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1.
Mater Sci Eng C Mater Biol Appl ; 128: 112305, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474856

RESUMO

In spite of established evidence of the synergistic combination of hydrophobic anticancer molecule and microRNA for breast cancer treatment, their in vivo delivery has not been realized owing to their instability in the biological milieu and varied physicochemical properties. The present work reports folate targeted hybrid lipo-polymeric nanoplexes for co-delivering DTX and miR-34a. These nanoplexes exhibited a mean size of 129.3 nm with complexation efficiency at an 8:1 N/P ratio. The obtained nanoplexes demonstrated higher entrapment efficiency of DTX (94.8%) with a sustained release profile up to 85% till 48 h. Further, an improved transfection efficiency in MDA-MB-231 and 4T1 breast cancer cells was observed with uptake primarily through lipid-raft and clathrin-mediated endocytosis. Further, nanoplexes showed improved cytotoxicity (~3.5-5 folds), apoptosis (~1.6-2.0 folds), and change in expression of apoptotic genes (~4-7 folds) compared to the free treatment group in breast cancer cells. In vivo systemic administration of FA-functionalized DTX and FAM-siRNA-loaded nanoplexes showed an improved area under the curve (AUC) as well as circulation half-life compared to free DTX and naked FAM-labelled siRNA. Acute toxicity studies of the cationic polymer showed no toxicity at a dose equivalent to 10 mg/kg based on the hematological, biochemical, and histopathological examination.


Assuntos
Antineoplásicos , Neoplasias da Mama , MicroRNAs/administração & dosagem , Nanopartículas , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Docetaxel/farmacologia , Portadores de Fármacos/uso terapêutico , Feminino , Ácido Fólico , Humanos , MicroRNAs/genética , Polímeros/uso terapêutico
2.
Mater Sci Eng C Mater Biol Appl ; 128: 112324, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474875

RESUMO

Pulmonary drug delivery is governed by several biophysical parameters of delivery carriers, such as particle size, shape, density, charge, and surface modifications. Although much attention has been given to other parameters, particle shape effects have rarely been explored. In this work, we assess the influence of particle shape of inhaled delivery carriers on their aerodynamic properties and macrophage uptake by using polymeric microparticles of different geometries ranging in various sizes. Doxorubicin was conjugated to the polymer particles and the bioconjugates were characterized. Interestingly, the results of in-vitro lung deposition, performed using a next generation impactor, demonstrated a significant improvement in the aerodynamic properties of the rod-shaped particles with a high aspect ratio as compared to spherical particles with the same equivalent volume. The results of a macrophage uptake experiment demonstrate that the high aspect ratio particles were phagocytosed less than spherical particles. Furthermore, the cytotoxicity of these doxorubicin-conjugated particles was determined against murine macrophages, resulting in reduced toxicity when treated with high aspect ratio particles as compared to spherical particles. This project provides valuable insights into the influence of particle shape on aerodynamic properties and primary defense mechanisms in the peripheral lungs, while using polymeric microparticles of various sizes and geometries. Further systematic development can help translate these findings to preclinical and clinical studies for designing efficient inhalable delivery carriers.


Assuntos
Sistemas de Liberação de Medicamentos , Preparações Farmacêuticas , Administração por Inalação , Animais , Portadores de Fármacos , Pulmão , Camundongos , Tamanho da Partícula
3.
Mater Sci Eng C Mater Biol Appl ; 128: 112331, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474882

RESUMO

A totally biodegradable mixed system made up of phospholipids and zein was developed in order to effectively improve the photostability of all-trans retinoic acid (ATRA) preserving its pharmacological properties. Photon correlation spectroscopy showed that the formulation obtained using phospholipon 85G and zein at a ratio of 7:3 w/w was characterized by an average diameter of less than 200 nm, a narrow size distribution and a significant time- and temperature-dependent stability. The use of specific cryoprotectants such as mannose and glucose favoured the long-term storage of the nanocarriers after the freeze-drying procedure. The nanoparticles increased the stability of the ATRA against photochemical degradation with respect to the free drug and its antitumor effect was preserved as a consequence of the cell uptake of the colloidal systems. The results demonstrate the potential of the proposed hybrid nanosystems to provide a high level of stabilization for sensitive and labile antitumor compounds.


