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OBJECTIVE: This study aims to utilize PEGylated poly (lactic-co-glycolic acid) (PLGA) nanoparticles as a delivery system for simultaneous administration of the BRAFV600E peptide, a tumor-specific antigen, and imiquimod (IMQ). The objective is to stimulate dendritic cell (DC) maturation, activate macrophages, and facilitate antigen presentation in C57BL6 mice. METHODS: PEG-PLGA-IMQ-BRAFV600E nanoparticles were synthesized using a PLGA-PEG-PLGA tri-block copolymer, BRAFV600E, and IMQ. Characterization included size measurement and drug release profiling. Efficacy was assessed in inhibiting BPD6 melanoma cell growth and activating immature bone marrow DCs, T cells, macrophages, and splenocyte cells through MTT and ELISA assays. In vivo, therapeutic and immunogenic effects potential was evaluated, comparing it to IMQ + BRAFV600E and PLGA-IMQ-BRAFV600E nanoparticles in inhibiting subcutaneous BPD6 tumor growth. RESULTS: The results highlight the successful synthesis of PEG-PLGA-IMQ-BRAFV600E nanoparticles (203 ± 11.1 nm), releasing 73.4% and 63.2% of IMQ and BARFV600E, respectively, within the initial 48 h. In vitro, these nanoparticles demonstrated a 1.3-fold increase in potency against BPD6 cells, achieving ~ 2.8-fold enhanced cytotoxicity compared to PLGA-IMQ-BRAFV600E. Moreover, PEG-PLGA-IMQ-BRAFV600E exhibited a 1.3-fold increase in potency for enhancing IMQ cytotoxic effects and a 1.1- to ~ 2.4-fold increase in activating DCs, T cells, macrophages, and splenocyte cells compared to IMQ-BRAFV600E and PLGA-IMQ-BRAFV600E. In vivo, PEG-PLGA-IMQ-BRAFV600E displayed a 1.3- to 7.5-fold increase in potency for inhibiting subcutaneous BPD6 tumor growth compared to the other formulations. CONCLUSIONS: The findings suggest that PEG-PLGA nanoparticles effectively promote DC maturation, T cell activation, and potentially macrophage activation. The study highlights the promising role of this nanocomposite in vaccine development.
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Células Dendríticas , Imiquimode , Melanoma , Camundongos Endogâmicos C57BL , Nanopartículas , Polietilenoglicóis , Proteínas Proto-Oncogênicas B-raf , Animais , Células Dendríticas/imunologia , Células Dendríticas/efeitos dos fármacos , Polietilenoglicóis/química , Proteínas Proto-Oncogênicas B-raf/genética , Melanoma/imunologia , Melanoma/tratamento farmacológico , Nanopartículas/química , Linhagem Celular Tumoral , Camundongos , Imiquimode/farmacologia , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/farmacologia , Feminino , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Liberação Controlada de Fármacos , Humanos , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/prevenção & controle , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
Microsponges are promising drug delivery carriers with versatile characteristics and controlled release properties for the delivery of a wide range of drugs. The microsponges will provide an optimized therapeutic effect, when delivered at the site of action without rupturing, then releasing the cargo at the predetermined time and area. The ability of the microsponges to effectively deliver the drug in a controlled manner depends on the material composition. This comprehensive review entails knowledge on the design parameters of an optimized microsponge drug delivery system and the controlled release properties of microsponges that reduces the side effects of drugs. Furthermore, the review delves into the fabrication techniques of microsponges, the mechanism of drug release from the microsponges, and the regulatory requirements of the U.S. Food and Drug Administration (FDA) for the successful marketing of microsponge formulation. The review also examines the patented formulations of microsponges. The prospects of these sophisticated drug delivery systems for improved clinical outcomes are highlighted.
