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1.
J Colloid Interface Sci ; 606(Pt 2): 1737-1744, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34507167

RESUMO

A protein corona forms around nanoparticles when they are intravenously injected into the bloodstream. The composition of the protein corona dictates the interactions between nanoparticles and the biological systems thus their immune evasion, blood circulation, and biodistribution. Here, we report for the first time the impact of nanoparticle stiffness on protein corona formation using a unique emulsion core silica shell nanocapsules library with a wide range of mechanical properties over four magnitudes (700 kPa to 10 GPa). The nanocapsules with different stiffness showed distinct proteomic fingerprints. The protein corona of the stiffest nanocapsules contained the highest amount of complement protein (Complement C3) and immunoglobulin proteins, which contributed to their high macrophage uptake, confirming the important role of nanocapsules stiffness in controlling the protein corona formation thus their in vitro and in vivo behaviors.


Assuntos
Nanopartículas , Coroa de Proteína , Adsorção , Proteômica , Distribuição Tecidual
2.
Acta Biomater ; 130: 98-114, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34126265

RESUMO

Liver diseases have become an increasing health burden and account for over 2 million deaths every year globally. Standard therapies including liver transplant and cell therapy offer a promising treatment for liver diseases, but they also suffer limitations such as adverse immune reactions and lack of long-term efficacy. Artificial cells that mimic certain functions of a living cell have emerged as a new strategy to overcome some of the challenges that liver cell therapy faces at present. Artificial cells have demonstrated advantages in long-term storage, targeting capability, and tuneable features. This article provides an overview of the recent progress in developing artificial cells and their potential applications in liver disease treatment. First, the design of artificial cells and their biomimicking functions are summarized. Then, systems that mimic cell surface properties are introduced with two concepts highlighted: cell membrane-coated artificial cells and synthetic lipid-based artificial cells. Next, cell microencapsulation strategy is summarized and discussed. Finally, challenges and future perspectives of artificial cells are outlined. STATEMENT OF SIGNIFICANCE: Liver diseases have become an increasing health burden. Standard therapies including liver transplant and cell therapy offer a promising treatment for liver diseases, but they have limitations such as adverse immune reactions and lack of long-term efficacy. Artificial cells that mimic certain functions of a living cell have emerged as a new strategy to overcome some of the challenges that liver cell therapy faces at present. This article provides an overview of the recent progress in developing artificial cells and their potential applications in liver disease treatment, including the design of artificial cells and their biomimicking functions, two systems that mimic cell surface properties (cell membrane-coated artificial cells and synthetic lipid-based artificial cells), and cell microencapsulation strategy. We also outline the challenges and future perspectives of artificial cells.


Assuntos
Células Artificiais , Hepatopatias , Membrana Celular , Hepatócitos , Humanos , Hepatopatias/terapia
3.
Colloids Surf B Biointerfaces ; 206: 111923, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34146992

RESUMO

Labeling nanoparticles with fluorescent dyes is a common approach to investigate their cell uptake and biodistribution, providing valuable information for the preclinical assessment of nanoparticles for drug delivery. However, the underlying assumption that the fluorescence intensity of dye-labeled nanoparticles correlates positively with the amount of nanoparticles taken up by cells might not be valid under some conditions, as it can be affected by many factors including dye dispersion, dye quenching, and material shading. Here we demonstrated that both nanoparticles with hydrophobic dyes encapsulated inside and nanoparticles with hydrophilic dyes conjugated on the particle surface suffer from different degrees of dye quenching, making it challenging for quantitative comparison of cell uptake of different nanoparticles. To address this challenge, we proposed a possible solution for direct comparative studies of dye-labeled nanoparticles. This work provides valuable information for designing and evaluating different nanoparticles for drug delivery applications.


