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1.
Microb Pathog ; 191: 106679, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38718953

RESUMO

A crucial pathogenic mechanism in many bacterial diseases is the ability to create biofilms. Biofilms are suspected to play a role in over 80 % of microbial illnesses in humans. In light of the critical requirement for efficient management of bacterial infections, researchers have explored alternative techniques for treating bacterial disorders. One of the most promising ways to address this issue is through the development of long-lasting coatings with antibacterial properties. In recent years, antibacterial treatments based on metallic nanoparticles (NPs) have emerged as an effective strategy in the fight over bacterial drug resistance. Zinc oxide nanoparticles (ZnO-NPs) are the basis of a new composite coating material. This article begins with a brief overview of the mechanisms that underlie bacterial resistance to antimicrobial drugs. A detailed examination of the properties of metallic nanoparticles (NPs) and their potential use as antibacterial drugs for curing drug-sensitive and resistant bacteria follows. Furthermore, we assess metal nanoparticles (NPs) as powerful agents to fight against antibiotic-resistant bacteria and the growth of biofilm, and we look into their potential toxicological effects for the development of future medicines.


Assuntos
Antibacterianos , Bactérias , Infecções Bacterianas , Biofilmes , Nanopartículas Metálicas , Óxido de Zinco , Biofilmes/efeitos dos fármacos , Óxido de Zinco/farmacologia , Óxido de Zinco/química , Antibacterianos/farmacologia , Nanopartículas Metálicas/química , Humanos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Bactérias/efeitos dos fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Biotecnologia
2.
Int J Biol Macromol ; 260(Pt 1): 129324, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38228210

RESUMO

In the rapidly evolving landscape of silver nanoparticles (Ag NPs) synthesis, the focus has predominantly been on plant-derived sources, leaving the realm of biological or animal origins relatively uncharted. Breaking new ground, our study introduces a pioneering approach: the creation of Ag NPs using marine fish collagen, termed ClAg NPs, and offers a comprehensive exploration of their diverse attributes. To begin, we meticulously characterized ClAg NPs, revealing their spherical morphology, strong crystalline structure, and average diameter of 5 to 100 nm. These NPs showed potent antibacterial activity, notably against S. aureus (gram-positive), surpassing their efficacy against S. typhi (gram-negative). Additionally, ClAg NPs effectively hindered the growth of MRSA biofilms at 500 µg/mL. Impressively, they demonstrated substantial antioxidant capabilities, out performing standard gallic acid. Although higher concentrations of ClAg NPs induced hemolysis (41.804 %), lower concentrations remained non hemolytic. Further evaluations delved into the safety and potential applications of ClAg NPs. In vitro cytotoxicity studies on HEK 293 and HeLa cells revealed dose-dependent toxicity, with IC50 of 75.28 µg/mL and 79.13 µg/mL, respectively. Furthermore, ClAg NPs affected seed germination, root, and shoot lengths in Mung plants, underscoring their relevance in agriculture. Lastly, zebrafish embryo toxicity assays revealed notable effects, particularly at 500 µg/mL, on embryo morphology and survival rates at 96 hpf. In conclusion, our study pioneers the synthesis and multifaceted evaluation of ClAg NPs, offering promise for their use as versatile nano therapeutics in the medical field and as high-value collagen-based nanobiomaterial with minimal environmental impact.


Assuntos
Nanopartículas Metálicas , Prata , Animais , Humanos , Prata/química , Nanopartículas Metálicas/química , Peixe-Zebra , Células HeLa , Staphylococcus aureus , Células HEK293 , Antibacterianos/farmacologia , Antibacterianos/química
3.
Curr Med Chem ; 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37828676

RESUMO

Microbial polyhydroxyalkanoates (PHAs) are bio-based aliphatic biopolyester produced by bacteria as an intracellular storage material of carbon and energy under stressed conditions. PHAs have been paid attention to due to their unique and impressive biological properties including high biodegradability, biocompatibility, low cytotoxicity, and different mechanical properties. Under this context, the development of drug-delivery nanosystems based on PHAs has been revealed to have numerous advantages compared with synthetic polymers that included biocompatibility, biodegradability, non-toxic, and low-cost production, among others. In this review article, we present the available state of the art of PHAs. Moreover, we discussed the potential benefits, weaknesses, and perspectives of PHAs to the develop drug delivery systems.

