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1.
Microvasc Res ; 157: 104743, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39260680

RESUMO

PURPOSE: To compare differences in the foveal avascular zone (FAZ) area, measured in the Superficial Vascular Complex (SVC), Deep Vascular Complex (DVC) and a combined analysis of both (SDVC), using two Spectral Domain OCT angiography (OCT-A) protocols, High Speed (HS) and High Resolution (HR). METHODS: A total of 26 eyes of diabetic patients, with and without macular oedema, were examined with two different fovea centered OCT-A volume scans. The two protocols were HS and HR volume scans, and the foveal avascular zone was manually measured in the SVC, DVC, and SDVC slabs by two masked investigators. Inter and intraoperator variability was analysed using Intraclass Correlation Coefficient (ICC) and differences were compared between the HR and HS acquisitions throughout the different vascular slabs. RESULTS: Intraoperator variability was low in all slabs (ICC > 0.9) and interoperator variability was lower for HR (ICC 0.835-0.911) compared to HS (ICC between 0.604 and 0.865). Comparing HS and HR measurements for the same slab, the correlation was only moderate in SVC and DVC (ICC was 0.640 and 0.568 respectively) but was good in the SDVC (ICC = 0.823). FAZ area measurement in SDVC also showed the smallest bias (mean difference 0.009 mm2) and the narrowest limits of agreement (-0.175 to 0.193 mm2). CONCLUSIONS: Even in cases of diabetic macular oedema, when measuring the FAZ area, the reproducibility was better between HS and HR protocols when using the SDVC slab, compared to the SVC or DVC slabs alone. Further studies should evaluate the use of the combined SDVC slab for the FAZ assessment, compared to the SVC and DVC slabs alone, in the detection and progression of different retinal diseases.

2.
Int J Mol Sci ; 25(17)2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39273469

RESUMO

Most chemotherapeutic agents are poorly soluble in water, have low selectivity, and cannot reach the tumor in the desired therapeutic concentration. On the other hand, sensitive hydrophilic therapeutics like nucleic acids and proteins suffer from poor bioavailability and cell internalization. To solve this problem, new types of controlled release systems based on nano-sized self-assemblies of cyclodextrins able to control the speed, timing, and location of therapeutic release are being developed. Cyclodextrins are macrocyclic oligosaccharides characterized by a high synthetic plasticity and potential for derivatization. Introduction of new hydrophobic and/or hydrophilic domains and/or formation of nano-assemblies with therapeutic load extends the use of CDs beyond the tried-and-tested CD-drug host-guest inclusion complexes. The recent advances in nano drug delivery have indicated the benefits of the hybrid amphiphilic CD nanosystems over individual CD and polymer components. This review provides a comprehensive overview of the most recent advances in the design of CDs self-assemblies and their use for delivery of a wide range of therapeutic molecules. It aims to offer a valuable insight into the many roles of CDs within this class of drug nanocarriers as well as current challenges and future perspectives.


Assuntos
Ciclodextrinas , Portadores de Fármacos , Polímeros , Ciclodextrinas/química , Humanos , Polímeros/química , Portadores de Fármacos/química , Nanopartículas/química , Sistemas de Liberação de Medicamentos , Interações Hidrofóbicas e Hidrofílicas , Animais
3.
Cureus ; 16(8): e66963, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39280378

RESUMO

Brugada syndrome (BS) is characterized by abnormal repolarization in cardiac cells, occurring in the absence of structural heart disease, which elevates the risk of ventricular arrhythmias and sudden cardiac death. While most BS patients are asymptomatic, a notable percentage experience syncope or sudden cardiac death. Diagnosis is primarily based on electrocardiographic (ECG) findings. A 40-year-old male with a history of syncope and a family history of sudden cardiac death was scheduled for urgent clavicle osteosynthesis. Preoperative ECG revealed type 1 BS. A multidisciplinary approach was taken, and anesthetic management involved combined general and regional anesthesia, utilizing ultrasound-guided clavipectoral and superficial cervical blocks. Postoperative pain was managed with paracetamol and ketorolac. The patient remained stable throughout the procedure, was monitored for 36 hours postoperatively, and was discharged without complications. BS poses significant perioperative risks, necessitating careful anesthetic management. This case report highlights the successful use of combined general and regional anesthesia in a BS patient, contributing to the limited evidence on safe anesthesia practices for this pathology.