Assuntos
Corantes Fluorescentes , Nanopartículas , Interações Hidrofóbicas e Hidrofílicas , Distribuição Tecidual
4.
J Colloid Interface Sci ; 601: 78-84, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34058554

RESUMO

Iron oxide nanoparticles have been extensively studied for a wide variety of applications. However, there remains a challenge in developing hierarchical magnetic iron oxide nanoparticles as existing synthetic techniques require harsh, toxic chemical conditions and high temperatures or give poorly defined product with weak magnetic properties. In addition, drug loading is limited to post-loading methods such as chemical conjugation or surface adsorption that have poor loading efficiency and are prone to premature drug release. We report a facile biomimetic method for making iron oxide nanoparticle-loaded silica nanocapsules based on a bimodal catalytic peptide surfactant stabilized nanoemulsion template. Iron oxide nanoparticles can be preloaded into the oil phase of the nanoemulsion at tunable concentrations, and the excellent surface activity of the designed bimodal peptide in combination with sufficient electrostatic repulsion promotes the stability of the nanoemulsions. Biosilicification induced by the catalytic peptide module leads to the formation of silica shell nanocapsules containing a magnetic oil core. The bioinspired silica nanocapsules encapsulating iron oxide nanoparticles demonstrate the next-generation of magnetic nanostructures for drug delivery applications.


Assuntos
Nanocápsulas , Sistemas de Liberação de Medicamentos , Compostos Férricos , Dióxido de Silício
5.
Pharmacol Res ; 169: 105608, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33852961

RESUMO

The past decade has seen many advancements in the development of three-dimensional (3D) in vitro models in pharmaceutical sciences and industry. Specifically, organoids present a self-organising, self-renewing and more physiologically relevant model than conventional two-dimensional (2D) cell cultures. Liver organoids have been developed from a variety of cell sources, including stem cells, cell lines and primary cells. They have potential for modelling patient-specific disease and establishing personalised therapeutic approaches. Additionally, liver organoids have been used to test drug efficacy and toxicity. Herein we summarise cell sources for generating liver organoids, the advantages and limitations of each cell type, as well as the application of the organoids in modelling liver diseases. We focus on the use of liver organoids as tools for drug validation and toxicity assessment.

6.
J Colloid Interface Sci ; 594: 474-484, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33774403

RESUMO

Polymer nanoparticles (NPs) have attracted significant interest in the past years for drug delivery and triggered release. However, it remains a significant challenge to produce polymer NPs with controlled properties and tunable drug loading. Traditional nanoprecipitation often leads to low drug loading. This study reports the development of a new microfluidic nanoprecipitation approach for making polymer NPs with tunable drug loading up to 50%. The synthesized curcumin-loaded shellac NPs remain very stable for the period of our experiments (10 days) under acidic conditions (pH 4.5), but release the payload at neutral pH in a sustained manner. This work provides a new strategy for making drug-loaded polymer NPs with tunable drug loading and triggered release.


Assuntos
Curcumina , Nanopartículas , Preparações Farmacêuticas , Portadores de Fármacos , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Microfluídica , Tamanho da Partícula , Polímeros
7.
Angew Chem Int Ed Engl ; 60(17): 9284-9289, 2021 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-33586298

RESUMO

Most tumors have more severe hypoxia levels than normal tissue; tumor hypoxia is thus a useful target for cancer treatment. Here, we develop an effective oxygen delivery vehicle of polydopamine-nanoparticle-stabilized oxygen microcapsules by interfacial polymerization. The oxygen microcapsules have excellent biocompatibility. Oxygen could easily diffuse out from the microcapsules, thus increasing and maintaining the microenvironment at an oxygen-rich state. In vitro cell cultures confirm that oxygen microcapsules could effectively improve the hypoxia microenvironment, showing the lowest fluorescent intensity of hypoxia-green-labeled cells. When injected subcutaneously in vivo, oxygen microcapsules could also improve the tumor's hypoxia microenvironment, thus suppressing the growth of tumor. Synergetic therapy using oxygen microcapsules and gemcitabine drugs is an effective way for tumor treatment, showing the best performance in suppressing the tumor's growth.


Assuntos
Materiais Biocompatíveis/química , Sistemas de Liberação de Medicamentos , Indóis/química , Nanopartículas/química , Oxigênio/química , Polímeros/química , Cápsulas , Indóis/síntese química , Estrutura Molecular , Tamanho da Partícula , Polimerização , Polímeros/síntese química
8.
J Colloid Interface Sci ; 584: 528-538, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33129162