4.
Pharmaceutics ; 15(10)2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37896204

RESUMO

The skin is considered the largest and most accessible organ in the human body, and allows the use of noninvasive and efficient strategies for drug administration, such as the transdermal drug delivery system (TDDS). TDDSs are systems or patches, with the ability and purpose to deliver effective and therapeutic doses of drugs through the skin. Regarding the specific interaction between hydrogels (HG) and microneedles (MNs), we seek to find out how this combination would be applied in the context of drug delivery, and we detail some possible advantages of the methods used. Depending on the components belonging to the HG matrix, we can obtain some essential characteristics that make the combination of hydrogels-microneedles (HG-MNs) very advantageous, such as the response to external stimuli, among others. Based on multiple characteristics provided by HGMNs that are depicted in this work, it is possible to obtain unique properties that include controlled, sustained, and localized drug release, as well as the possibility of a synergistic association between the components of the formulation and the combination of more than one bioactive component. In conclusion, a system based on HG-MNs can offer many advantages in the biomedical field, bringing to light a new technological and safe system for improving the pharmacokinetics and pharmacodynamics of drugs and new treatment perspectives.

5.
Comput Biol Chem ; 106: 107932, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37487249

RESUMO

Lipopeptides are medicinally essential building blocks with strong hemolytic, antifungal and antibiotic potential. In the present research article, we are presenting our findings regarding the synthesis of N-alkylated lipopeptides via Ugi four-component approach, their antimicrobial potential against pathogenic (Gram-positive and Gram-negative) bacteria, as well as computational studies to investigate the compounds binding affinity and dynamic behavior with MurD antibacterial target. Molecular docking demonstrated the compounds have good binding ability with MurD enzyme. The FT94, FT95 and FT97 compounds revealed binding affinity scores of -8.585 kcal mol- 1, -7.660 kcal mol- 1 and -7.351 kcal mol- 1, respectively. Furthermore, dynamics analysis pointed the systems high structure dynamics. The docking and simulation results were validated by binding free energies, demonstrating solid intermolecular interactions and in the assay in vitro, the Minimal Inhibitory Concentration (MIC) of FT97 to Staphylococcus aureus (S. aureus) was 62.5 µg/mL. In conclusion, a moderate inhibitory response of peptoid FT97 was observed against the Gram-positive bacteria, S. aureus and B. cereus.


Assuntos
Anti-Infecciosos , Staphylococcus aureus , Simulação de Acoplamento Molecular , Antibacterianos/farmacologia , Lipopeptídeos/farmacologia
6.
Pharmaceutics ; 15(5)2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37242726

RESUMO

Slow-release delivery systems are needed to ensure long-term sustained treatments for retinal diseases such as age-related macular degeneration and diabetic retinopathy, which are currently treated with anti-angiogenic agents that require frequent intraocular injections. These can cause serious co-morbidities for the patients and are far from providing the adequate drug/protein release rates and required pharmacokinetics to sustain prolonged efficacy. This review focuses on the use of hydrogels, particularly on temperature-responsive hydrogels as delivery vehicles for the intravitreal injection of retinal therapies, their advantages and disadvantages for intraocular administration, and the current advances in their use to treat retinal diseases.

