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1.
Int J Mol Sci ; 22(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34360829

RESUMO

Pancreatic cancer (PC), one of the most lethal solid tumors in humans, has a five-year survival rate of only 4%. Surgical treatment is the only accepted therapy with curative intent because the vast majority of these tumors are chemoresistant. Unfortunately, due to the aggressive nature of these tumors, fewer than 20% are resectable when the first symptoms occur. Novel therapies are required to overcome all these therapeutic issues, and the development of active nanocarriers represents an exciting opportunity to improve PC outcomes. The present review focuses on recent advances in the field of nanotechnology with application in PC treatment.


Assuntos
Nanopartículas/uso terapêutico , Nanotecnologia/métodos , Neoplasias Pancreáticas , Animais , Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/tratamento farmacológico
2.
Int J Mol Sci ; 22(15)2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34360621

RESUMO

Metabolic syndrome (MetS) is a set of complex, chronic inflammatory conditions that are characterized by central obesity and associated with an increased risk of cardiovascular diseases. In recent years, microRNAs (miRNAs) have become an important type of endocrine factors, which play crucial roles in maintaining energy balance and metabolic homeostasis. However, its unfavorable properties such as easy degradation in blood and off-target effect are still a barrier for clinical application. Nanosystem based delivery possess strong protection, high bioavailability and control release rate, which is beneficial for success of gene therapy. This review first describes the current progress and advances on miRNAs associated with MetS, then provides a summary of the therapeutic potential and targets of miRNAs in metabolic organs. Next, it discusses recent advances in the functionalized development of classic delivery systems (exosomes, liposomes and polymers), including their structures, properties, functions and applications. Furthermore, this work briefly discusses the intelligent strategies used in emerging novel delivery systems (selenium nanoparticles, DNA origami, microneedles and magnetosomes). Finally, challenges and future directions in this field are discussed provide a comprehensive overview of the future development of targeted miRNAs delivery for MetS treatment. With these contributions, it is expected to address and accelerate the development of effective NA delivery systems for the treatment of MetS.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Terapia Genética/métodos , Síndrome Metabólica/terapia , MicroRNAs/uso terapêutico , Nanoestruturas , Sistemas de Liberação de Medicamentos/tendências , Exossomos , Humanos , Lipossomos
3.
Int J Mol Sci ; 22(16)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34445799

RESUMO

Concerns associated with nanocarriers' therapeutic efficacy and side effects have led to the development of strategies to advance them into targeted and responsive delivery systems. Owing to their bioactivity and biocompatibility, peptides play a key role in these strategies and, thus, have been extensively studied in nanomedicine. Peptide-based nanocarriers, in particular, have burgeoned with advances in purely peptidic structures and in combinations of peptides, both native and modified, with polymers, lipids, and inorganic nanoparticles. In this review, we summarize advances on peptides promoting gene delivery systems. The efficacy of nucleic acid therapies largely depends on cell internalization and the delivery to subcellular organelles. Hence, the review focuses on nanocarriers where peptides are pivotal in ferrying nucleic acids to their site of action, with a special emphasis on peptides that assist anionic, water-soluble nucleic acids in crossing the membrane barriers they encounter on their way to efficient function. In a second part, we address how peptides advance nanoassembly delivery tools, such that they navigate delivery barriers and release their nucleic acid cargo at specific sites in a controlled fashion.


Assuntos
Portadores de Fármacos/química , Ácidos Nucleicos/química , Ácidos Nucleicos Peptídicos/química , Peptídeos/química , Animais , Sistemas de Liberação de Medicamentos/métodos , Humanos , Nanomedicina/métodos , Nanopartículas/química
4.
Theranostics ; 11(16): 7896-7910, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335971