Assuntos
Nanopartículas , Zeína , Portadores de Fármacos , Tamanho da Partícula , Fosfolipídeos , Tretinoína/farmacologia
4.
Nanoscale ; 13(30): 13000-13013, 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34477783

RESUMO

Inorganic nanoparticles are gaining increasing attention as drug carriers because they respond to external physical stimuli, allowing therapy to be combined with diagnosis. Their drawback is low drug loading capacity, which can be improved by proper and efficacious functionalization. In this computational study, we take TiO2 spherical nanoparticles as prototype photoresponsive inorganic nanoparticles and we fully decorate them with two different types of bifunctional ligands: TETTs and DOPACs, which present different surface anchoring groups (silanol or catechol) but the same drug tethering COOH group, although in different concentrations (3 vs. 1), thus causing different steric hindrances. Then, we put these two types of nanocarriers in bulk water and in the presence of several DOX molecules and let the systems evolve through molecular dynamics (MD) simulations, clearly observing drug loading on the nanocarriers. This comparative MD study allows the investigation of the loading mechanism, performance of a conformational analysis and establishment of the guiding interactions through an energy decomposition analysis. We learn that DOX mostly interacts with the functionalized NPs through electrostatics, as a consequence of the protonated amino group, although several H-bonds are also established both with the ligands and with the oxide surface. Different ligands induce a different electrostatic potential around the NP; therefore, those which lead to the formation of more negative hotspots (here TETTs) are found to favour DOX binding. The leading role of electrostatics can provide a rational explanation for a pH-dependent drug release mechanism that is often invoked for DOX when reaching diseased cells because under anomalous acidic conditions both the NP surface and the carboxylate groups of the ligands are expected to get protonated, which of course would weaken, if not totally quench, the interaction of the nanocarrier with protonated DOX.


Assuntos
Doxorrubicina , Nanopartículas , Portadores de Fármacos , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Simulação de Dinâmica Molecular
5.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445466

RESUMO

To optimize the anti-tumor efficacy of combination therapy with paclitaxel (PTX) and imatinib (IMN), we used coaxial electrospray to prepare sequential-release core-shell microparticles composed of a PTX-loaded sodium hyaluronate outer layer and an IMN-loaded PLGA core. The morphology, size distribution, drug loading, differential scanning calorimetry (DSC), Fourier transform infrared spectra (FTIR), in vitro release, PLGA degradation, cellular growth inhibition, in vivo vaginal retention, anti-tumor efficacy, and local irritation in a murine orthotopic cervicovaginal tumor model after vaginal administration were characterized. The results show that such core-shell microparticles were of spherical appearance, with an average size of 14.65 µm and a significant drug-loading ratio (2.36% for PTX, 19.5% for IMN, w/w), which might benefit cytotoxicity against cervical-cancer-related TC-1 cells. The DSC curves indicate changes in the phase state of PTX and IMN after encapsulation in microparticles. The FTIR spectra show that drug and excipients are compatible with each other. The release profiles show sequential characteristics in that PTX was almost completely released in 1 h and IMN was continuously released for 7 days. These core-shell microparticles showed synergistic inhibition in the growth of TC-1 cells. Such microparticles exhibited prolonged intravaginal residence, a >90% tumor inhibitory rate, and minimal mucosal irritation after intravaginal administration. All results suggest that such microparticles potentially provide a non-invasive local chemotherapeutic delivery system for the treatment of cervical cancer by the sequential release of PTX and IMN.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Microesferas , Neoplasias do Colo do Útero/tratamento farmacológico , Animais , Apoptose , Proliferação de Células , Feminino , Humanos , Mesilato de Imatinib/administração & dosagem , Camundongos , Paclitaxel/administração & dosagem , Células Tumorais Cultivadas , Neoplasias do Colo do Útero/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445521