4.
Cureus ; 16(7): e64071, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39114213

RESUMO

Obstetric haemorrhage is a leading cause of maternal morbidity and mortality and is a common reason for intensive care unit (ICU) admission in the postpartum. Primary postpartum obstetric haemorrhage is associated with four main causes: tone, thrombin, trauma, and tissue. Regarding the last one, placenta accreta is an abnormal invasion of the placenta into the myometrium. Early diagnosis of placenta accreta allows for better perioperative management; however, it is sometimes only identified during caesarean delivery when the placenta cannot be removed. We report a case of a 37-year-old woman with a history of caesarean section due to placenta previa, who was admitted at 36 weeks and 1 day for an urgent caesarean section (c-section) due to cord presentation. A subarachnoid block (SAB) was used for anaesthesia. It was chosen over general anaesthesia because it allows the patient to experience the birth of her children, enhances pain control, and avoids complications associated with general anaesthesia. Besides our centre has expertise in neuraxial anaesthesia. During the procedure, placental accretism and massive haemorrhage occurred, and a life-saving abdominal hysterectomy was needed. The patient experienced hypotension, partially responsive to volume replacement and vasopressors, leading to norepinephrine infusion and conversion to general anaesthesia. The surgery lasted 2.5 hours with a blood loss of 3500 ml. The patient was extubated without complications and transferred to the post anaesthesia care unit (PACU). Risk factors for placenta accreta spectrum (PAS) include previous surgery and placenta previa with a prior c-section. Antenatal diagnosis is crucial, and women with risk factors should undergo imaging at experienced centres. Delivery centres must have protocols for unexpected PAS and major obstetric haemorrhage. Both general and neuraxial anaesthesia can be suitable for managing PAS, and caesarean hysterectomy is often required to control haemorrhage. Postoperatively, adequate monitoring and care is essential. PAS management should involve excellent communication between a multidisciplinary team in specialised centres.

5.
Int J Mol Sci ; 25(14)2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-39062820

RESUMO

Colorectal cancer (CRC) is the third most prominent cancer worldwide, and the second leading cause of cancer death. Poor outcomes and limitations of current treatments fuel the search for new therapeutic options. Curcumin (CUR) is often presented as a safer alternative for cancer treatment with a staggering number of molecular targets involved in tumor initiation, promotion, and progression. Despite being promising, its therapeutic potential is hindered due to its hydrophobic nature. Hence, the ongoing development of optimal delivery strategies based on nanotechnology, such as polymeric micelles (PMs), to overcome issues in CUR solubilization and delivery to tumor cells. In this sense, this study aimed to optimize the development and stability of CUR-loaded P123:F127:TPGS PMs (PFT:CUR) based on the thin-film approach and evaluate their therapeutic potential in CRC. Overall, the results revealed that the solubility of CUR was improved when room temperature was used to hydrate the film. The PFT-CUR hydrated at room temperature presents an average hydrodynamic diameter of 15.9 ± 0.3 nm with a polydispersity index (PDI) of 0.251 ± 0.103 and a zeta potential of -1.5 ± 1.9 mV, and a 35.083 ± 1.144 encapsulation efficiency (EE%) and 3.217 ± 0.091 drug loading (DL%) were observed. To ensure the stability of the optimized PFT-CUR nanosystems, different lyophilization protocols were tested, the use of 1% of glycine (GLY) being the most promising protocol. Regarding the critical micellar concentration (CMC), it was shown that the cryoprotectant and the lyophilization process could impact it, with an increase from 0.064 mg/mL to 0.119 mg/mL. In vitro results showed greater cytotoxic effects when CUR was encapsulated compared to its free form, yet further analysis revealed the heightened cytotoxicity could be attributed to the system itself. Despite challenges, the developed CUR-loaded PM shows potential as an effective therapeutic agent for CRC. Nonetheless, the system must undergo refinements to enhance drug entrapment as well as improve overall stability.