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Portadores de Fármacos , Humanos , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Preparações de Ação Retardada/química , AnimaisRESUMO
This review highlights the transformative impact of microfluidic technology on personalized drug delivery. Microfluidics addresses issues in traditional drug synthesis, providing precise control and scalability in nanoparticle fabrication, and microfluidic platforms show high potential for versatility, offering patient-specific dosing and real-time monitoring capabilities, all integrated into wearable technology. Covalent conjugation of antibodies to nanoparticles improves bioactivity, driving innovations in drug targeting. The integration of microfluidics with sensor technologies and artificial intelligence facilitates real-time feedback and autonomous adaptation in drug delivery systems. Key challenges, such as droplet polydispersity and fluidic handling, along with future directions focusing on scalability and reliability, are essential considerations in advancing microfluidics for personalized drug delivery.
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Microfluídica , Dispositivos Eletrônicos Vestíveis , Humanos , Inteligência Artificial , Reprodutibilidade dos Testes , Sistemas de Liberação de MedicamentosRESUMO
Human skin is the largest organ and outermost surface of the human body, and due to the continuous exposure to various challenges, it is prone to develop injuries, customarily known as wounds. Although various tissue engineering strategies and bioactive wound matrices have been employed to speed up wound healing, scarring remains a significant challenge. The wound environment is harsh due to the presence of degradative enzymes and elevated pH levels, and the physiological processes involved in tissue regeneration operate on distinct time scales. Therefore, there is a need for effective drug delivery systems (DDSs) to address these issues. The objective of this review is to provide a comprehensive exposition of the mechanisms underlying the skin healing process, the factors and materials used in engineering DDSs, and the different DDSs used in wound care. Furthermore, this investigation will delve into the examination of emergent technologies and potential avenues for enhancing the efficacy of wound care devices.
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Pele , Cicatrização , Humanos , Pele/patologia , Cicatriz/patologia , Engenharia Tecidual , Sistemas de Liberação de MedicamentosRESUMO
In this review, we highlight the potential of stimuli-responsive drug delivery systems (DDSs) to revolutionize healthcare. Through examining pH, temperature, enzyme, and redox responsiveness, the presented case studies highlight the precision and enhanced therapeutic outcomes achievable with these innovative systems. Challenges, such as complex design and bio-based material optimization, underscore the complete journey from bench to bedside. Clinical strides in magnetically and temperature-responsive systems hint at a promising future for healthcare. However, overcoming issues of stability, durability, penetration depth, sensitivity, and active targeting is crucial. The future envisions theranostic systems, amalgamating targeted therapy and diagnosis, for personalized healthcare. Bio-based materials emerge as pivotal, offering a nuanced approach to complex diseases, such as cancer and diabetes, reshaping the healthcare landscape.
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Nanopartículas , Neoplasias , Humanos , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Medicina de Precisão , Temperatura , Portadores de Fármacos/uso terapêuticoRESUMO
Guided bone regeneration (GBR) is a promising technique in bone tissue engineering that aims to replace lost or injured bone using resorbable scaffolds. The promotion of osteoblast adhesion, migration, and proliferation is greatly aided by GBR materials, and surface changes are critical in imitating the natural bone structure to improve cellular responses. Moreover, the interactions between bioresponsive scaffolds, growth factors (GFs), immune cells, and stromal progenitor cells are essential in promoting bone regeneration. This literature review comprehensively discusses various aspects of resorbable scaffolds in bone tissue engineering, encompassing scaffold design, materials, fabrication techniques, and advanced manufacturing methods, including three-dimensional printing. In addition, this review explores surface modifications to replicate native bone structures and their impact on cellular responses. Moreover, the mechanisms of bone regeneration are described, providing information on how immune cells, GFs, and bioresponsive scaffolds orchestrate tissue healing. Practical applications in clinical settings are presented to underscore the importance of these principles in promoting tissue integration, healing, and regeneration. Furthermore, this literature review delves into emerging areas of metamaterials and artificial intelligence applications in tissue engineering and regenerative medicine. These interdisciplinary approaches hold immense promise for furthering bone tissue engineering and improving therapeutic outcomes, leading to enhanced patient well-being. The potential of combining material science, advanced manufacturing, and cellular biology is showcased as a pathway to advance bone tissue engineering, addressing a variety of clinical needs and challenges. By providing this comprehensive narrative, a detailed, up-to-date account of resorbable scaffolds' role in bone tissue engineering and their transformative potential is offered.