RESUMO

Many uses of emulsion droplets require precise control over droplet size and shape. Here we report a 'shape-memorable' micro-droplet formulation stabilized by a polyethylene glycol (PEG)-modified protein -surfactant, the droplets are stable against coalescence for months and can maintain non-spherical shapes for hours, depending on the surface coverage of PEGylated protein. Monodisperse droplets with aspect ratios ranging from 1.0 to 3.4 were controllably synthesized with a flow-focusing microfluidic device. Mechanical properties of the interfacial protein network were explored to elucidate the mechanism behind the droplet shape conservation phenomenon. Characterization of the protein film revealed that the presence of a PEG layer at interfaces alters the mechanical responses of the protein film, resulting in interfacial networks with improved strength. Taking advantage of the prolonged stabilization of non-spherical droplets, we demonstrate functionalization of the droplet interface with accessible biotins. The stabilization of micro-droplet shape with surface-active proteins that also serve as an anchor for integrating functional moieties, provides a tailorable interface for diverse biomimetic applications.


Assuntos
Microfluídica , Tensoativos , Emulsões , Polietilenoglicóis
9.
Chempluschem ; 86(1): 49-58, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32894011

RESUMO

Nanoparticles with diverse structures and unique properties have attracted increasing attention for their widespread applications. Co-precipitation under rapid mixing is an effective method to obtained biocompatible nanoparticles and diverse particle carriers are achieved by controlled phase separation via interfacial tensions. In this Minireview, we summarize the underlying mechanism of co-precipitation and show that rapid mixing is important to ensure co-precipitation. In the binary polymer system, the particles can form four different morphologies, including occluded particle, core-shell capsule, dimer particle, and heteroaggregate, and we demonstrate that the final morphology could be controlled by surface tensions through surfactant, polymer composition, molecular weight, and temperature. The applications of occluded particles, core-shell capsules and dimer particles prepared by co-precipitation or microfluidics upon the regulation of interfacial tensions are discussed in detail, and show great potential in the areas of functional materials, colloidal surfactants, drug delivery, nanomedicine, bio-imaging, displays, and cargo encapsulation.

10.
Biomacromolecules ; 22(2): 330-339, 2021 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-33305948

RESUMO

Antifouling surfaces are important in a broad range of applications. An effective approach to antifouling surfaces is to covalently attach antifouling polymer brushes. This work reports the synthesis of a new class of antifouling polymer brushes based on highly hydrophilic sulfoxide polymers by surface-initiated photoinduced electron/energy transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization. The sulfoxide polymer brushes are able to effectively reduce nonspecific adsorption of proteins and cells, demonstrating remarkable antifouling properties. Given the outstanding antifouling behavior of the sulfoxide polymers and versatility of surface-initiated PET-RAFT technology, this work presents a useful and general approach to engineering various material surfaces with antifouling properties, for potential biomedical applications in areas such as tissue engineering, medical implants, and regenerative medicine.


Assuntos
Incrustação Biológica , Polímeros , Incrustação Biológica/prevenção & controle , Interações Hidrofóbicas e Hidrofílicas , Polimerização , Sulfóxidos , Propriedades de Superfície
11.
J Colloid Interface Sci ; 581(Pt A): 185-194, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32771730

RESUMO

Biomimetic nanomaterials have attracted tremendous research interest in the past decade. We recently developed biomimetic core-shell nanoparticles - silica nanocapsules, using a designer dual-functional peptide SurSi under room temperature, neutral pH and without use of any toxic reagents or chemicals. The SurSi peptide is designed capable of not only stabilizing nanoemulsions because of its excellent surface activity, but also inducing the formation of silica through biosilicification at an oil-water interface. However, it remains challenging to precisely control the peptide-induced nucleation and biosilicification specifically at the oil-water interface, thus forming oil-core silica-shell nanocapsules with uniform size and monodispersity. In this study, the fundamental mechanism of silica formation through a peptide catalyzed biosilicification was systematically investigated, so that the formation of oil-core silica-shell nanocapsules can be precisely controlled. The SurSi peptide induced hydrolysis and nucleation of biomineralized silica particles were monitored to study the biosilicification kinetics. Effects of pH, SurSi peptide concentration and pre-hydrolysis of silica precursors were also studied to optimize the formation of biomimetic silica nanocapsules. The fundamental understanding achieved through these systematic studies provides valuable insights for making core-shell nanoparticles via controlling nucleation and reaction at interfaces.