Assuntos
Neoplasias Colorretais , Curcumina , Micelas , Vitamina E , Curcumina/química , Curcumina/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Humanos , Vitamina E/química , Portadores de Fármacos/química , Poloxaleno/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Solubilidade , Polímeros/química , Liberação Controlada de Fármacos
6.
Materials (Basel) ; 17(2)2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38255485

RESUMO

Polymersomes are artificial nanoparticles formed by the self-assembly process of amphiphilic block copolymers composed of hydrophobic and hydrophilic blocks. They can encapsulate hydrophilic molecules in the aqueous core and hydrophobic molecules within the membrane. The composition of block copolymers can be tuned, enabling control of characteristics and properties of formed polymersomes and, thus, their application in areas such as drug delivery, diagnostics, or bioimaging. The preparation methods of polymersomes can also impact their characteristics and the preservation of the encapsulated drugs. Many methods have been described, including direct hydration, thin film hydration, electroporation, the pH-switch method, solvent shift method, single and double emulsion method, flash nanoprecipitation, and microfluidic synthesis. Considering polymersome structure and composition, there are several types of polymersomes including theranostic polymersomes, polymersomes decorated with targeting ligands for selective delivery, stimuli-responsive polymersomes, or porous polymersomes with multiple promising applications. Due to the shortcomings related to the stability, efficacy, and safety of some therapeutics in the human body, polymersomes as drug delivery systems have been good candidates to improve the quality of therapies against a wide range of diseases, including cancer. Chemotherapy and immunotherapy can be improved by using polymersomes to deliver the drugs, protecting and directing them to the exact site of action. Moreover, this approach is also promising for targeted delivery of biologics since they represent a class of drugs with poor stability and high susceptibility to in vivo clearance. However, the lack of a well-defined regulatory plan for polymersome formulations has hampered their follow-up to clinical trials and subsequent market entry.

7.
Int J Pharm ; 646: 123456, 2023 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-37778515

RESUMO

Colorectal cancer (CRC) is one of the most common causes of death in the world. The multi-drug resistance, especially in metastatic colorectal cancer, drives the development of new strategies that secure a positive outcome and reduce undesirable side effects. Nanotechnology has made an impact in addressing some pharmacokinetic and safety issues related to administration of free therapeutic agents. However, demands of managing complex biointerfacing require equally complex methods for introducing stimuli-responsive or targeting elements. In order to procure a more efficient solution to the overcoming of biological barriers, the physiological functions of cancer cell plasma and exosomal membranes provided the source of highly functionalized coatings. Biomimetic nanovehicles based on colorectal cancer (CRC) membranes imparted enhanced biological compatibility, immune escape and protection to diverse classes of therapeutic molecules. When loaded with therapeutic load or used as a coating for other therapeutic nanovehicles, they provide highly efficient and selective cell targeting and uptake. This review presents a detailed overview of the recent application of homotypic biomimetic nanovehicles in the management of CRC. We also address some of the current possibilities and challenges associated with the CRC membrane biomimetics.


Assuntos
Neoplasias Colorretais , Exossomos , Humanos , Exossomos/metabolismo , Membrana Celular/metabolismo , Sistemas de Liberação de Medicamentos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo
8.
Pharmaceutics ; 15(10)2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37896191

RESUMO

The paradigm of pediatric drug development has been evolving in a "carrot-and-stick"-based tactic to address population-specific issues. However, the off-label prescription of adult medicines to pediatric patients remains a feature of clinical practice, which may compromise the age-appropriate evaluation of treatments. Therefore, the United States and the European Pediatric Formulation Initiative have recommended applying nanotechnology-based delivery systems to tackle some of these challenges, particularly applying inorganic, polymeric, and lipid-based nanoparticles. Connected with these, advanced therapy medicinal products (ATMPs) have also been highlighted, with optimistic perspectives for the pediatric population. Despite the results achieved using these innovative therapies, a workforce that congregates pediatric patients and/or caregivers, healthcare stakeholders, drug developers, and physicians continues to be of utmost relevance to promote standardized guidelines for pediatric drug development, enabling a fast lab-to-clinical translation. Therefore, taking into consideration the significance of this topic, this work aims to compile the current landscape of pediatric drug development by (1) outlining the historic regulatory panorama, (2) summarizing the challenges in the development of pediatric drug formulation, and (3) delineating the advantages/disadvantages of using innovative approaches, such as nanomedicines and ATMPs in pediatrics. Moreover, some attention will be given to the role of pharmaceutical technologists and developers in conceiving pediatric medicines.