RESUMO

Rationale: Small-molecule prodrug nanoassembly is emerging as an efficient platform for chemotherapy. The self-assembly stability plays a vital role on the drug delivery efficiency of prodrug nanoassembly. It is reported that fluoroalkylation could improve the self-assembly stability of amphiphilic polymers by utilizing the unique fluorination effect. But the application of fluoroalkylation on small-molecule prodrug nanoassembly has never been reported. Methods: Here, fluoro-modified prodrug was developed by conjugating paclitaxel with perfluorooctanol (F8-SS-PTX), and the paclitaxel-octanol prodrug (C8-SS-PTX) was used as control. The fluoro-mediated self-assembly mechanisms were illustrated using molecular dynamics simulation. In addition, the impacts of fluoroalkylation on the pharmacy characters, in vivo fate and antitumor effect of small-molecule prodrug nanoassembly were investigated in details. Results: Fluoroalkylation significantly improved the self-assembly stability of F8-SS-PTX NPs both in vitro and in vivo, which could be attributed to the fluoro-mediated hydrophobic force and halogen bonds. The AUC0-24h and tumor accumulation of F8-SS-PTX NPs was 6-fold and 2-fold higher than that of C8-SS-PTX NPs, respectively. As a result, F8-SS-PTX NPs exhibited much better antitumor effect than C8-SS-PTX NPs and Abraxane. Conclusion: Fluoroalkylation could improve the self-assembly stability, in vivo fate, and antitumor efficacy of small-molecule prodrug nanoassemblies, which could be an effective strategy for the rational design of advanced nanomedicines.


Assuntos
Fluoretos/química , Pró-Fármacos/química , Nanomedicina Teranóstica/métodos , Animais , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos/fisiologia , Fluoretação/métodos , Humanos , Camundongos , Simulação de Dinâmica Molecular , Nanomedicina/métodos , Nanopartículas/química , Paclitaxel/uso terapêutico , Polietilenoglicóis/química , Polímeros/química , Pró-Fármacos/farmacologia
5.
Theranostics ; 11(16): 8043-8056, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335979

RESUMO

Rationale: As a potentially life-threatening disorder, cerebral ischemia-reperfusion (I/R) injury is associated with significantly high mortality, especially the irreversible brain tissue damage associated with increased reactive oxygen radical production and excessive inflammation. Currently, the insufficiency of targeted drug delivery and "on-demand" drug release remain the greatest challenges for cerebral I/R injury therapy. Bioengineered cell membrane-based nanotherapeutics mimic and enhance natural membrane functions and represent a potentially promising approach, relying on selective interactions between receptors and chemokines and increase nanomedicine delivery efficiency into the target tissues. Methods: We employed a systematic method to synthesize biomimetic smart nanoparticles. The CXCR4-overexpressing primary mouse thoracic aorta endothelial cell (PMTAEC) membranes and RAPA@HOP were extruded through a 200 nm polycarbonate porous membrane using a mini-extruder to harvest the RAPA@BMHOP. The bioengineered CXCR4-overexpressing cell membrane-functionalized ROS-responsive nanotherapeutics, loaded with rapamycin (RAPA), were fabricated to enhance the targeted delivery to lesions with pathological overexpression of SDF-1. Results: RAPA@BMHOP exhibited a three-fold higher rate of target delivery efficacy via the CXCR4/SDF-1 axis than its non-targeting counterpart in an in vivo model. Additionally, in response to the excessive pathological ROS, nanotherapeutics could be degraded to promote "on-demand" cargo release and balance the ROS level by p-hydroxy-benzyl alcohol degradation, thereby scavenging excessive ROS and suppressing the free radical-induced focal damage and local inflammation. Also, the stealth effect of cell membrane coating functionalization on the surface resulted in extended circulation time and high stability of nanoparticles. Conclusion: The biomimetic smart nanotherapeutics with active targeting, developed in this study, significantly improved the therapeutic efficacy and biosafety profiles. Thus, these nanoparticles could be a candidate for efficient therapy of cerebral I/R injury.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Receptores CXCR4/metabolismo , Traumatismo por Reperfusão/terapia , Animais , Bioengenharia/métodos , Materiais Biomiméticos/farmacologia , Isquemia Encefálica/metabolismo , Membrana Celular/metabolismo , Liberação Controlada de Fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nanomedicina/métodos , Nanopartículas/administração & dosagem , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/metabolismo , Receptores CXCR4/genética , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais/fisiologia
6.
Theranostics ; 11(16): 7869-7878, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335969