RESUMO

Poly(aspartamide) derivatives, one kind of amino acid-based polymers with excellent biocompatibility and biodegradability, meet the key requirements for application in various areas of biomedicine. Poly(aspartamide) derivatives with stimuli-responsiveness can usually respond to external stimuli to change their chemical or physical properties. Using external stimuli such as temperature and pH as switches, these smart poly(aspartamide) derivatives can be used for convenient drug loading and controlled release. Here, we review the synthesis strategies for preparing these stimuli-responsive poly(aspartamide) derivatives and the latest developments in their applications as drug carriers.


Assuntos
Ácido Aspártico/análogos & derivados , Portadores de Fármacos/síntese química , Polímeros/síntese química , Ácido Aspártico/síntese química , Ácido Aspártico/química , Preparações de Ação Retardada , Portadores de Fármacos/química , Concentração de Íons de Hidrogênio , Polímeros/química , Temperatura
7.
Molecules ; 26(15)2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34361825

RESUMO

Lipid-based nanocarriers (LNs) have made it possible to prolong corneal residence time and improve the ocular bioavailability of ophthalmic drugs. In order to investigate how the LNs interact with the ocular mucosa and reach the posterior eye segment, we have formulated lipid nanocarriers that were designed to bear a traceable fluorescent probe in the present work. The chosen fluorescent probe was obtained by a conjugation reaction between fluoresceinamine and the solid lipid excipient stearic acid, forming a chemically synthesized adduct (ODAF, N-(3',6'-dihydroxy-3-oxospiro [isobenzofuran-1(3H),9'-[9H] xanthen]-5-yl)-octadecanamide). The novel formulation (LN-ODAF) has been formulated and characterized in terms of its technological parameters (polydispersity index, mean particle size and zeta potential), while an in vivo study was carried out to assess the ability of LN-ODAF to diffuse through different ocular compartments. LN-ODAF were in nanometric range (112.7 nm ± 0.4), showing a good homogeneity and long-term stability. A TEM (transmission electron microscopy) study corroborated these results of characterization. In vivo results pointed out that after ocular instillation, LN ODAF were concentrated in the cornea (two hours), while at a longer time (from the second hour to the eighth hour), the fluorescent signals extended gradually towards the back of the eye. From the results obtained, LN-ODAF demonstrated a potential use of lipid-based nanoparticles as efficient carriers of an active pharmaceutical ingredient (API) involved in the management of retinal diseases.


Assuntos
Córnea/metabolismo , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Lipídeos/química , Nanopartículas/administração & dosagem , Segmento Posterior do Olho/metabolismo , Compostos de Espiro/administração & dosagem , Animais , Córnea/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/química , Segmento Posterior do Olho/efeitos dos fármacos , Coelhos , Compostos de Espiro/química
8.
Int J Mol Sci ; 22(16)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34445639

RESUMO

Nanoparticles bearing specific targeting groups can, in principle, accumulate exclusively at lesion sites bearing target molecules, and release therapeutic agents there. However, practical application of targeted nanoparticles in the living organism presents challenges. In particular, intravasally applied nanoparticles encounter physical and physiological barriers located in blood vessel walls, blocking passage from the blood into tissue compartments. Whereas small molecules can pass out of the blood, nanoparticles are too large and need to utilize physiological carriers enabling passage across endothelial walls. The issues associated with crossing blood-tissue barriers have limited the usefulness of nanoparticles in clinical applications. However, nanoparticles do not encounter blood-tissue barriers if their targets are directly accessible from the blood. This review focuses on osteoporosis, a disabling and common disease for which therapeutic strategies are limited. The target sites for therapeutic agents in osteoporosis are located in bone resorption pits, and these are in immediate contact with the blood. There are specific targetable biomarkers within bone resorption pits. These present nanomedicine with the opportunity to treat a major disease by use of simple nanoparticles loaded with any of several available effective therapeutics that, at present, cannot be used due to their associated side effects.