9.
J Pharm Biomed Anal ; 232: 115421, 2023 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-37146495

RESUMO

Amatoxins are toxic bicyclic octapeptides found in certain wild mushroom species, particularly Amanita phalloides. These mushrooms contain predominantly α- and ß-amanitin, which can lead to severe health risks for humans and animals if ingested. Rapid and accurate identification of these toxins in mushroom and biological samples is crucial for diagnosing and treating mushroom poisoning. Analytical methods for the determination of amatoxins are critical to ensure food safety and prompt medical treatment. This review provides a comprehensive overview of the research literature on the determination of amatoxins in clinical specimens, biological and mushroom samples. We discuss the physicochemical properties of toxins, highlighting their influence on the choice of the analytical method and the importance of sample preparation, particularly solid-phase extraction with cartridges. Chromatographic methods are emphasised with a focus on liquid chromatography coupled to mass spectrometry as one of the most relevant analytical method for the determination of amatoxins in complex matrices. Furthermore, current trends and future perspectives in amatoxin detection are also suggested.


Assuntos
Intoxicação Alimentar por Cogumelos , Toxinas Biológicas , Humanos , Animais , Cromatografia Líquida de Alta Pressão/métodos , Intoxicação Alimentar por Cogumelos/diagnóstico , Cromatografia Líquida , Espectrometria de Massas
10.
Vaccines (Basel) ; 11(3)2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36992076

RESUMO

The human microbiota comprises a group of microorganisms co-existing in the human body. Unbalanced microbiota homeostasis may impact metabolic and immune system regulation, shrinking the edge between health and disease. Recently, the microbiota has been considered a prominent extrinsic/intrinsic element of cancer development and a promising milestone in the modulation of conventional cancer treatments. Particularly, the oral cavity represents a yin-and-yang target site for microorganisms that can promote human health or contribute to oral cancer development, such as Fusobacterium nucleatum. Moreover, Helicobacter pylori has also been implicated in esophageal and stomach cancers, and decreased butyrate-producing bacteria, such as Lachnospiraceae spp. and Ruminococcaceae, have demonstrated a protective role in the development of colorectal cancer. Interestingly, prebiotics, e.g., polyphenols, probiotics (Faecalibacterium, Bifidobacterium, Lactobacillus, and Burkholderia), postbiotics (inosine, butyrate, and propionate), and innovative nanomedicines can modulate antitumor immunity, circumventing resistance to conventional treatments and could complement existing therapies. Therefore, this manuscript delivers a holistic perspective on the interaction between human microbiota and cancer development and treatment, particularly in aerodigestive and digestive cancers, focusing on applying prebiotics, probiotics, and nanomedicines to overcome some challenges in treating cancer.

11.
Int J Mol Sci ; 24(3)2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36769299

RESUMO

Coronavirus disease-19 (COVID-19) emerged in December 2019 and quickly spread, giving rise to a pandemic crisis. Therefore, it triggered tireless efforts to identify the mechanisms of the disease, how to prevent and treat it, and to limit and hamper its global dissemination. Considering the above, the search for prophylactic approaches has led to a revolution in the reglementary pharmaceutical pipeline, with the approval of vaccines against COVID-19 in an unprecedented way. Moreover, a drug repurposing scheme using regulatory-approved antiretroviral agents is also being pursued. However, their physicochemical characteristics or reported adverse events have sometimes limited their use. Hence, nanotechnology has been employed to potentially overcome some of these challenges, particularly cyclodextrins. Cyclodextrins are cyclic oligosaccharides that present hydrophobic cavities suitable for complexing several drugs. This review, besides presenting studies on the inclusion of antiviral drugs in cyclodextrins, aims to summarize some currently available prophylactic and therapeutic schemes against COVID-19, highlighting those that already make use of cyclodextrins for their complexation. In addition, some new therapeutic approaches are underscored, and the potential application of cyclodextrins to increase their promising application against COVID-19 will be addressed. This review describes the instances in which the use of cyclodextrins promotes increased bioavailability, antiviral action, and the solubility of the drugs under analysis. The potential use of cyclodextrins as an active ingredient is also covered. Finally, toxicity and regulatory issues as well as future perspectives regarding the use of cyclodextrins in COVID-19 therapy will be provided.