7.
Pharmaceutics ; 15(2)2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36839798

RESUMO

In light of the growing bacterial resistance to antibiotics and in the absence of the development of new antimicrobial agents, numerous antimicrobial delivery systems over the past decades have been developed with the aim to provide new alternatives to the antimicrobial treatment of infections. However, there are few studies that focus on the development of a rational design that is accurate based on a set of theoretical-computational methods that permit the prediction and the understanding of hydrogels regarding their interaction with cationic antimicrobial peptides (cAMPs) as potential sustained and localized delivery nanoplatforms of cAMP. To this aim, we employed docking and Molecular Dynamics simulations (MDs) that allowed us to propose a rational selection of hydrogel candidates based on the propensity to form intermolecular interactions with two types of cAMPs (MP-L and NCP-3a). For the design of the hydrogels, specific building blocks were considered, named monomers (MN), co-monomers (CM), and cross-linkers (CL). These building blocks were ranked by considering the interaction with two peptides (MP-L and NCP-3a) as receptors. The better proposed hydrogel candidates were composed of MN3-CM7-CL1 and MN4-CM5-CL1 termed HG1 and HG2, respectively. The results obtained by MDs show that the biggest differences between the hydrogels are in the CM, where HG2 has two carboxylic acids that allow the forming of greater amounts of hydrogen bonds (HBs) and salt bridges (SBs) with both cAMPs. Therefore, using theoretical-computational methods allowed for the obtaining of the best virtual hydrogel candidates according to affinity with the specific cAMP. In conclusion, this study showed that HG2 is the better candidate for future in vitro or in vivo experiments due to its possible capacity as a depot system and its potential sustained and localized delivery system of cAMP.

8.
Int J Biol Macromol ; 233: 123514, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36739049

RESUMO

Nano-based drug delivery research is increasing due to the therapeutic applications for human health care. However, traditional chemical capping-based synthesis methods lead to unwanted toxicity effects. Hence, there is an urgent need for green synthesis-based and biocompatible synthesis methods. The current work describes for the first time the green synthesis of Moringa gum-capped MgO nanoparticles (Mgm-MgO NPs). Their antioxidant activity, hemolysis potential, cytotoxicity, phytotoxicity, toxicity by chorioallantoic membrane (CAM) chick embryo assay and in vivo toxicity in zebrafish embryos were described. The Mgm-MgO NPs exhibited significant antioxidant activity. The Mgm-MgO NPs at 500 µg/ml produced significant hemolysis (72.54 %), while lower concentrations did not. Besides, the cytotoxicity assessment of the Mgm-MgO NPs was conducted in PA-1 cells from human ovarian teratocarcinoma by MTT assay. The Mgm-MgO NPs (0.1-500 µg/ml) considerably reduced the viability of PA-1 cells. Furthermore, Mgm-MgO NPs had no significant effect on seed germination but had a significant effect on root and shoot length of mungbean (Vigna radiata). Additionally, the CAM assay was used to analyze the antiangiogenic potential of Mgm-MgO NPs, exhibiting no significant alterations after 72 h. Finally, the zebrafish embryotoxicity assay revealed that the Mgm-MgO NPs (0.1-500 µg/ml) did not affect morphology, mortality or survival rate.


Assuntos
Nanopartículas Metálicas , Moringa oleifera , Nanopartículas , Embrião de Galinha , Animais , Humanos , Óxido de Magnésio/farmacologia , Peixe-Zebra , Antioxidantes , Hemólise
9.
ACS Appl Mater Interfaces ; 15(8): 10398-10413, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36795046

RESUMO

The Kirsten rat sarcoma viral oncogene (KRAS) is one of the most well-known proto-oncogenes, frequently mutated in pancreatic and colorectal cancers, among others. We hypothesized that the intracellular delivery of anti-KRAS antibodies (KRAS-Ab) with biodegradable polymeric micelles (PM) would block the overactivation of the KRAS-associated cascades and revert the effect of its mutation. To this end, PM-containing KRAS-Ab (PM-KRAS) were obtained using Pluronic F127. The feasibility of using PM for antibody encapsulation as well as the conformational change of the polymer and its intermolecular interactions with the antibodies was studied, for the first time, using in silico modeling. In vitro, encapsulation of KRAS-Ab allowed their intracellular delivery in different pancreatic and colorectal cancer cell lines. Interestingly, PM-KRAS promoted a high proliferation impairment in regular cultures of KRAS-mutated HCT116 and MIA PaCa-2 cells, whereas the effect was neglectable in non-mutated or KRAS-independent HCT-8 and PANC-1 cancer cells, respectively. Additionally, PM-KRAS induced a remarkable inhibition of the colony formation ability in low-attachment conditions in KRAS-mutated cells. In vivo, when compared with the vehicle, the intravenous administration of PM-KRAS significantly reduced tumor volume growth in HCT116 subcutaneous tumor-bearing mice. Analysis of the KRAS-mediated cascade in cell cultures and tumor samples showed that the effect of PM-KRAS was mediated by a significant reduction of the ERK phosphorylation and a decrease in expression in the stemness-related genes. Altogether, these results unprecedently demonstrate that the delivery of KRAS-Ab mediated by PM can safely and effectively reduce the tumorigenicity and the stemness properties of KRAS-dependent cells, thus bringing up new possibilities to reach undruggable intracellular targets.