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Vitamin D is one significant prohormone substance in human organ systems. It is a steroidal hormone produced in the skin upon exposure to UVB rays. This paper presents a systematic review of the utilization of topical vitamin D, specifically cholecalciferol, calcipotriol, and tacalcitol, in the treatment of vitiligo. It considers the role of vitamin D in stimulating the synthesis of melanin and melanogenesis, which can help with the process of repigmentation. The inclusion of calcipotriol or tacalcitol in Narrowband Ultraviolet Phototherapy (NB-UVB) has shown the potential to enhance therapeutic outcomes for vitiligo. However, their effectiveness in combination with Psoralens Long Wave Ultraviolet Radiation (PUVA) and Monochromatic Excimer Light (MEL) treatment for vitiligo is limited. In contrast, combining topical corticosteroids with vitamin D analogues has demonstrated superior efficacy in treating vitiligo compared to using vitamin D analogues alone, while also providing the added benefit of reducing corticosteroid-related adverse effects. In addition, treating stable vitiligo with topical cholecalciferol and microneedling has shown success. Future studies are needed to ascertain an efficient method of administering vitamin D topically as an anti-vitiligo agent.
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Terapia Ultravioleta , Vitiligo , Humanos , Vitamina D/uso terapêutico , Vitiligo/tratamento farmacológico , Vitiligo/etiologia , Raios Ultravioleta , Terapia Ultravioleta/efeitos adversos , Terapia Ultravioleta/métodos , VitaminasRESUMO
In this study we examine the influence of wool-derived keratin intermediate filament proteins (kIFPs) on human dental pulp-derived stem cells (hDPSCs). kIFPs were diluted (10 mg/mL to 0.001 mg/mL) in cell culture media. Effects on hDPSCs proliferation were measured using Alamar blue assay. Keratin concentrations of 1 mg/mL and 0.1 mg/mL were tested for odontogenic differentiation and mineralisation. Alkaline phosphatase (ALP) quantification (7th, 14th, and 21st days), alizarin red S (AR-S) staining and calcium quantification (21st day), reverse transcription polymerase chain reaction (RT-PCR, collagen expression), and immunocytochemical staining for dentin matrix protein (DMP) were performed. hDPSCs showed higher proliferation with kIFPs of 0.1 mg/mL or less (p < 0.0001). The 0.1 mg/mL keratin concentration promoted odontogenic differentiation, confirmed by increased ALP activity, significant calcium deposits (AR-S staining, p < 0.05), up-regulated collagen expression (RT-PCR, p < 0.05), and positive DMP staining. These results suggest that kIFPs could be a potential biomaterial for pulp-dentin regeneration.
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Polpa Dentária , Queratinas , Animais , Humanos , Polpa Dentária/metabolismo , Queratinas/metabolismo , Lã , Cálcio/metabolismo , Cálcio/farmacologia , Colágeno/farmacologia , Diferenciação Celular , Células-Tronco/metabolismo , Células Cultivadas , Proliferação de CélulasRESUMO
OBJECTIVE: Because of the anatomical complexity of the oral and maxillofacial sites, repairing bone defects in these regions is very difficult. This review article aims to consider the application of biocomposites-based strategies for dental bone regeneration. STUDY DESIGN: Research papers related to the topic, published over the last 20 years, were selected using the Web of Science, Pubmed, Scopus, and Google Scholar databases. RESULTS: The strategies of monophasic, biphasic/multiphasic scaffolds, and biopolymer-based nanocomposite scaffolds containing nanomaterials compared with traditional methods used for bone regeneration, such as autografts, allografts, xenografts, and alloplasts are found to be superior because of their ability to overcome the issues (e.g., limited bone sources, pain, immune responses, high cost) related to the applications of the traditional methods. CONCLUSIONS: In addition, additive manufacturing technologies were found to be highly advantageous for improving the efficacy of biocomposite scaffolds for treating dental bone defects.