Assuntos
COVID-19 , Ciclodextrinas , Humanos , Vacinas contra COVID-19/uso terapêutico , Ciclodextrinas/farmacologia , Ciclodextrinas/uso terapêutico , Ciclodextrinas/química , Reposicionamento de Medicamentos , Antivirais/farmacologia , Antivirais/uso terapêutico
12.
Polymers (Basel) ; 14(23)2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36501709

RESUMO

Copolymers composed of low-molecular-weight polyethylenimine (PEI) and amphiphilic Pluronics® are safe and efficient non-viral vectors for pDNA transfection. A variety of Pluronic® properties provides a base for tailoring transfection efficacy in combination with the unique biological activity of this polymer group. In this study, we describe the preparation of new copolymers based on hydrophilic Pluronic® F68 and PEI (F68PEI). F68PEI polyplexes obtained by doping with free F68 (1:2 and 1:5 w/w) allowed for fine-tuning of physicochemical properties and transfection activity, demonstrating improved in vitro transfection of the human bone osteosarcoma epithelial (U2OS) and oral squamous cell carcinoma (SCC-9) cells when compared to the parent formulation, F68PEI. Although all tested systems condensed pDNA at varying polymer/DNA charge ratios (N/P, 5/1−100/1), the addition of free F68 (1:5 w/w) resulted in the formation of smaller polyplexes (<200 nm). Analysis of polyplex properties by transmission electron microscopy and dynamic light scattering revealed varied polyplex morphology. Transfection potential was also found to be cell-dependent and significantly higher in SCC-9 cells compared to the control bPEI25k cells, as especially evident at higher N/P ratios (>25). The observed selectivity towards transfection of SSC-9 cells might represent a base for further optimization of a cell-specific transfection vehicle.

13.
Foods ; 11(23)2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36496736

RESUMO

Mushroom poisoning remains a serious food safety and health concern in some parts of the world due to its morbidity and mortality. Identification of mushroom toxins at an early stage of suspected intoxication is crucial for a rapid therapeutic decision. In this study, a new extraction method was developed to determine α- and ß-amanitin in mushroom samples collected from central Portugal. High-performance liquid chromatography with in-line ultraviolet and electrochemical detection was implemented to improve the specificity of the method. The method was fully validated for linearity (0.5-20.0 µg·mL-1), sensitivity, recovery, and precision based on a matrix-matched calibration method. The limit of detection was 55 µg mL-1 (UV) and 62 µg mL-1 (EC) for α-amanitin and 64 µg mL-1 (UV) and 24 µg mL-1 (EC) for ß-amanitin. Intra- and inter-day precision differences were less than 13%, and the recovery ratios ranged from 89% to 117%. The developed method was successfully applied to fourteen Amanita species (A. sp.) and compared with five edible mushroom samples after extraction with Oasis® PRIME HLB cartridges without the conditioning and equilibration step. The results revealed that the A. phalloides mushrooms present the highest content of α- and ß-amanitin, which is in line with the HPLC-DAD-MS. In sum, the developed analytical method could benefit food safety assessment and contribute to food-health security, as it is rapid, simple, sensitive, accurate, and selectively detects α- and ß-amanitin in any mushroom samples.