Assuntos
Neoplasias Colorretais , Neoplasias , Animais , Camundongos , Carcinogênese , Proliferação de Células , Neoplasias Colorretais/patologia , Micelas , Mutação , Polímeros/farmacologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/farmacologia , Espaço Intracelular
10.
Curr Med Chem ; 30(17): 1963-1970, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35770400

RESUMO

Bacteria and their enzymatic machinery, also called bacterial cell factories, produce a diverse variety of biopolymers, such as polynucleotides, polypeptides and polysaccharides, with different and fundamental cellular functions. Polysaccharides are the most widely used biopolymers, especially in biotechnology. This type of biopolymer, thanks to its physical and chemical properties, can be used to create a wide range of advanced bio-based materials, hybrid materials and nanocomposites for a variety of exciting biomedical applications. In contrast to synthetic polymers, bacterial polysaccharides have several advantages, such as biocompatibility, biodegradability, low immunogenicity, and non-toxicity, among others. On the other hand, the main advantage of bacterial polysaccharides compared to polymers extracted from other natural sources is that their physicochemical properties, such as purity, porosity, and malleability, among others, can be adapted to a specific application with the use of biotechnological tools and/or chemical modifications. Another great reason for using bacterial polysaccharides is due to the possibility of developing advanced materials from them using bacterial factories that can metabolize raw materials (recycling of industrial and agricultural wastes) that are readily available and in large quantities. Moreover, through this strategy, it is possible to curb environmental pollution. In this article, we project the desire to move towards large-scale production of bacterial polysaccharides taking into account the benefits, weaknesses and prospects in the near future for the development of advanced biological materials for medical and pharmaceutical purposes.


Assuntos
Nanocompostos , Polissacarídeos Bacterianos , Humanos , Biopolímeros/química , Polímeros , Biotecnologia
11.
Food Chem Toxicol ; 168: 113330, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35926645

RESUMO

In currently, biosynthesis of copper oxide nanoparticles (CuO NPs) are most widely used numerous in biological applications such as biosensor, energy, medicine, agriculture, environmental and industrial wastewater treatment. The hierarchical CuO NPs was synthesized via green chemistry method by using of Abutilon indicum (A. indicum) leaf extract, its nontoxic, facile and low-cost approaches. Biogenic synthesized CuO NPs was characterized by using a UV-visible absorption spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and Field mission scanning electron microscopy (FE-SEM) with Energy-dispersive X-ray spectroscopy (EDX) analysis. The synthesized CuO NPs was performed antibacterial activity against human pathogenic organisms of both Gram negative (Escherichia coli and Salmonella typhi) and Gram positive (Bacillus subtilis and Staphylococcus aureus) bacteria by using agar well diffusion method. Biological synthesized CuO NPs was showed potential bactericidal activity against Gram positive bacteria of B. subtilis than compared to Gram negative bacteria of E. coli. The cytotoxic effect of A. indicum mediated synthesized CuO NPs was evaluated against to human lung A549 and breast MDA-MB-231cancer cell lines by determined using of MTT assay. In furthermore, photocatalytic dye degradation was performed that synthesized CuO NPs have effectively removed 78% of malachite green dye molecule. Our investigation results suggested that the green synthesized CuO NPs potential biological activity of antibacterial activity against Gram positive bacterial, anticancer activity was effectively against MDA-MB-231cancer cell line and good dye degradation was exhibited in malachite green. The A. indicum aqueous leaf extract mediated synthesized CuO NPs has strongly suggested promising nano-biomaterials for fabrication of biomedical applications.