Assuntos
Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Nanomedicina , Nanopartículas/administração & dosagem , Osteoporose/tratamento farmacológico , Idoso , Humanos , Nanopartículas/química
9.
Molecules ; 26(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34361740

RESUMO

There is a challenging need for the development of new alternative nanostructures that can allow the coupling and/or encapsulation of therapeutic/diagnostic molecules while reducing their toxicity and improving their circulation and in-vivo targeting. Among the new materials using natural building blocks, peptides have attracted significant interest because of their simple structure, relative chemical and physical stability, diversity of sequences and forms, their easy functionalization with (bio)molecules and the possibility of synthesizing them in large quantities. A number of them have the ability to self-assemble into nanotubes, -spheres, -vesicles or -rods under mild conditions, which opens up new applications in biology and nanomedicine due to their intrinsic biocompatibility and biodegradability as well as their surface chemical reactivity via amino- and carboxyl groups. In order to obtain nanostructures suitable for biomedical applications, the structure, size, shape and surface chemistry of these nanoplatforms must be optimized. These properties depend directly on the nature and sequence of the amino acids that constitute them. It is therefore essential to control the order in which the amino acids are introduced during the synthesis of short peptide chains and to evaluate their in-vitro and in-vivo physico-chemical properties before testing them for biomedical applications. This review therefore focuses on the synthesis, functionalization and characterization of peptide sequences that can self-assemble to form nanostructures. The synthesis in batch or with new continuous flow and microflow techniques will be described and compared in terms of amino acids sequence, purification processes, functionalization or encapsulation of targeting ligands, imaging probes as well as therapeutic molecules. Their chemical and biological characterization will be presented to evaluate their purity, toxicity, biocompatibility and biodistribution, and some therapeutic properties in vitro and in vivo. Finally, their main applications in the biomedical field will be presented so as to highlight their importance and advantages over classical nanostructures.


Assuntos
Materiais Biocompatíveis/síntese química , Portadores de Fármacos/síntese química , Nanoestruturas/química , Peptídeos/síntese química , Técnicas de Síntese em Fase Sólida/métodos , Sequência de Aminoácidos , Animais , Materiais Biocompatíveis/farmacocinética , Portadores de Fármacos/farmacocinética , Composição de Medicamentos/métodos , Humanos , Nanoestruturas/administração & dosagem , Nanoestruturas/ultraestrutura , Tamanho da Partícula , Peptídeos/farmacocinética , Distribuição Tecidual
10.
J Agric Food Chem ; 69(34): 9764-9777, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34404210

RESUMO

The marine natural product fucoxanthin has been reported previously to produce anti-Alzheimer's disease (AD) neuroprotective effects in vitro and in vivo. Fucoxanthin was also demonstrated to be safe in preclinical and small population clinical studies, but the low bioavailability of fucoxanthin in the central nervous system (CNS) has limited its clinical applications. To overcome this, poly lactic-co-glycolic acid-block-polyethylene glycol loaded fucoxanthin (PLGA-PEG-Fuc) nanoparticles with diameter at around 200 nm and negative charge were synthesized and suggested to penetrate into the CNS. Loaded fucoxanthin could be liberated from PLGA-PEG nanoparticles by sustained released in the physiological environment. PLGA-PEG-Fuc nanoparticles were shown to significantly inhibit the formation of Aß fibrils and oligomers. Moreover, these nanoparticles were taken up by both neurons and microglia, leading to the reduction of Aß oligomers-induced neurotoxicity in vitro. Most importantly, intravenous injection of PLGA-PEG-Fuc nanoparticles prevented cognitive impairments in Aß oligomers-induced AD mice with greater efficacy than free fucoxanthin, possibly via acting on Nrf2 and NF-κB signaling pathways. These results altogether suggest that PLGA-PEG nanoparticles can enhance the bioavailability of fucoxanthin and potentiate its efficacy for the treatment of AD, thus potentially enabling its future use for AD therapy.