RESUMO

Goals: Chemotherapy, the most conventional modality for cancer therapy, usually brings serious side effects because of the low cancer-therapeutic specificity and bioavailability. It is of great significance for cancer treatment to develop new effective strategies to regulate biochemical reactions in organelles, enhance the specificity of chemotherapeutic drugs and reduce their side effects. Methods: We report herein a zeolitic imidazole framework-90 (ZIF-90) based nanoplatform, which was used to initiate a series of mitochondrial cascade reactions using ATP as a molecular switch for cancer therapy. The thioketal linked camptothecin (camptothecin prodrug, TK-CPT) and 2-Methoxyestradiol (2-ME) were encapsulated into the pores of ZIF-90 nanoparticles using a simple one-pot method, and the nanoplatform was finally coated with a layer of homologous cell membrane. Results: Mitochondrial ATP can efficiently degrade ZIF-90 and then release the loaded 2-ME and CPT prodrugs. 2-ME can inhibit the activity of superoxide dismutase (SOD), which induces the up-regulation of reactive oxygen species (ROS) in situ. The thioketal linkers in CPT prodrug can respond to ROS, thereby achieving subsequent release of parent CPT drug. This cascade of reactions can lead to prolonged high oxidative stress and cause continuous cancer cell apoptosis, due to the increased ROS level and the liberation of CPT. Conclusion: We constructed an ATP-triggered strategy using nanoscale ZIF-90 to initiate mitochondrial cascade reactions for cancer therapy. The ZIF-90 based nanoplatform exhibited low cytotoxicity, good mitochondria-targeting ability, and excellent therapeutic effect. In vivo experiments demonstrated that the growth of tumor can be efficiently inhibited in a mouse model. This ATP-triggered strategy to induce mitochondrial biochemical reactions offers more possibilities for developing organelle-targeted therapeutic platforms.


Assuntos
Antineoplásicos/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Zeolitas/química , Trifosfato de Adenosina/química , Trifosfato de Adenosina/metabolismo , Animais , Antineoplásicos/farmacologia , Disponibilidade Biológica , Linhagem Celular Tumoral , China , Liberação Controlada de Fármacos/fisiologia , Imidazóis/química , Imidazóis/metabolismo , Imidazóis/farmacologia , Camundongos , Mitocôndrias/metabolismo , Nanopartículas/administração & dosagem , Neoplasias/metabolismo , Pró-Fármacos/química , Espécies Reativas de Oxigênio/metabolismo , Zeolitas/metabolismo , Zeolitas/farmacologia
7.
Int J Mol Sci ; 22(14)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34299020

RESUMO

Supramolecular hydrogels are 3D, elastic, water-swelled materials that are held together by reversible, non-covalent interactions, such as hydrogen bonds, hydrophobic, ionic, host-guest interactions, and metal-ligand coordination. These interactions determine the hydrogels' unique properties: mechanical strength; stretchability; injectability; ability to self-heal; shear-thinning; and sensitivity to stimuli, e.g., pH, temperature, the presence of ions, and other chemical substances. For this reason, supramolecular hydrogels have attracted considerable attention as carriers for active substance delivery systems. In this paper, we focused on the various types of non-covalent interactions. The hydrogen bonds, hydrophobic, ionic, coordination, and host-guest interactions between hydrogel components have been described. We also provided an overview of the recent studies on supramolecular hydrogel applications, such as cancer therapy, anti-inflammatory gels, antimicrobial activity, controlled gene drug delivery, and tissue engineering.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Hidrogéis/química , Polímeros/química , Engenharia Tecidual/métodos , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Materiais Biocompatíveis/química , Preparações de Ação Retardada/química , Técnicas de Transferência de Genes , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Íons/química , Ligantes , Temperatura
8.
Molecules ; 26(14)2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34299416