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Regeneração Óssea , Humanos , Regeneração Óssea/fisiologia , Transplante AutólogoRESUMO
Nanomedicine has emerged as a promising therapeutic approach, but its translation to the clinic has been hindered by the lack of cellular models to anticipate how tumor cells will respond to therapy. Three-dimensional (3D) cell culture models are thought to more accurately recapitulate key features of primary tumors than two-dimensional (2D) cultures. Heterotypic 3D tumor spheroids, composed of multiple cell types, have become more popular than homotypic spheroids, which consist of a single cell type, as a superior model for mimicking in vivo tumor heterogeneity and physiology. The stromal interactions demonstrated in heterotypic 3D tumor spheroids can affect various aspects, including response to therapy, cancer progression, nanomedicine penetration, and drug resistance. Accordingly, to design more effective anticancer nanomedicinal therapeutics, not only tumor cells but also stromal cells (e.g., fibroblasts and immune cells) should be considered to create a more physiologically relevant in vivo microenvironment. This review aims to demonstrate current knowledge of heterotypic 3D tumor spheroids in cancer research, to illustrate current advances in utilizing these tumor models as a novel and versatile platform for in vitro evaluation of nanomedicine-based therapeutics in cancer research, and to discuss challenges, guidelines, and future directions in this field.
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Nanomedicina , Esferoides Celulares , Linhagem Celular Tumoral , FibroblastosRESUMO
When developing topical semisolid products, it is crucial to consider the metamorphosis of the formulation under the "in use" condition. Numerous critical quality characteristics, including rheological properties, thermodynamic activity, particle size, globule size, and the rate/extent of drug release/permeation, can be altered during this process. This study aimed to use lidocaine as a model drug to establish a connection between the evaporation and change of rheological properties and the permeation of active pharmaceutical ingredients (APIs) in topical semisolid products under the "in use" condition. The evaporation rate of the lidocaine cream formulation was calculated by measuring the weight loss and heat flow of the sample using DSC/TGA. Changes in rheological properties due to metamorphosis were assessed and predicted using the Carreau-Yasuda model. The impact of solvent evaporation on a drug's permeability was studied by in vitro permeation testing (IVPT) using occluded and unconcluded cells. Overall, it was found that the viscosity and elastic modulus of prepared lidocaine cream gradually increased with the time of evaporation as a result of the aggregation of carbopol micelles and the crystallization of API after application. Compared to occluded cells, the permeability of lidocaine for formulation F1 (2.5% lidocaine) in unoccluded cells decreased by 32.4%. This was believed to be the result of increasing viscosity and crystallization of lidocaine instead of depletion of API from the applied dose, which was confirmed by formulation F2 with a higher content of API (5% lidocaine) showing a similar pattern, i.e., a 49.7% reduction of permeability after 4 h of study. To the best of our knowledge, this is the first study to simultaneously demonstrate the rheological change of a topical semisolid formulation during volatile solvent evaporation, resulting in a concurrent decrease in the permeability of API, which provides mathematical modelers with the necessary background to build complex models that incorporate evaporation, viscosity, and drug permeation in the simulation once at a time.
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Studies have demonstrated the significant role of the thermodynamic activity of drugs in skin drug delivery. This thermodynamic activity works as a driving force for increasing/improving the absorption of drugs by the skin. It can be changed according to the physicochemical parameters (e.g., solubility, partition coefficient, and water activity) of the drug in the vehicle. Thermodynamic principles have been used for the development of novel topical and transdermal delivery systems, demonstrating the importance of thermodynamic activity in enhancing drug permeation through the skin. In this review, we provide insights into thermodynamic principles and their roles in optimizing topical and transdermal drug delivery systems.
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Absorção Cutânea , Pele , Pele/metabolismo , Administração Cutânea , Sistemas de Liberação de Medicamentos , Preparações Farmacêuticas/metabolismo , TermodinâmicaRESUMO
The oral cavity is a complex ecosystem accommodating various microorganisms (e.g., bacteria and fungi). Various factors, such as diet change and poor oral hygiene, can change the composition of oral microbiota, resulting in the dysbiosis of the oral micro-environment and the emergence of pathogenic microorganisms, and consequently, oral infectious diseases. Systemic administration is frequently used for drug delivery in the treatment of diseases and is associated with the problems, such as drug resistance and dysbiosis. To overcome these challenges, oral drug delivery systems (DDS) have received considerable attention. In this literature review, the related articles are identified, and their findings, in terms of current therapeutic challenges and the applications of DDSs, especially nanoscopic DDSs, for the treatment of oral infectious diseases are highlighted. DDSs are also discussed in terms of structures and therapeutic agents (e.g., antibiotics, antifungals, antiviral, and ions) that they deliver. In addition, strategies (e.g., theranostics, hydrogel, microparticle, strips/fibers, and pH-sensitive nanoparticles), which can improve the treatment outcome of these diseases, are highlighted.