Assuntos
Nanopartículas , Feófitas , Peptídeos beta-Amiloides , Animais , Carotenoides , Portadores de Fármacos , Camundongos , Polietilenoglicóis , Xantofilas
11.
Nat Commun ; 12(1): 4858, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381048

RESUMO

Complement is an enzymatic humoral pattern-recognition defence system of the body. Non-specific deposition of blood biomolecules on nanomedicines triggers complement activation through the alternative pathway, but complement-triggering mechanisms of nanomaterials with dimensions comparable to or smaller than many globular blood proteins are unknown. Here we study this using a library of <6 nm poly(amido amine) dendrimers bearing different end-terminal functional groups. Dendrimers are not sensed by C1q and mannan-binding lectin, and hence do not trigger complement activation through these pattern-recognition molecules. While, pyrrolidone- and carboxylic acid-terminated dendrimers fully evade complement response, and independent of factor H modulation, binding of amine-terminated dendrimers to a subset of natural IgM glycoforms triggers complement activation through lectin pathway-IgM axis. These findings contribute to mechanistic understanding of complement surveillance of dendrimeric materials, and provide opportunities for dendrimer-driven engineering of complement-safe nanomedicines and medical devices.


Assuntos
Ativação do Complemento , Proteínas do Sistema Complemento/metabolismo , Dendrímeros/metabolismo , Imunoglobulina M/metabolismo , Ativação do Complemento/efeitos dos fármacos , Complemento C1q/metabolismo , Dendrímeros/química , Dendrímeros/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Portadores de Fármacos/farmacologia , Humanos , Lectina de Ligação a Manose/metabolismo , Serina Proteases Associadas a Proteína de Ligação a Manose , Poliaminas/química , Poliaminas/metabolismo , Poliaminas/farmacologia
12.
J Biomed Nanotechnol ; 17(7): 1320-1329, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34446135

RESUMO

Nanoparticles (NPs) are a promising strategy for delivering drugs to specific sites because of their tunable size and surface chemistry variety. Among the availablematerials, NPs prepared with biopolymers are of particular interest because of their biocompatibility and controlled release of encapsulated drugs. Poly lactic-co-glycolic acid (PLGA) is one of the most widely used biopolymers in biomedical applications. In addition to material choice modulation of the interaction between NPs and biological systems is essential for the safety and effective use of NPs. Therefore, this work focused on evaluating different surface functionalization strategies to promote cancer cell uptake and intracellular targeting of PLGA NPs. Herein, cell-penetrating peptides (CPPs) were shown to successfully drive PLGA NPs to the mitochondria and nuclei. Furthermore, the functionalization of PLGA NPs with peptide AC-1001 H3 (GQYGNLWFAY) was proven to be useful for targeting actin filaments. The PLGA NPs cell internalization mechanism by B16F10-Nex2 cells was identified as caveolae-mediated endocytosis, which could be inhibited by the presence of methyl-ß-cyclodextrin. Notably, when peptide C (CVNHPAFAC) was used to functionalize PLGA NPs, none of the tested inhibitors could avoid cell internalization of PLGA NPs. Therefore, we suggest this peptide as a promising surface modification agent for enhancing drug delivery to cancer cells. Finally, PLGA NPs showed slow release kinetics and low cytotoxic profile, which, combined with the surface functionalization strategies addressed in this study, highlight the potential of PLGA NPs as a drug delivery platform for improving cancer therapy.