Assuntos
Neoplasias da Mama , Malvaceae , Nanopartículas Metálicas , Ágar/farmacologia , Antibacterianos/química , Neoplasias da Mama/tratamento farmacológico , Cobre/química , Cobre/farmacologia , Escherichia coli , Feminino , Bactérias Gram-Positivas , Humanos , Pulmão , Nanopartículas Metálicas/química , Testes de Sensibilidade Microbiana , Óxidos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Corantes de Rosanilina , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
12.
Carbohydr Polym ; 295: 119859, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-35988981

RESUMO

Local cancer treatment by in situ injections of thermo-responsive hydrogels (HG) offers several advantages over conventional systemic anti-cancer treatments. In this work, a biodegradable and multicompartmental HG composed of N-isopropylacrylamide, cellulose, citric acid, and ceric ammonium nitrate was developed for the controlled release of hydrophilic (doxorubicin) and hydrophobic (niclosamide) drugs. The formulation presented ideal properties regarding thermo-responsiveness, rheological behavior, drug release profile, biocompatibility, and biological activity in colon and ovarian cancer cells. Cellulose was found to retard drugs release rate, being only 4 % of doxorubicin and 30 % of niclosamide released after 1 week. This low release was sufficient to cause cell death in both cell lines. Moreover, HG demonstrated a proper injectability, in situ prevalence, and safety profile in vivo. Overall, the HG properties, together with its natural and eco-friendly composition, create a safe and efficient platform for the local treatment of non-resectable tumors or tumors requiring pre-surgical adjuvant therapy.


Assuntos
Hidrogéis , Neoplasias , Acrilamidas , Celulose/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacologia , Humanos , Hidrogéis/química , Niclosamida , Temperatura
13.
Materials (Basel) ; 15(14)2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35888365

RESUMO

The present study shows porous activated carbon obtained from Chenopodium quinoa Willd and Quillaja saponaria and their use as potential adsorbents to remove three types of dyes from aqueous solutions. The adsorption results were compared with commercial charcoal to check their efficiency. All porous carbon materials were activated using carbon dioxide and steam and fully characterized. Moreover, the steam-activated samples exhibited a high total pore volume with a BET surface area of around 800 m2 g−1. Batch adsorption experiments showed that commercial charcoal is the charcoal that offered the best adsorption efficiency for tartrazine and sunset yellow FCF. However, in the case of crystal violet, all activated carbons obtained from Chenopodium quinoa Willd and Quillaja saponaria showed the best captures, outperforming commercial charcoal. Molecular dockings of the dyes on the commercial charcoal surface were performed using AutoDock Vina. The kinetic results of the three isotherm's models for the present data follow the order: Langmuir~Freundlich > Temkin.

14.
Environ Res ; 213: 113655, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35716813

RESUMO

In the current scenario where more and more products containing nanomaterials are on the technological or pharmaceutical market, it is crucial to have a thorough knowledge of their toxicity before proposing possible applications. A proper analysis of the toxicity of the nanoproducts should include both in vitro and in vivo biological approaches and should consider that the synthesis and purification methods of nanomaterials may affect such toxicity. In the current work, the green synthesis of laminarin embedded ZnO nanoparticles (Lm-ZnO NPs) and their based chitosan capped ZnO nanocomposites (Ch-Lm-ZnO NCmps) is described for the first time. Furthermore, the evaluation of their in vitro cytotoxicity, phytotoxicity, and in vivo (Zebrafish embryo) toxicity was described. First, the green synthesized Lm-ZnO NPs and Ch-Lm-ZnO NCmps were fully physicochemically characterized. Lm-ZnO NPs were greatly agglomerated and had a spindle morphology ranging from 100 to 350 nm, while Ch-Lm-ZnO NCmps had irregular rod shape with flake-like structure clusters randomly aggregated with diverse sizes ranging from 20 to 250 nm. The in vitro cytotoxicity assessment of the green synthesized Lm-ZnO NPs and Ch-Lm-ZnO NCmps was carried out in normal human dermal fibroblasts (HDF) cells and human colon cancer (HT-29) cells by MTT assay. Lm-ZnO NPs and Ch-Lm-ZnO NCmps (0.1-500 µg/mL), significantly inhibited the viability of both cell lines, revealing dose-dependent cytotoxicity. Besides, the Lm-ZnO NPs and Ch-Lm-ZnO NCmps significantly affected seed germination and roots and shoots length of mung (Vigna radiata). Moreover, the zebrafish embryo toxicity of Lm-ZnO NPs and Ch-Lm-ZnO NCmps among the various concentrations used (0.1-500 µg/mL) caused deformities, increased mortality and decreased the survival rate of zebrafish embryo dose-dependently.