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Glioblastoma is an incurable cancer with a 5-year survival chance of less than 5%. Chemotherapy is a therapeutic approach to treating the disease; however, due to the presence of the blood-brain barrier (BBB), the probability of success is low. To overcome this issue, nanoparticles are promising carriers for crossing the BBB and delivering drugs to the tumor. In this study, the anticancer efficacy of doxorubicin (DOX) and carboplatin (CB) loaded into polyethylene glycol (PEG)ylated liposome nanoparticles (PEG-Lip) and in treating brain cancer was evaluated in vitro and in vivo. The results demonstrated that PEG-Lip-DOX/CB with a size of 212 ± 10 nm was synthesized that could release the loaded drugs in a controlled manner, from which 56.3% of the loaded drugs were released after 52 h. In addition, PEG-Lip-DOX/CB could significantly increase the cytotoxicity effects of the drugs against rat glioma C6 cells (IC50: 8.7 and 12.9 µM for the drugs-loaded nanoparticles and DOX + CB, respectively). The in vivo results also demonstrated that PEGylated liposomes, compared to non-PEGylated liposomes (Lip) and DOX + CB, were more efficient in increasing the therapeutic effects and decreasing the side effects of the drugs, in which the survival times of the glioblastoma-bearing rats were 39, 35, and 30 days in the PEG-Lip-DOX/CB, Lip-DOX/CB, and DOX + CB receiver groups, respectively. In addition, the weight loss was found to be 8.7, 10.5, and 13%, respectively, in the groups. The results of the toxicity evaluation were also confirmed by histopathological studies. Overall, the results of this study demonstrated that the encapsulation of DOX and CB into PEG-Lip is a promising approach to improving the properties of DOX and CB in terms of their therapeutic effects and drug side effects for the treatment of glioblastoma.
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This review focuses on the biomedical application of mesoporous silica nanoparticles (MSNs), mainly focusing on the therapeutic application of MSNs for cancer treatment and specifically on overcoming the challenges of currently available anthelmintics (e.g., low water solubility) as repurposed drugs for cancer treatment. MSNs, due to their promising features, such as tunable pore size and volume, ability to control the drug release, and ability to convert the crystalline state of drugs to an amorphous state, are appropriate carriers for drug delivery with the improved solubility of hydrophobic drugs. The biomedical applications of MSNs can be further improved by the development of MSN-based multimodal anticancer therapeutics (e.g., photosensitizer-, photothermal-, and chemotherapeutics-modified MSNs) and chemical modifications, such as poly ethyleneglycol (PEG)ylation. In this review, various applications of MSNs (photodynamic and sonodynamic therapies, chemotherapy, radiation therapy, gene therapy, immunotherapy) and, in particular, as the carrier of anthelmintics for cancer therapy have been discussed. Additionally, the issues related to the safety of these nanoparticles have been deeply discussed. According to the findings of this literature review, the applications of MSN nanosystems for cancer therapy are a promising approach to improving the efficacy of the diagnostic and chemotherapeutic agents. Moreover, the MSN systems seem to be an efficient strategy to further help to decrease treatment costs by reducing the drug dose.