Assuntos
Peptídeos Penetradores de Células , Nanopartículas , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Glicolatos , Glicóis , Ácido Láctico , Ácido Poliglicólico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
13.
Biomater Sci ; 9(17): 5977-5987, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34338256

RESUMO

Nanodrug delivery systems have been used extensively to improve the tumor-targeting ability and reduce the side effects of anticancer drugs. In this study, nanomicelles responsive to dual stimuli were designed and developed as drug carriers for delivering doxorubicin (DOX). The hydrophobic group of the nanomicelles was composed of the photosensitizer protoporphyrin IX (PpIX) and the disulfide bond-containing alpha-lipoic acid (LA); the hydrophilic group was made up of the nuclear localization signal (NLS, CGGGPKKKRKVGG) peptide with a lysine linker. Furthermore, anionic cyclo-γ-polyglutamic acid (cyclo-γ-PGA) was coated on the surface of the cationic micelles to construct a multifunctional drug delivery system (NLS-LA-PpIX-DOX@cyclo-γ-PGA). Cyclo-γ-PGA, as a biological coating material, notably improved the stability of the cationic micelles by reducing nonspecific reactions with anionic groups. Additionally, the cyclo-γ-PGA coating mediated active tumor targeting and enhanced the cellular uptake of micelles via the γ-glutamyl transpeptidase (GGT) pathway. The integrated micelles not only achieved photochemical internalization (PCI) and photodynamic therapy (PDT) via light-activated reactive oxygen species (ROS) but also realized controlled intracellular drug release via the glutathione (GSH)-responsive disulfide-bond cleavage. As a result, NLS-LA-PpIX-DOX@cyclo-γ-PGA exhibited excellent synergistic chemo-photodynamic antitumor activity and fewer side effects than other therapies both in vitro and in vivo. In conclusion, this new dual-responsive drug delivery system (NLS-LA-PpIX-DOX@cyclo-γ-PGA) with improved stability and enhanced tumor-targeting ability may facilitate the development of high-efficiency and low-toxicity nanotherapeutic approaches.


Assuntos
Fotoquimioterapia , Ácido Poliglutâmico , Doxorrubicina/farmacologia , Portadores de Fármacos , Liberação Controlada de Fármacos , Micelas , Ácido Poliglutâmico/análogos & derivados
14.
Front Immunol ; 12: 716407, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394121

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new strain of coronavirus and the causative agent of the current global pandemic of coronavirus disease 2019 (COVID-19). There are currently no FDA-approved antiviral drugs for COVID-19 and there is an urgent need to develop treatment strategies that can effectively suppress SARS-CoV-2 infection. Numerous approaches have been researched so far, with one of them being the emerging exosome-based therapies. Exosomes are nano-sized, lipid bilayer-enclosed structures, share structural similarities with viruses secreted from all types of cells, including those lining the respiratory tract. Importantly, the interplay between exosomes and viruses could be potentially exploited for antiviral drug and vaccine development. Exosomes are produced by virus-infected cells and play crucial roles in mediating communication between infected and uninfected cells. SARS-CoV-2 modulates the production and composition of exosomes, and can exploit exosome formation, secretion, and release pathways to promote infection, transmission, and intercellular spread. Exosomes have been exploited for therapeutic benefits in patients afflicted with various diseases including COVID-19. Furthermore, the administration of exosomes loaded with immunomodulatory cargo in combination with antiviral drugs represents a novel intervention for the treatment of diseases such as COVID-19. In particular, exosomes derived from mesenchymal stem cells (MSCs) are used as cell-free therapeutic agents. Mesenchymal stem cell derived exosomes reduces the cytokine storm and reverse the inhibition of host anti-viral defenses associated with COVID-19 and also enhances mitochondrial function repair lung injuries. We discuss the role of exosomes in relation to transmission, infection, diagnosis, treatment, therapeutics, drug delivery, and vaccines, and present some future perspectives regarding their use for combating COVID-19.