14.
Pharmaceutics ; 14(8)2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-36015325

RESUMO

In the last decade, nanomedicine has arisen as an emergent area of medicine, which studies nanometric systems, namely polymeric micelles (PMs), that increase the solubility and the stability of the encapsulated drugs. Furthermore, their application in dermal drug delivery is also relevant. PMs present unique characteristics because of their unique core-shell architecture. They are colloidal dispersions of amphiphilic compounds, which self-assemble in an aqueous medium, giving a structure-type core-shell, with a hydrophobic core (that can encapsulate hydrophobic drugs), and a hydrophilic shell, which works as a stabilizing agent. These features offer PMs adequate steric protection and determine their hydrophilicity, charge, length, and surface density properties. Furthermore, due to their small size, PMs can be absorbed by the intestinal mucosa with the drug, and they transport the drug in the bloodstream until the therapeutic target. Moreover, PMs improve the pharmacokinetic profile of the encapsulated drug, present high load capacity, and are synthesized by a reproducible, easy, and low-cost method. In silico approaches have been explored to improve the physicochemical properties of PMs. Based on this, a computer-aided strategy was developed and validated to enable the delivery of poorly soluble drugs and established critical physicochemical parameters to maximize drug loading, formulation stability, and tumor exposure. Poly(2-oxazoline) (POx)-based PMs display unprecedented high loading concerning water-insoluble drugs and over 60 drugs have been incorporated in POx PMs. Among various stimuli, pH and temperature are the most widely studied for enhanced drug release at the site of action. Researchers are focusing on dual (pH and temperature) responsive PMs for controlled and improved drug release at the site of action. These dual responsive systems are mainly evaluated for cancer therapy as certain malignancies can cause a slight increase in temperature and a decrease in the extracellular pH around the tumor site. This review is a compilation of updated therapeutic applications of PMs, such as PMs that are based on Pluronics®, micelleplexes and Pox-based PMs in several biomedical applications.

15.
Int J Mol Sci ; 23(15)2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35955712

RESUMO

The fast advancement in nanotechnology has prompted the improvement of numerous methods for the creation of various nanoscale composites of which nanofibers have gotten extensive consideration. Nanofibers are polymeric/composite fibers which have a nanoscale diameter. They vary in porous structure and have an extensive area. Material choice is of crucial importance for the assembly of nanofibers and their function as efficient drug and biomedicine carriers. A broad scope of active pharmaceutical ingredients can be incorporated within the nanofibers or bound to their surface. The ability to deliver small molecular drugs such as antibiotics or anticancer medications, proteins, peptides, cells, DNA and RNAs has led to the biomedical application in disease therapy and tissue engineering. Although nanofibers have shown incredible potential for drug and biomedicine applications, there are still difficulties which should be resolved before they can be utilized in clinical practice. This review intends to give an outline of the recent advances in nanofibers, contemplating the preparation methods, the therapeutic loading and release and the various therapeutic applications.


Assuntos
Nanofibras , Sistemas de Liberação de Medicamentos/métodos , Nanofibras/química , Nanotecnologia , Polímeros/química , Engenharia Tecidual/métodos
16.
ACS Nano ; 16(7): 9994-10041, 2022 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-35729778

RESUMO

Worldwide nanotechnology development and application have fueled many scientific advances, but technophilic expectations and technophobic demands must be counterbalanced in parallel. Some of the burning issues today are the following: (1) Where is nano today? (2) How good are the communication and investment networks between academia/research and governments? (3) Is there any spotlight application for nanotechnology? Nanomedicine is a particular arm of nanotechnology within the healthcare landscape, focused on diagnosis, treatment, and monitoring of emerging (such as coronavirus disease 2019, COVID-19) and contemporary (including diabetes, cardiovascular diseases, neurodegenerative disorders, and cancer) diseases. However, it may only represent the bright side of the coin. In fact, in the recent past, the concept of nanotoxicology has emerged to address the dark shadows of nanomedicine. The nanomedicine field requires more nanotoxicological studies to identify undesirable effects and guarantee safety. Here, we provide an overall perspective on nanomedicine and nanotoxicology as central pieces of the giant puzzle of nanotechnology. First, the impact of nanotechnology on education and research is highlighted, followed by market trends and scientific output tendencies. In the next section, the nanomedicine and nanotoxicology dilemma is addressed through the interplay of in silico, in vitro, and in vivo models with the support of omics and microfluidic approaches. Lastly, a reflection on the regulatory issues and clinical trials is provided. Finally, some conclusions and future perspectives are proposed for a clearer and safer translation of nanomedicines from the bench to the bedside.