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Antimicrobial resistance is a major concern for public health throughout the world that severely restricts available treatments. In this context, methicillin-resistant Staphylococcus aureus (MRSA) is responsible for a high percentage of S. aureus infections and mortality. To overcome this challenge, nanoparticles are appropriate tools as drug carriers to improve the therapeutic efficacy and decrease the toxicity of drugs. In this study, a polyethylene glycol (PEG)ylated nanostructured lipid carrier (PEG-NLC) was synthesized to improve the oral delivery of trimethoprim/sulfamethoxazole (TMP/SMZ) for the treatment of MRSA skin infection in vitro and in vivo. The nanoformulation (PEG-TMP/SMZ-NLC) was synthesized with size and drug encapsulation efficiencies of 187 ± 9 nm and 93.3%, respectively, which could release the drugs in a controlled manner at intestinal pH. PEG-TMP/SMZ-NLC was found efficient in decreasing the drugs' toxicity by 2.4-fold in vitro. In addition, the intestinal permeability of TMP/SMZ was enhanced by 54%, and the antibacterial effects of the drugs were enhanced by 8-fold in vitro. The results of the stability study demonstrated that PEG-TMP/SMZ-NLC was stable for three months. In addition, the results demonstrated that PEG-TMP/SMZ-NLC after oral administration could decrease the drugs' side-effects such as renal and hepatic toxicity by ~5-fold in MRSA skin infection in Balb/c mice, while it could improve the antibacterial effects of TMP/SMZ by 3 orders of magnitude. Overall, the results of this study suggest that the application of PEGylated NLC nanoparticles is a promising approach to improving the oral delivery of TMP/SMZ for the treatment of MRSA skin infection.
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This study aimed to characterize a stable nano-niosome formulation, which could reduce the adverse effects of carboplatin (CB) and improve its therapeutic efficacy in the treatment of breast cancer. For this purpose, CB-loaded polyethylene glycol (PEG)ylated niosome nanoparticles (PEG-NS-CB) were synthesized using the reverse-phase evaporation method. PEG-NS-CB (226.0 ± 10.6 nm) could release CB in a controlled manner and, compared to CB and CB-loaded non-PEGylated niosome (NS-CB), caused higher cytotoxicity effects against mouse breast cancer 4T1 cells (IC50: 83.4, 26.6, and 22.5 µM for CB, NS-CB, and PEG-NS-CB, respectively). Also, PEG-NS-CB demonstrated higher stability, in which its profile of drug release, cytotoxicity, and LE% did not change significantly three months after preparation compared to those at the production time. In addition, the in vivo results demonstrated that PEG-NS-CB caused higher therapeutic (the number of alive mice: 12, 15, and 17 out of 20 in CB, NS-CB, and PEG-NS-CB receiver groups, respectively) and less toxicity effects (weight loss of 17, 12.5, and 10% in CB, NS-CB, and PEG-NS-CB receiver groups, respectively), compared to NS-CB and CB in breast cancer-bearing mice. Overall, the results of this study suggest that PEG-NS-CB could be a promising formulation for the treatment of breast cancer.
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Nanopartículas , Neoplasias , Animais , Carboplatina , Linhagem Celular Tumoral , Portadores de Fármacos , Lipossomos , Camundongos , Neoplasias/tratamento farmacológico , PolietilenoglicóisRESUMO
Staphylococcus aureus (S. aureus) biofilm-associated infections are a primary concern for public health worldwide. Current therapeutics cannot penetrate the biofilms efficiently, resulting in low drug concentrations at the infected sites and increasing the frequency of drug usage. To solve this issue, nanotechnology platforms seem to be a promising approach. In this study, the potential therapeutic effects of (PEG)ylated liposome (PEG-Lip) for the delivery of nafcillin (NF) antibiotic were assessed. The results demonstrated that NF-loaded liposome (Lip-NF) and NF-loaded PEG-Lip (PEG-Lip-NF) released 76.4 and 62% of the loaded NF, respectively, in a controlled manner after 50 h. Also, it was found that PEG-Lip-NF, compared to Lip-NF and NF, was more effective against a methicillin-susceptible S. aureus (MSSA; minimum inhibitory concentration (MIC): 1.0 ± 0.03, 0.5 ± 0.02, and 0.25 ± 0.01 µg/mL; and minimum biofilm inhibitory concentration (MBIC50): 4.0 ± 0.18, 1.0 ± 0.04, and 0.5 ± 0.02 µg/mL for NF, Lip-NF, and PEG-Lip-NF, respectively). PEG-Lip-NF, compared to NF and Lip-NF, could also more efficiently decrease the side effects of NF through improving human MG-63 osteoblast cell viability (cell viability at 100 µM of NF: 76, 68, and 38% for PEG-Lip-NF, Lip-NF, and NF, respectively). PEG-Lip-NF, compared to control, NF, and Lip-NF groups, was more efficacious by 45, 25, and 10%, respectively, to decrease the virulence of MSSA bacteremia through inhibiting the weight loss of the infected mice. Also, PEG-Lip-NF and Lip-NF, compared to control and NF groups, caused a considerable decrease in the mortality rate in a murine model of bacteremia (number of dead mice: 0, 0, 2, and 8 out of 15 for PEG-Lip-NF, Lip-NF, NF, and control groups, respectively). Overall, the results of this study demonstrated that the loading of NF into PEG-Lip is a promising strategy to decrease the side effects of NF with improved antibacterial effects for the treatment of MSSA biofilm-associated infections.