Assuntos
Antivirais/administração & dosagem , Antivirais/uso terapêutico , COVID-19/terapia , Portadores de Fármacos/uso terapêutico , Exossomos/metabolismo , Imunomodulação/imunologia , Biomarcadores/metabolismo , COVID-19/patologia , COVID-19/transmissão , Síndrome da Liberação de Citocina/terapia , Humanos , Células-Tronco Mesenquimais/imunologia , SARS-CoV-2/imunologia
15.
Nat Commun ; 12(1): 4755, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362890

RESUMO

Some specific chemotherapeutic drugs are able to enhance tumor immunogenicity and facilitate antitumor immunity by inducing immunogenic cell death (ICD). However, tumor immunosuppression induced by the adenosine pathway hampers this effect. In this study, E-selectin-modified thermal-sensitive micelles are designed to co-deliver a chemotherapeutic drug (doxorubicin, DOX) and an A2A adenosine receptor antagonist (SCH 58261), which simultaneously exhibit chemo-immunotherapeutic effects when applied with microwave irradiation. After intravenous injection, the fabricated micelles effectively adhere to the surface of leukocytes in peripheral blood mediated by E-selectin, and thereby hitchhiking with leukocytes to achieve a higher accumulation at the tumor site. Further, local microwave irradiation is applied to induce hyperthermia and accelerates the release rate of drugs from micelles. Rapidly released DOX induces tumor ICD and elicits tumor-specific immunity, while SCH 58261 alleviates immunosuppression caused by the adenosine pathway, further enhancing DOX-induced antitumor immunity. In conclusion, this study presents a strategy to increase the tumor accumulation of drugs by hitchhiking with leukocytes, and the synergistic strategy of chemo-immunotherapy not only effectively arrested primary tumor growth, but also exhibited superior effects in terms of antimetastasis, antirecurrence and antirechallenge.


Assuntos
Tratamento Farmacológico , Imunoterapia , Leucócitos/efeitos dos fármacos , Micelas , Neoplasias/terapia , Animais , Doxorrubicina/farmacologia , Portadores de Fármacos/administração & dosagem , Liberação Controlada de Fármacos , Feminino , Hipertermia/terapia , Imunidade , Camundongos , Camundongos Endogâmicos BALB C , Micro-Ondas/uso terapêutico , Fototerapia
16.
Drug Des Devel Ther ; 15: 3313-3330, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34366663

RESUMO

The acute respiratory syndrome coronavirus (SARS-CoV-2) has spread across the world, resulting in a pandemic COVID-19 which is a human zoonotic disease that is caused by a novel coronavirus (CoV) strain thought to have originated in wild or captive bats in the initial COVID outbreak region. The global COVID-19 outbreak started in Guangdong Province, China's southernmost province. The global response to the COVID-19 pandemic has been hampered by the sheer number of infected people, many of whom need intensive care before succumbing to the disease. The epidemic is being handled by a combination of disease control by public health interventions and compassionate treatment for those who have been impacted. There is no clear anti-COVID-19 medication available at this time. However, the need to find medications that can turn the tide has led to the development of a number of investigational drugs as potential candidates for improving outcomes, especially in the severely and critically ill. Although many of these adjunctive medications are still being studied in clinical trials, professional organizations have attempted to define the circumstances in which their use is deemed off-label or compassionate. It is important to remind readers that new information about COVID-19's clinical features, treatment options, and outcomes is released on a regular basis. The mainstay of treatment remains optimized supportive care, and the therapeutic effectiveness of the subsequent agents is still being studied.


Assuntos
Antivirais/administração & dosagem , Vacinas contra COVID-19/administração & dosagem , COVID-19/tratamento farmacológico , Portadores de Fármacos , Reposicionamento de Medicamentos , Modelos Moleculares , Animais , Antivirais/química , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/virologia , Vacinas contra COVID-19/química , Composição de Medicamentos , Interações Hospedeiro-Patógeno , Humanos , Nanopartículas , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/patogenicidade , Vacinação
17.
Food Res Int ; 147: 110564, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34399540

RESUMO

Nanogel carriers are rapidly emerged as a major delivery strategy in the fields of food, biology and medicine for small particle size, excellent solubility, high loading, and controlled release. Natural polysaccharides and proteins are selected for the preparation of biocompatible, biodegradable, low toxic, and less immunogenic nanogels. Different polysaccharides and proteins form complex nanogels through different interaction forces (e.g., electrostatic interaction and hydrophobic interaction). The present review pursues three aims: 1) to introduce several well-known dietary polysaccharides (chitosan, dextran and alginate) and proteins (whey protein and lysozyme); 2) to discuss the types, preparation methods, chemical interactions and properties of various biocompatible complex carriers; 3) to present the application and prospect of polysaccharide-protein complex in bioactive ingredient delivery, nutrient encapsulation and flavor protection. We expect that the integration with nano-intelligent technology will improve the functional ingredient loading, recognition specificity and controlled release capabilities of polysaccharide-protein nanocomposites to generate new intelligent nanogels in the field of food industry in the future.