Assuntos
Nanocápsulas , Nanopartículas , Biomimética , Peptídeos , Dióxido de Silício
12.
J Adolesc Health ; 67(5S): S48-S54, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33246533

RESUMO

PURPOSE: Children who are left behind when their parents migrate for work have a high prevalence of emotional and behavioral problems, which affect social function and increase family burden. To date, no national survey has been conducted on the emotional and behavioral problems of left-behind children (LBC) in China. This study aimed to investigate the emotional and behavioral outcomes of primary school LBC in the fourth grade in impoverished rural China and the possible influences of family environment and parenting practices. METHODS: A cross-sectional study was carried out in 27 rural counties in the central and western parts of China from November 2016 to January 2017. The method of quota sampling was adopted to achieve a representative sample using postweighting adjustment. The survey sample was distributed proportionately across each county. LBC were defined as children aged <16 years who had two parents leave home to work or one parent leave home while the other lost the capacity to rear their children. The term "non-left-behind children" (NLBC) refers to children who have at least one parent who has not migrated for work. The Strengths and Difficulty Questionnaire (SDQ) was applied to measure children's emotional and behavioral problems. RESULTS: After the weighted calculations were performed, there were 1,147 LBC and 3,953 NLBC. The proportion of abnormal SDQ total scores (>17) was significantly higher in the LBC group than in the NLBC group (15.6% vs. 11.6%; p < .01). Binary regression analysis showed that high levels of insomnia (odds ratio [OR] 1.54, 95% confidence interval [CI] 1.04-2.27), loneliness (OR 1.65, 95% CI 1.13-2.43), and self-harm (OR 1.92, 95% CI 1.17-3.16) may increase the risk of abnormal SDQ total scores in LBC. CONCLUSIONS: LBC showed a higher prevalence of abnormal SDQ total scores than NLBC. Insomnia, loneliness, and self-harm behavior were associated with abnormal SDQ total scores in LBC.


Assuntos
Sintomas Afetivos , Ansiedade de Separação , Comportamento Infantil/psicologia , Separação da Família , Comportamento Problema/psicologia , População Rural/estatística & dados numéricos , Adolescente , Criança , China/epidemiologia , Estudos Transversais , Humanos , Pais , Inquéritos e Questionários
13.
Channels (Austin) ; 14(1): 326-335, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32988261

RESUMO

Ca2+-induced Ca2+ release (CICR) from sarcoplasmic reticulum is a finely tuned process responsible for cardiac excitation and contraction. The ubiquitin-proteasome system (UPS) as a major degradative system plays a crucial role in the maintenance of Ca2+ homeostasis. The E3 component N-recognin (UBR) subfamily is a part of the UPS; however, the role of UBR in regulating cardiac CICR is unknown. In the present study, we found that among the UBR family, single knockdown of UBR3 or UBR6 significantly elevated the amplitude of sarcoplasmic reticulum Ca2+ release without affecting Ca2+ transient decay time in neonatal rat ventricular myocytes. The protein expression of alpha 1 C subunit of L-type voltage-dependent Ca2+ channel (Cav1.2) was increased after UBR3/6 knockdown, whereas the protein levels of RyR2, SERCA2a, and PLB remained unchanged. In line with the increase in Cav1.2 proteins, the UBR3/6 knockdown enhanced the current of Cav1.2 channels. Furthermore, the increase in Cav1.2 proteins caused by UBR3/6 reduction was not counteracted by a protein biosynthesis inhibitor, cycloheximide, suggesting a degradative regulation of UBR3/6 on Cav1.2 channels. Our results indicate that UBR3/6 modulates cardiac CICR via targeting Cav1.2 protein degradation.


Assuntos
Cálcio/metabolismo , Miócitos Cardíacos/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Canais de Cálcio Tipo L/metabolismo , Técnicas de Silenciamento de Genes , Ventrículos do Coração/citologia , Proteólise , Ratos , Ratos Sprague-Dawley , Ubiquitina-Proteína Ligases/deficiência , Ubiquitina-Proteína Ligases/genética
14.
Chempluschem ; 85(9): 2143-2157, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32864902

RESUMO

Formulating drugs into nanoparticles offers many attractive advantages over free drugs including improved bioavailability, minimized toxic side effects, enhanced drug delivery, feasibility of incorporating other functions such as controlled release, imaging agents for imaging, targeting delivery, and loading more than one drug for combination therapies. One of the key parameters is drug loading, which is defined as the mass ratio of drug to drug-loaded nanoparticles. Currently, most nanoparticle systems have relatively low drug loading (<10 wt%), and developing methods to increase drug loading remains a challenge. This Minireview presents an overview of recent research on developing nanoparticles with high drug loading (>10 wt%) from the perspective of synthesis strategies, including post-loading, co-loading, and pre-loading. Based on these three different strategies, various nanoparticle systems with different materials and drugs are summarized and discussed in terms of their synthesis methods, drug loadings, encapsulation efficiencies, release profiles, stabilities, and their applications in drug delivery. The advantages and disadvantages of these strategies are presented with an objective of providing useful design rules for future development of high-drug-loading nanoparticles.