Assuntos
Quitosana , Nanopartículas Metálicas , Nanopartículas , Óxido de Zinco , Animais , Quitosana/química , Quitosana/toxicidade , Glucanos , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Nanopartículas/química , Peixe-Zebra , Óxido de Zinco/química , Óxido de Zinco/toxicidade
15.
Mater Sci Eng C Mater Biol Appl ; 131: 112483, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34857269

RESUMO

A rational design accurate based on the use of Statistical Design of the Experiments (DoE) and Molecular Dynamics Simulations Studies allows the prediction and the understanding of thermo-responsive hydrogels prepared regarding their gelation temperature and anti-cancer drug release rate. N-isopropylacrilamide (NIPAM) modified with specific co-monomers and crosslinkers, can be used to prepare "on-demand" thermo-responsive hydrogels with the ideal properties for clinical applications in which local sustained release of drugs is crucial. Two preferential formulations resulting from the predictive studies of DoE and In Silico methods were synthesized by radical polymerization, fully characterized, and loaded with the anticancer drug Doxorubicin (Dox). The hydrogel formulations were characterized by swelling rate, turbidity, FTIR, 1H NMR, SEM, gelation time, rheology, and biocompatibility assays. Both formulations demonstrated adequate morphologic, rheological, and biocompatibility properties; however, important differences in terms of drug retention were detected. As demonstrated by a Dox cumulative release study and posteriorly confirmed by an efficacy assay in an in vitro colorectal cancer model, the formulation composed by NIPAM and 4-penten-1-ol crosslinked with poly(ethylene glycol) diacrylate (PEGDA) (PNiPenPH) present a slow release over the time, presenting ideal properties to become and ideal depot system for the local sustained release of anticancer drugs as adjuvant therapy or in the case of non-resectable tumors.


Assuntos
Antineoplásicos , Neoplasias do Colo , Antineoplásicos/farmacologia , Neoplasias do Colo/tratamento farmacológico , Preparações de Ação Retardada , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Humanos , Hidrogéis , Temperatura
16.
Polymers (Basel) ; 13(22)2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34833292

RESUMO

Pesticides are used worldwide to increase crop yields in agriculture. However, their toxicity and accumulation capacity can make them toxic to the environment, animals and humans. In the case of workers chronically exposed to these substances, they must be sampled continuously, so urine is an excellent option. In this sense, this study proposes to use poly(vinyl alcohol)-malic acid hydrogels, and chitosan-coated calcium alginate as new sorbent phases to be used in pesticide determination processes in urine. To better understand the behavior of these materials in the capture and desorption process, molecular dynamics simulations (MDS) were used, and desorption experiments were performed, using mechanical agitation, ultrasound, and pH variation in the desorption process, in order to optimize the parameters to obtain better recoveries. Under the optimal experimental conditions, the maximum recoveries were of the order of 11% (CFN), 3% (KCF), 53% (DMT), 18% (MTD) and 35% (MTL). Although the recoveries were not exhaustive, they are a first approximation for the use of these new sorbent phases in the determination of this type of compound in aqueous solutions and urine.

17.
Int J Pharm ; 606: 120954, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34332061

RESUMO

Despite the enormous efforts done by the scientific community in the last decades, advanced cancer is still considered an incurable disease. New formulations are continuously under investigation to improve drugs therapeutic index, i.e., increase chemotherapeutic efficacy and reduce adverse effects. In this context, hydrogels-based systems for drug local sustained/controlled release have been proposed to reduce off-target effects caused by the repeated administration of systemic/oral anticancer drugs and improve their therapeutic effectiveness. Moreover, it increases the patient welfare by reducing the number of administrations needed. Among the several types of existing hydrogels, the thermo-responsive ones, which are able to change their physical state from liquid at 25 °C to a gel at the body temperature, i.e., 37 °C, gained special attention as in situ sustained drug release depot-systems in cancer treatment. To date, several thermo-responsive hydrogels have been used for drugs and/or genetic material delivery, yielding promising results both at preclinical and clinical evaluation stages. This culminates in the market authorization of Jelmyto® for the treatment of urothelial cancer. Here are summarized and discussed the last 10 years advances regarding the application of thermo-responsive hydrogels in local cancer treatment.