RESUMO

In the past decades, nanosized drug delivery systems (DDS) have been extensively developed and studied as a promising way to improve the performance of a drug and reduce its undesirable side effects. DDSs are usually very complex supramolecular assemblies made of a core that contains the active substance(s) and ensures a controlled release, which is surrounded by a corona that stabilizes the particles and ensures the delivery to the targeted cells. To optimize the design of engineered DDSs, it is essential to gain a comprehensive understanding of these core-shell assemblies at the atomic level. In this review, we illustrate how solid-state nuclear magnetic resonance (ssNMR) spectroscopy has become an essential tool in DDS design.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Ressonância Magnética Nuclear Biomolecular/métodos , Polímeros/química
9.
Molecules ; 26(14)2021 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-34299485

RESUMO

Oxyresveratrol has recently attracted much research attention due to its simple chemical structure and diverse therapeutic potentials. Previous reviews describe the chemistry and biological activities of this phytoalexin, but additional coverage and greater accessibility are still needed. The current review provides a more comprehensive summary, covering research from 1955 to the present year. Oxyresveratrol occurs in both gymnosperms and angiosperms. However, it has never been reported in plants in the subclass Sympetalae, and this point might be of both chemotaxonomic and biosynthetic importance. Oxyresveratrol can be easily obtained from plant materials by conventional methods, and several systems for both qualitative and quantitative analysis of oxyresveratrol contents in plant materials and plant products are available. Oxyresveratrol possesses diverse biological and pharmacological activities such as the inhibition of tyrosinase and melanogenesis, antioxidant and anti-inflammatory activities, and protective effects against neurological disorders and digestive ailments. However, the unfavorable pharmacokinetic properties of oxyresveratrol, including low water solubility and poor oral availability and stability, have posed challenges to its development as a useful therapeutic agent. Recently, several delivery systems have emerged, with promising outcomes that may improve chances for the clinical study of oxyresveratrol.


Assuntos
Extratos Vegetais/farmacologia , Extratos Vegetais/farmacocinética , Estilbenos/farmacologia , Estilbenos/farmacocinética , Animais , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Humanos , Monofenol Mono-Oxigenase/metabolismo
10.
Molecules ; 26(14)2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34299547

RESUMO

The aspect of drug delivery is significant in many biomedical subareas including tissue engineering. Many studies are being performed to develop composites with application potential for bone tissue regeneration which at the same provide adequate conditions for osteointegration and deliver the active substance conducive to the healing process. Hydroxyapatite shows a great potential in this field due to its osteoinductive and osteoconductive properties. In the paper, hydroxyapatite synthesis via the wet precipitation method and its further use as a ceramic phase of polymer-ceramic composites based on PVP/PVA have been presented. Firstly, the sedimentation rate of hydroxyapatite in PVP solutions has been determined, which allowed us to select a 15% PVP solution (sedimentation rate was 0.0292 mm/min) as adequate for preparation of homogenous reaction mixture treated subsequently with UV radiation. Both FT-IR spectroscopy and EDS analysis allowed us to confirm the presence of both polymer and ceramic phase in composites. Materials containing hydroxyapatite showed corrugated and well-developed surface. Composites exhibited swelling properties (hydroxyapatite reduced this property by 25%) in simulated physiological fluids, which make them useful in drug delivery (swelling proceeds parallel to the drug release). The short synthesis time, possibility of preparation of composites with desired shapes and sizes and determined physicochemical properties make the composites very promising for biomedical purposes.