Assuntos
Portadores de Fármacos , Nanopartículas/química , Composição de Medicamentos
15.
Angew Chem Int Ed Engl ; 59(45): 20065-20074, 2020 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-32743867

RESUMO

Understanding drug-release kinetics is critical for the development of drug-loaded nanoparticles. We developed a J-aggregate-based Förster-resonance energy-transfer (FRET) method to investigate the release of novel high-drug-loading (50 wt %) nanoparticles in comparison with low-drug-loading (0.5 wt %) nanoparticles. Single-dye-loaded nanoparticles form J-aggregates because of the high dye-loading (50 wt %), resulting in a large red-shift (≈110 nm) in the fluorescence spectrum. Dual-dye-loaded nanoparticles with high dye-loading using FRET pairs exhibited not only FRET but also a J-aggregate red-shift (116 nm). Using this J-aggregate-based FRET method, dye-core-polymer-shell nanoparticles showed two release processes intracellularly: the dissolution of the dye aggregates into dye molecules and the release of the dye molecules from the polymer shell. Also, the high-dye-loading nanoparticles (50 wt %) exhibited a slow release kinetics in serum and relatively quick release in cells, demonstrating their great potential in drug delivery.


Assuntos
Portadores de Fármacos/química , Transferência Ressonante de Energia de Fluorescência/métodos , Nanopartículas/química , Polímeros/química , Liberação Controlada de Fármacos , Microscopia Eletrônica de Transmissão
16.
Nat Commun ; 11(1): 4192, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32826886

RESUMO

Bioluminescence imaging has been widely used in life sciences and biomedical applications. However, conventional bioluminescence imaging usually operates in the visible region, which hampers the high-performance in vivo optical imaging due to the strong tissue absorption and scattering. To address this challenge, here we present bioluminescence probes (BPs) with emission in the second near infrared (NIR-II) region at 1029 nm by employing bioluminescence resonance energy transfer (BRET) and two-step fluorescence resonance energy transfer (FRET) with a specially designed cyanine dye FD-1029. The biocompatible NIR-II-BPs are successfully applied to vessels and lymphatics imaging in mice, which gives ~5 times higher signal-to-noise ratios and ~1.5 times higher spatial resolution than those obtained by NIR-II fluorescence imaging and conventional bioluminescence imaging. Their capability of multiplexed imaging is also well displayed. Taking advantage of the ATP-responding character, the NIR-II-BPs are able to recognize tumor metastasis with a high tumor-to-normal tissue ratio at 83.4.


Assuntos
Trifosfato de Adenosina/metabolismo , Medições Luminescentes/métodos , Metástase Neoplásica/diagnóstico por imagem , Imagem Óptica/métodos , Animais , Técnicas Biossensoriais , Linhagem Celular Tumoral , Feminino , Transferência Ressonante de Energia de Fluorescência/instrumentação , Transferência Ressonante de Energia de Fluorescência/métodos , Xenoenxertos , Humanos , Medições Luminescentes/instrumentação , Camundongos , Imagem Óptica/instrumentação , Neoplasias Ovarianas/diagnóstico por imagem
17.
Small ; 16(30): e2002716, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32578400

RESUMO

Co-precipitation is generally refers to the co-precipitation of two solids and is widely used to prepare active-loaded nanoparticles. Here, it is demonstrated that liquid and solid can precipitate simultaneously to produce hierarchical core-shell nanocapsules that encapsulate an oil core in a polymer shell. During the co-precipitation process, the polymer preferentially deposits at the oil/water interface, wetting both the oil and water phases; the behavior is determined by the spreading coefficients and driven by the energy minimization. The technique is applicable to directly encapsulate various oil actives and avoid the use of toxic solvent or surfactant during the preparation process. The obtained core-shell nanocapsules harness the advantage of biocompatibility, precise control over the shell thickness, high loading capacity, high encapsulation efficiency, good dispersity in water, and improved stability against oxidation. The applications of the nanocapsules as delivery vehicles are demonstrated by the excellent performances of natural colorant and anti-cancer drug-loaded nanocapsules. The core-shell nanocapsules with a controlled hierarchical structure are, therefore, ideal carriers for practical applications in food, cosmetics, and drug delivery.


