ribeiro, Geovani Dantas Cassali, Cristina Maria de Souza, Elaine Maria Souza-Fagundes, Iramaya Rodrigues Caldas, Márcio Sobreira Silva Araújo, Olindo Assis Martins-Filho, Mônica Cristina de Oliveira, Andréa Teixeira-Carvalho Experimental Biology and Medicine, 2012