Assuntos
Cerâmica/química , Durapatita/química , Polímeros/química , Álcool de Polivinil/química , Polivinil/química , Pirrolidinas/química , Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Humanos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Engenharia Tecidual/métodos
11.
Adv Drug Deliv Rev ; 176: 113867, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34280513

RESUMO

Prophylactic vaccines have evolved from traditional whole-cell vaccines to safer subunit vaccines. However, subunit vaccines still face problems, such as poor immunogenicity and low efficiency, while traditional adjuvants are usually unable to meet specific response needs. Advanced delivery vectors are important to overcome these barriers; they have favorable safety and effectiveness, tunable properties, precise location, and immunomodulatory capabilities. Nevertheless, there has been no systematic summary of the delivery systems to cover a wide range of infectious pathogens. We herein summarized and compared the delivery systems for major or epidemic infectious diseases caused by bacteria, viruses, fungi, and parasites. We also included the newly licensed vaccines (e.g., COVID-19 vaccines) and those close to licensure. Furthermore, we highlighted advanced delivery systems with high efficiency, cross-protection, or long-term protection against epidemic pathogens, and we put forward prospects and thoughts on the development of future prophylactic vaccines.


Assuntos
Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , Doenças Transmissíveis/terapia , Sistemas de Liberação de Medicamentos/métodos , Profilaxia Pré-Exposição/métodos , Animais , COVID-19/epidemiologia , COVID-19/imunologia , Vacinas contra COVID-19/imunologia , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/imunologia , Epidemias/prevenção & controle , Humanos , Lipossomos , Nanopartículas/administração & dosagem
12.
Molecules ; 26(14)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34299461

RESUMO

Hierarchically porous materials, such as wrinkled mesoporous silica (WMS), have gained interest in the last couple of decades, because of their wide range of applications in fields such as nanomedicine, energy, and catalysis. The mechanism of formation of these nanostructures is not fully understood, despite various groups reporting very comprehensive studies. Furthermore, achieving particle diameters of 100 nm or less has proven difficult. In this study, the effects on particle size, pore size, and particle morphology of several co-solvents were evaluated. Additionally, varying concentrations of acid during synthesis affected the particle sizes, yielding particles smaller than 100 nm. The morphology and physical properties of the nanoparticles were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and dynamic light scattering (DLS). Homogeneous and spherical WMS, with the desired radial wrinkle morphology and particle sizes smaller than 100 nm, were obtained. The effect of the nature of the co-solvents and the concentration of acid are explained within the frame of previously reported mechanisms of formation, to further elucidate this intricate process.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Nanopartículas Metálicas/química , Dióxido de Silício/química , Adsorção , Portadores de Fármacos/química , Microscopia Eletrônica de Varredura/métodos , Microscopia Eletrônica de Transmissão/métodos , Nanopartículas/química , Nanoestruturas/química , Tamanho da Partícula , Porosidade , Solventes/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Difração de Raios X/métodos
13.
Nature ; 596(7871): 291-295, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34321659

RESUMO

So far, gene therapies have relied on complex constructs that cannot be finely controlled1,2. Here we report a universal switch element that enables precise control of gene replacement or gene editing after exposure to a small molecule. The small-molecule inducers are currently in human use, are orally bioavailable when given to animals or humans and can reach both peripheral tissues and the brain. Moreover, the switch system, which we denote Xon, does not require the co-expression of any regulatory proteins. Using Xon, the translation of the desired elements for controlled gene replacement or gene editing machinery occurs after a single oral dose of the inducer, and the robustness of expression can be controlled by the drug dose, protein stability and redosing. The ability of Xon to provide temporal control of protein expression can be adapted for cell-biology applications and animal studies. Additionally, owing to the oral bioavailability and safety of the drugs used, the Xon switch system provides an unprecedented opportunity to refine and tailor the application of gene therapies in humans.