Assuntos
Portadores de Fármacos , Polietilenoimina , Nanogéis , Polietilenoglicóis , Polissacarídeos
18.
Molecules ; 26(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34443323

RESUMO

Polysaccharides are a versatile class of macromolecules that are involved in many biological interactions critical to life. They can be further modified for added functionality. Once derivatized, these polymers can exhibit new chemical properties that can be further optimized for applications in drug delivery, wound healing, sensor development and others. Chitosan, derived from the N-deacetylation of chitin, is one example of a polysaccharide that has been functionalized and used as a major component of polysaccharide biomaterials. In this brief review, we focus on one aspect of chitosan's utility, namely we discuss recent advances in dual-responsive chitosan hydrogel nanomaterials.


Assuntos
Quitosana/química , Portadores de Fármacos/química , Hidrogéis/química , Nanocompostos/química , Animais , Humanos
19.
Molecules ; 26(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34443336

RESUMO

We develop a suitable delivery system for niaouli essential oil (NEO) using a nanoemulsification method for acne vulgaris. Prepared nanoemulsions (NEs) were characterized for droplet dimension, rheology, surface charge, and stability. The ability of NEO formulations against Propionibacterium acnes and Staphylococcus epidermidis was investigated and all formulations showed antiacne potential in vitro. Ex vivo permeation studies indicated significant improvement in drug permeations and steady state flux of all NEO-NEs compared to the neat NEO (p < 0.05). On the basis of the studied pharmaceutical parameters, enhanced ex vivo skin permeation, and marked effect on acne pathogens, formulation NEO-NE4 was found to be the best (oil (NEO; 10% v/v); Kolliphor EL (9.25% v/v), Carbitol (27.75% v/v), and water (53% v/v)). Concisely, the in vitro and ex vivo results revealed that nanoemulsification improved the delivery as well as bioactivities of NEO significantly.


Assuntos
Portadores de Fármacos/química , Melaleuca/química , Nanoestruturas/química , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Emulsões , Óleos Voláteis/metabolismo , Permeabilidade , Pele/metabolismo , Staphylococcus epidermidis/efeitos dos fármacos
20.
Molecules ; 26(16)2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34443357

RESUMO

In this work, we propose the utilization of scCO2 to impregnate ibuprofen into the mcl-PHA matrix produced by Pseudomonas chlororaphis subs. aurantiaca (DSM 19603). The biopolymer has adhesive properties, is biocompatible and has a melting temperature of 45 °C. Several conditions, namely, pressure (15 and 20 MPa) and impregnation time (30 min, 1 h and 3 h) were tested. The highest ibuprofen content (90.8 ± 6.5 mg of ibuprofen/gPHA) was obtained at 20 MPa and 40 °C, for 1 h, with an impregnation rate of 89 mg/(g·h). The processed mcl-PHA samples suffered a plasticization, as shown by the decrease of 6.5 °C in the Tg, at 20 MPa. The polymer's crystallinity was also affected concomitantly with the matrices' ibuprofen content. For all the impregnation conditions tested the release of ibuprofen from the biopolymer followed a type II release profile. This study has demonstrated that the mcl-PHA produced by P. chlororaphis has a great potential for the development of novel topical drug delivery systems.


Assuntos
Dióxido de Carbono/química , Portadores de Fármacos/química , Ibuprofeno/química , Poli-Hidroxialcanoatos/química , Adesividade , Liberação Controlada de Fármacos , Temperatura
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