Assuntos
Nanocápsulas , Sistemas de Liberação de Medicamentos , Polímeros , Tensoativos , Água
18.
Colloids Surf B Biointerfaces ; 193: 111108, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32408256

RESUMO

Biomineralization of metal organic frameworks (MOFs) using biomolecules has recently attracted significant interest because of the benign process including room temperature, neutral pH and without the requirement of any other chemical reagents. Also, these biomolecule incorporated MOFs (biomolecules@MOFs) have demonstrated their potential in biomolecule encapsulation, protection and controlled release. This work aims to develop a general strategy to make biomolecules@MOFs via a biomimetic mineralization process. A library of biomolecules (peptides and proteins) with different charges were systematically studied to fundamentally understand the role of biomolecules and their proprieties in biomolecule-mediated MOF biomineralization. Biomolecule charge, amino acid sequence and stirring speed have been demonstrated to play important roles in controlling biomineralization reaction rate, particle shape and morphology.


Assuntos
Materiais Biocompatíveis/química , Estruturas Metalorgânicas/química , Peptídeos/química , Proteínas/química , Materiais Biocompatíveis/síntese química , Estruturas Metalorgânicas/síntese química , Tamanho da Partícula , Propriedades de Superfície
19.
Sci Adv ; 6(16): eaaz4316, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32426455

RESUMO

The ability of cells to sense external mechanical cues is essential for their adaptation to the surrounding microenvironment. However, how nanoparticle mechanical properties affect cell-nanoparticle interactions remains largely unknown. Here, we synthesized a library of silica nanocapsules (SNCs) with a wide range of elasticity (Young's modulus ranging from 560 kPa to 1.18 GPa), demonstrating the impact of SNC elasticity on SNC interactions with cells. Transmission electron microscopy revealed that the stiff SNCs remained spherical during cellular uptake. The soft SNCs, however, were deformed by forces originating from the specific ligand-receptor interaction and membrane wrapping, which reduced their cellular binding and endocytosis rate. This work demonstrates the crucial role of the elasticity of nanoparticles in modulating their macrophage uptake and receptor-mediated cancer cell uptake, which may shed light on the design of drug delivery vectors with higher efficiency.

20.
Int J Pharm ; 581: 119291, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32259638

RESUMO

Ketamine in sub-anaesthetic doses is an analgesic adjuvant with a morphine-sparing effect. Co-administration of a strong opioid with an analgesic adjuvant such as ketamine is a potential treatment option, especially for patients with cancer-related pain. A limitation of ketamine is its short in vivo elimination half-life. Hence, our aim was to develop biocompatible and biodegradable ketamine-loaded poly(ethylene glycol) (PEG)-block-poly(lactic-co-glycolic acid) (PLGA) nanoparticles for sustained release. Ketamine-encapsulated single polymer PEG-PLGA nanoparticles and double polymer PEG-PLGA/shellac (SH) nanoparticles with a high drug loading of 41.8% (drug weight/the total weight of drug-loaded nanoparticles) were prepared using a new sequential nanoprecipitation method. These drug-loaded nanoparticles exhibited a sustained-release profile for up to 21 days in vitro and for more than 5 days after intravenous injection in mice. Our study demonstrates that high drug loading and a sustained release profile can be achieved with ketamine-loaded PEG-PLGA nanoparticles prepared using this new nanoprecipitation method.


Assuntos
Precipitação Química , Portadores de Fármacos/síntese química , Ketamina/síntese química , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/síntese química , Analgésicos/administração & dosagem , Analgésicos/química , Analgésicos/metabolismo , Animais , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/metabolismo , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/metabolismo , Ketamina/administração & dosagem , Ketamina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/administração & dosagem , Nanopartículas/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/metabolismo , Distribuição Tecidual/efeitos dos fármacos , Distribuição Tecidual/fisiologia
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