Assuntos
Processamento Alternativo/efeitos dos fármacos , Edição de Genes/métodos , Terapia Genética/métodos , Biossíntese de Proteínas/efeitos dos fármacos , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Proteína 9 Associada à CRISPR/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Eritropoetina/biossíntese , Eritropoetina/genética , Eritropoetina/metabolismo , Éxons/genética , Feminino , Demência Frontotemporal/metabolismo , Células HEK293 , Humanos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Atrofia Muscular Espinal/metabolismo , Lipofuscinoses Ceroides Neuronais/metabolismo , Progranulinas/biossíntese , Progranulinas/genética , Proteína 1 de Sobrevivência do Neurônio Motor/metabolismo , Proteína 2 de Sobrevivência do Neurônio Motor/metabolismo
14.
Molecules ; 26(13)2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34279392

RESUMO

Precision medicine is based on innovative administration methods of active principles. Drug delivery on tissue of interest allows improving the therapeutic index and reducing the side effects. Active targeting by means of drug-encapsulated micelles decorated with targeting bioactive moieties represents a new frontier. Between the bioactive moieties, peptides, for their versatility, easy synthesis and immunogenicity, can be selected to direct a drug toward a considerable number of molecular targets overexpressed on both cancer vasculature and cancer cells. Moreover, short peptide sequences can facilitate cellular intake. This review focuses on micelles achieved by self-assembling or mixing peptide-grafted surfactants or peptide-decorated amphiphilic copolymers. Nanovectors loaded with hydrophobic or hydrophilic cytotoxic drugs or with gene silence sequences and externally functionalized with natural or synthetic peptides are described based on their formulation and in vitro and in vivo behaviors.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Micelas , Nanomedicina/métodos , Peptídeos/química , Medicina de Precisão/métodos , Animais , Humanos , Peptídeos/efeitos adversos
15.
Molecules ; 26(11)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200350

RESUMO

A considerable interest in cancer research is represented by the development of magnetic nanoparticles based on biofunctionalized polymers for controlled-release systems of hydrophobic chemotherapeutic drugs targeted only to the tumor sites, without affecting normal cells. The objective of the paper is to present the synthesis and in vitro evaluation of the nanocomposites that include a magnetic core able to direct the systems to the target, a polymeric surface shell that provides stabilization and multi-functionality, a chemotherapeutic agent, Paclitaxel (PTX), and a biotin tumor recognition layer. To our best knowledge, there are no studies concerning development of magnetic nanoparticles obtained by partial oxidation, based on biotinylated N-palmitoyl chitosan loaded with PTX. The structure, external morphology, size distribution, colloidal and magnetic properties analyses confirmed the formation of well-defined crystalline magnetite conjugates, with broad distribution, relatively high saturation magnetization and irregular shape. Even if the ability of the nanoparticles to release the drug in 72 h was demonstrated, further complex in vitro and in vivo studies will be performed in order to validate the magnetic nanoparticles as PTX delivery system.


Assuntos
Antineoplásicos Fitogênicos/química , Biotina/química , Quitosana/análogos & derivados , Nanopartículas de Magnetita/química , Paclitaxel/química , Linhagem Celular Tumoral , Quitosana/química , Coloides/química , Preparações de Ação Retardada/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Humanos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Células MCF-7 , Polímeros/química
16.
Molecules ; 26(12)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200716

RESUMO

In this study, we report pH-responsive metal-based biopolymer nanoparticles (NPs) for tumor-specific chemotherapy. Here, aminated hyaluronic acid (aHA) coupled with 2,3-dimethylmaleic anhydride (DMA, as a pH-responsive moiety) (aHA-DMA) was electrostatically complexed with ferrous chloride tetrahydrate (FeCl2/4H2O, as a chelating metal) and doxorubicin (DOX, as an antitumor drug model), producing DOX-loaded Fe-based hyaluronate nanoparticles (DOX@aHA-DMA/Fe NPs). Importantly, the DOX@aHA-DMA/Fe NPs improved tumor cellular uptake due to HA-mediated endocytosis for tumor cells overexpressing CD44 receptors. As a result, the average fluorescent DOX intensity observed in MDA-MB-231 cells (with CD44 receptors) was ~7.9 × 102 (DOX@HA/Fe NPs, without DMA), ~8.1 × 102 (DOX@aHA-DMA0.36/Fe NPs), and ~9.3 × 102 (DOX@aHA-DMA0.60/Fe NPs). Furthermore, the DOX@aHA-DMA/Fe NPs were destabilized due to ionic repulsion between Fe2+ and DMA-detached aHA (i.e., positively charged free aHA) in the acidic environment of tumor cells. This event accelerated the release of DOX from the destabilized NPs. Our results suggest that these NPs can be promising tumor-targeting drug carriers responding to acidic endosomal pH.