Assuntos
Tratamento Farmacológico da COVID-19 , Nanopartículas , Neoplasias , Humanos , Nanomedicina , Nanopartículas/efeitos adversos , Nanotecnologia , Neoplasias/tratamento farmacológico
17.
Eur J Pharm Biopharm ; 170: 91-111, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34896571

RESUMO

The most common primary malignant tumor of bone in children is osteosarcoma (OS). Nowadays, the prognosis and the introduction of chemotherapy in OS have improved survival rates of patients. Nevertheless, the results are still unsatisfactory, especially, in patients with recurrent disease or metastatic. OS chemotherapy has two main challenges related to treatment toxicity and multiple drug resistance. In this way, nanotechnology has developed nanosystems capable of releasing the drug directly at the OS cells and decreasing the drug's toxicity. Exosomes (Exo), a cell-derived nano-sized and a phospholipid vehicle, have been recognized as important drug delivery systems in several cancers. They are involved in a variety of biological processes and are an important mediator of long-distance intercellular communication. Exo can reduce inflammation and show low toxicity in healthy cells. Furthermore, the incorporation of specific proteins or peptides on the Exo surface improves their targeting capability in several clinical applications. Due to their unique structure and relevant characteristics, Exo is a promising nanocarrier for OS treatment. This review intends to describe the properties that turn Exo into an efficient, as well as safe nanovesicle for drug delivery and treatment of OS.


Assuntos
Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Portadores de Fármacos , Exossomos/metabolismo , Osteossarcoma/tratamento farmacológico , Antineoplásicos/administração & dosagem , Comunicação Celular , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos , Humanos , Nanopartículas
18.
Surg Innov ; 29(2): 225-233, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34266340

RESUMO

Background. Scar appearance is an important outcome in abdominoplasty surgery, and its asymmetry can have a significant impact on patient and surgeon satisfaction. Here, we compared the scar symmetry reached with a ruler specially designed for the preoperative marking in abdominoplasty to the classic preoperative incision marking. Methods. In this randomized, uni-blind study, 42 patients were allocated to 2 different groups. Group 1 patients had their preoperative marking made by a group of surgeons that used the classic technique as described by Baroudi (n = 21), and Group 2 patients received their preoperative marking by another group of surgeons, using a ruler specially designed to fit the abdominal contour (n = 21). Patients were evaluated using a standard questionnaire that collected information about general patient's characteristics. On the follow-up period, we evaluated the presence of late surgical complications, need for revision surgery, patient's satisfaction concerning the postoperative scar, and 4 distances were measured in both groups to assess symmetry. Statistical analysis was made. Results. A total of 42 patients underwent abdominoplasty and were evaluated on the follow-up period (mean time: 4 months). The mean difference of corresponding measures on each side (A-B vs. A-B' and A-C vs. A-C') was higher in Group 1 comparing to Group 2. The level of correlation between corresponding measurements was higher in Group 2. Better satisfaction regarding the scar symmetry was achieved in Group 2, being this result statistically significant (P = .004). Conclusions. The use of the specialized ruler may help surgeons achieve a better scar symmetry with higher patient satisfaction.


Assuntos
Abdominoplastia , Cicatriz , Abdome/cirurgia , Abdominoplastia/métodos , Cicatriz/prevenção & controle , Humanos , Satisfação do Paciente , Complicações Pós-Operatórias/etiologia , Reoperação , Estudos Retrospectivos
19.
Int J Pharm ; 597: 120362, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33556489

RESUMO

The decoding of the human genome revolutionized the understanding of how genetics influence the interplay between health and disease, in a multidisciplinary perspective. Thus, the development of exogenous nucleic acids-based therapies has increased to overcome hereditary or acquired genetic-associated diseases. Gene drug delivery using non-viral systems, for instance micelleplexes, have been recognized as promising options for gene-target therapies. Micelleplexes are core-shell structures, at a nanometric scale, designed using amphiphilic block copolymers. These can self-assemble in an aqueous medium, leading to the formation of a hydrophilic and positively charged corona - that can transport nucleic acids, - and a hydrophobic core - which can transport poor water-soluble drugs. However, the performance of these types of carriers usually is hindered by several in vivo barriers. Fortunately, due to a significant amount of research, strategies to overcome these shortcomings emerged. With a wide range of structural features, good stability against proteolytic degradation, affordable characteristic, easy synthesis, low immunogenicity, among other advantages, peptides have increasingly gained popularity as target ligands for non-viral carriers. Hence, this review addresses the use of peptides with micelleplexes illustrating, through the analysis of in vitro and in vivo studies, the potential and future perspectives of this combination.


Assuntos
Micelas , Polímeros , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Técnicas de Transferência de Genes , Humanos , Interações Hidrofóbicas e Hidrofílicas , Peptídeos
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