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Bacteriemia , Infecções Estafilocócicas , Animais , Antibacterianos/farmacologia , Bacteriemia/microbiologia , Lipossomos/farmacologia , Camundongos , Nafcilina/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureusRESUMO
The clinical utilization of fenbendazole (FBZ) as a potential anticancer drug has been limited due to its low water solubility, which causes its low bioavailability. The development of a drug nanoformulation that includes the solubilizing agent as a drug carrier can improve solubility and bioavailability. In this study, Mobil Composition of Matter Number 48 (MCM-48) nanoparticles were synthesized and functionalized with succinylated ß-lactoglobulin (BLG) to prevent early-burst drug release. The BLG-modified amine-functionalized MCM-48 (MCM-BLG) nanoparticles were loaded with FBZ to produce the drug nanoformulation (FBZ-MCM-BLG) and improved the water solubility and, consequently, its anticancer effects against human prostate cancer PC-3 cells. The prepared FBZ-MCM-BLG was characterized in terms of size, zeta potential, drug loading capacity, morphology, thermal and chemical analyses, drug release, cellular uptake, cell viability, cell proliferation, production of reactive oxygen species (ROS), and cell migration. The results demonstrated that the FBZ-MCM-BLG nanoparticles have a spherical morphology with a size and zeta potential of 369 ± 28 nm and 28 ± 0.4 mV, respectively. The drug loading efficiency of the new nanoformulation was 19%. The release of FBZ was pH-dependent; a maximum cumulative release of about 76 and 62% in 12 h and a burst release of 53 and 38% in the first 0.5 h was observed at pH 1.2 and 6.8, respectively. The prepared FBZ-MCM-BLG formulation demonstrated higher cytotoxicity effects against PC-3 cells by 5.6- and 1.8-fold, respectively, when compared to FBZ and FBZ-MCM nanoparticles. The new formulation also increased the production of ROS by 1.6- and 1.2-fold and inhibited the migration of PC-3 cells when compared to the FBZ and FBZ-MCM nanoparticles, respectively. Overall, FBZ-MCM-BLG nanoparticles improved FBZ delivery to PC-3 cells and have the potential to be evaluated for the treatment of prostate cancer following a comprehensive in vivo study.
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The present study aimed to synthesize albendazole (ABZ)-loaded Mobil Composition of Matter No. 41 (MCM-41 NPs) to increase the efficacy of the drug against liver cancer. ABZ was loaded into MCM-41 NPs, and after in vitro characterization, such as size, size distribution, zeta potential, morphology, chemical composition, thermal profile, drug release, surface and pore volume, and pore size, their biological effects were evaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) cell migration assays. The results demonstrated that monodispersed and spherical NPs with a size of 220 ± 11.5 and 293 ± 8.7 nm, for MCM-41 NPs and ABZ-loaded MCM-41 NPs, respectively, and drug loading efficiency of 30 % were synthesized. ABZ was loaded physically into MCM-41 NPs, leading to a decrease in surface volume, pore size, and pore volume. Also, MCM-41 NPs could increase the cytotoxicity effects of ABZ by 2.9-fold (IC50 = 23 and 7.9 µM for ABZ and ABZ-loaded MCM-41 NPs, respectively). In addition, both ABZ and ABZ-loaded MCM-41 NPs could restrain the cell migration by 12 %. Overall, the results of the present study suggest evaluating the potency of MCM-41 NPs, as a potent nanoplatform, for ABZ delivery in vivo environment. See also the Graphical Abstract(Fig. 1).