Assuntos
Doxorrubicina/química , Endossomos/química , Compostos Ferrosos/química , Ácido Hialurônico/química , Nanopartículas/química , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Endocitose/efeitos dos fármacos , Feminino , Humanos , Receptores de Hialuronatos/metabolismo , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Endogâmicos BALB C
17.
Molecules ; 26(12)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200887

RESUMO

Royal jelly is a natural substance produced by worker bees that possesses a variety of biological activities, including antioxidant, anti-inflammatory, antibacterial, and protective. Although fresh royal jelly is kept at low temperatures, to increase its stability, it needs to be incorporated into pharmaceutical formulations, such as in situ gels. The aim of this study was to formulate in situ ocular gels containing Lithuanian royal jelly for topical corneal use in order to increase the retention time of the formulation on the ocular surface and bioavailability. Gels were evaluated for physicochemical characteristics (pH, rheological properties, refractive index) and in vitro drug release measuring the amount of 10-hydroxy-2-decenoic acid (10-HDA). An ocular irritation test and cell viability tests were performed using the SIRC (Statens Seruminstitut Rabbit Cornea) cell culture line. Results indicated that all the in situ gels were within an acceptable pH and refractive index range close to corneal properties. Rheology studies have shown that the gelation temperature varies between 25 and 32 °C, depending on the amount of poloxamers. The release studies have shown that the release of 10-HDA from in situ gels is more sustained than royal jelly suspension. All gel formulations were non-irritant according to the short-time exposure test (STE) using the SIRC cell culture line, and long-term cell viability studies indicated that the formulations used in small concentrations did not induce cell death. Prepared in situ gels containing royal jelly have potential for ocular drug delivery, and they may improve the bioavailability, stability of royal jelly, and formation of non-irritant ocular formulations.


Assuntos
Córnea/efeitos dos fármacos , Ácidos Graxos/química , Ácidos Graxos/farmacologia , Géis/química , Géis/farmacologia , Animais , Abelhas/metabolismo , Disponibilidade Biológica , Produtos Biológicos/química , Produtos Biológicos/farmacocinética , Produtos Biológicos/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Química Farmacêutica/métodos , Córnea/metabolismo , Ácidos Decanoicos/química , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos/efeitos dos fármacos , Excipientes/química , Géis/farmacocinética , Poloxâmero/química , Coelhos , Reologia , Temperatura
18.
Molecules ; 26(12)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200947

RESUMO

The use of nanosized particles has emerged to facilitate selective applications in medicine. Drug-delivery systems represent novel opportunities to provide stricter, focused, and fine-tuned therapy, enhancing the therapeutic efficacy of chemical agents at the molecular level while reducing their toxic effects. Melatonin (N-acetyl-5-methoxytriptamine) is a small indoleamine secreted essentially by the pineal gland during darkness, but also produced by most cells in a non-circadian manner from which it is not released into the blood. Although the therapeutic promise of melatonin is indisputable, aspects regarding optimal dosage, biotransformation and metabolism, route and time of administration, and targeted therapy remain to be examined for proper treatment results. Recently, prolonged release of melatonin has shown greater efficacy and safety when combined with a nanostructured formulation. This review summarizes the role of melatonin incorporated into different nanocarriers (e.g., lipid-based vesicles, polymeric vesicles, non-ionic surfactant-based vesicles, charge carriers in graphene, electro spun nanofibers, silica-based carriers, metallic and non-metallic nanocomposites) as drug delivery system platforms or multilevel determinations in various in vivo and in vitro experimental conditions. Melatonin incorporated into nanosized materials exhibits superior effectiveness in multiple diseases and pathological processes than does free melatonin; thus, such information has functional significance for clinical intervention.