Assuntos
Hidrogéis , Neoplasias , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Humanos , Neoplasias/tratamento farmacológico , Temperatura
18.
Cancers (Basel) ; 13(5)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803133

RESUMO

Cancer remains as the second leading cause of death, worldwide. Despite the enormous important advances observed in the last decades, advanced stages of the disease remain incurable. The severe side effects associated to systemic high doses of chemotherapy and the development of drug resistance impairs a safe and efficiency anticancer therapy. Therefore, new formulations are continuously under research and development to improve anticancer drugs therapeutic index through localized delivery at tumor sites. Among a wide range of possibilities, hydrogels have recently gained special attention due to their potential to allow in situ sustained and controlled anticancer drug release. In particular, stimuli-responsive hydrogels which are able to change their physical state from liquid to gel accordingly to external factors such as temperature, pH, light, ionic strength, and magnetic field, among others. Some of these formulations presented promising results for the localized control and treatment of cancer. The present work aims to discuss the main properties and application of stimuli-responsive hydrogels in cancer treatment and summarize the most important advances observed in the last decades focusing on the use of pH-, light-, ionic strength-, and magnetic-responsive hydrogels.

19.
Curr Med Chem ; 28(30): 6274-6286, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33622222

RESUMO

BACKGROUND: Drug delivery systems such as hydrogels have become relevant in cardiovascular and metabolic therapies due to their sustained and controlled release properties of drugs, versatile polymer structures, safety, and biodegradability. RESULTS: The literature presented demonstrates that a hydrogel-based controlled release system increases the therapeutic efficacy in different components of the metabolic syndrome. Hypertension has been the most explored component with advances in in vitro and murine models. However, clinical evidence in humans is scarce, and more translational studies are needed. Hydrogel-based systems for diabetes, obesity, and dyslipidemia have been little explored. Observations mainly demonstrated an increase in therapeutic efficacy, in vitro and in vivo, for the use of insulin, leptin, and natural components, such as epigallocatechin gallate. In all cases, the hydrogel systems achieve better plasma levels of the loaded compound, higher bioavailability, and low cytotoxicity compared to conventional systems. Also, the evidence existing suggests that the development of an injectable hydrogel system for controlled release of drugs or therapeutic compounds is presented as an attractive option for MeS treatment, and due to the possibility of sustained pharmacological release, there is no need for repeated doses and a safe administration route. CONCLUSION: The following review aims to evaluate the use of the hydrogel systems in the therapy of diabetes, obesity, hypertension, and dyslipidemia, which are the main components of metabolic syndrome.


Assuntos
Hidrogéis , Síndrome Metabólica , Animais , Sistemas de Liberação de Medicamentos , Humanos , Síndrome Metabólica/tratamento farmacológico , Camundongos , Polímeros
20.
Pharmaceutics ; 12(10)2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33080791

RESUMO

A series of hydrogels with a specific release profile of linezolid was successfully synthesized. The hydrogels were synthesized by cross-linking polyvinyl alcohol (PVA) and aliphatic dicarboxylic acids, which include succinic acid (SA), glutaric acid (GA), and adipic acid (AA). The three crosslinked hydrogels were prepared by esterification and characterized by equilibrium swelling ratio, infrared spectroscopy, thermogravimetric analysis, mechanical properties, and scanning electron microscopy. The release kinetics studies of the linezolid from prepared hydrogels were investigated by cumulative drug release and quantified by chromatographic techniques. Mathematical models were carried out to understand the behavior of the linezolid release. These data revealed that the sustained release of linezolid depends on the aliphatic dicarboxylic acid chain length, their polarity, as well as the hydrogel crosslinking degree and mechanical properties. The in vitro antibacterial assay of hydrogel formulations was assessed in an Enterococcus faecium bacterial strain, showing a significant activity over time. The antibacterial results were consistent with cumulative release assays. Thus, these results demonstrated that the aliphatic dicarboxylic acids used as crosslinkers in the PVA hydrogels were a determining factor in the antibiotic release profile.

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