Assuntos
Portadores de Fármacos/química , Melatonina/química , Melatonina/farmacologia , Nanopartículas/química , Animais , Ritmo Circadiano/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Humanos , Nanoestruturas/química , Glândula Pineal/efeitos dos fármacos
19.
Molecules ; 26(12)2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34204668

RESUMO

Pluronic polymers (pluronics) are a unique class of synthetic triblock copolymers containing hydrophobic polypropylene oxide (PPO) and hydrophilic polyethylene oxide (PEO) arranged in the PEO-PPO-PEO manner. Due to their excellent biocompatibility and amphiphilic properties, pluronics are an ideal and promising biological material, which is widely used in drug delivery, disease diagnosis, and treatment, among other applications. Through self-assembly or in combination with other materials, pluronics can form nano carriers with different morphologies, representing a kind of multifunctional pharmaceutical excipients. In recent years, the utilization of pluronic-based multi-functional drug carriers in tumor treatment has become widespread, and various responsive drug carriers are designed according to the characteristics of the tumor microenvironment, resulting in major progress in tumor therapy. This review introduces the specific role of pluronic-based polymer drug delivery systems in tumor therapy, focusing on their physical and chemical properties as well as the design aspects of pluronic polymers. Finally, using newer literature reports, this review provides insights into the future potential and challenges posed by different pluronic-based polymer drug delivery systems in tumor therapy.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Propilenoglicóis/química , Propilenoglicóis/farmacologia , Portadores de Fármacos/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Neoplasias/tratamento farmacológico , Poloxâmero/química , Poloxâmero/metabolismo , Poloxâmero/farmacologia , Polietilenoglicóis/metabolismo , Polímeros/química , Polipropilenos/química , Polipropilenos/farmacologia , Propilenoglicóis/metabolismo , Microambiente Tumoral/efeitos dos fármacos
20.
Molecules ; 26(12)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208150

RESUMO

Protocatechuic aldehyde (PCAL) and protocatechuic acid (PCAC) are catechol derivatives and have broad therapeutic effects associated with their antiradical activity. Their pharmacological and physicochemical properties have been improved via the cyclodextrin (CD) encapsulation. Because the characteristics of ß-CD inclusion complexes with PCAL (1) and PCAC (2) are still equivocal, we get to the bottom of the inclusion complexation by an integrated study of single-crystal X-ray diffraction and DFT full-geometry optimization. X-ray analysis unveiled that PCAL and PCAC are nearly totally shielded in the ß-CD wall. Their aromatic rings are vertically aligned in the ß-CD cavity such that the functional groups on the opposite side of the ring (3,4-di(OH) and 1-CHO/1-COOH groups) are placed nearby the O6-H and O2-H/O3-H rims, respectively. The preferred inclusion modes in 1 and 2 help to establish crystal contacts of OH⋅⋅⋅O H-bonds with the adjacent ß-CD OH groups and water molecules. By contrast, the DFT-optimized structures of both complexes in the gas phase are thermodynamically stable via the four newly formed host-guest OH⋯O H-bonds. The intermolecular OH⋅⋅⋅O H-bonds between PCAL/PCAC 3,4-di(OH) and ß-CD O6-H groups, and the shielding of OH groups in the ß-CD wall help to stabilize these antioxidants in the ß-CD cavity, as observed in our earlier studies. Moreover, PCAL and PCAC in distinct lattice environments are compared for insights into their structural flexibility.


Assuntos
Antioxidantes/química , Benzaldeídos/química , Catecóis/química , Hidroxibenzoatos/química , beta-Ciclodextrinas/química , Antioxidantes/administração & dosagem , Benzaldeídos/administração & dosagem , Catecóis/administração & dosagem , Cristalografia por Raios X , Sistemas de Liberação de Medicamentos/métodos , Ligação de Hidrogênio , Hidroxibenzoatos/administração & dosagem , Termodinâmica , beta-Ciclodextrinas/administração & dosagem
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