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1.
Drug Deliv Transl Res ; 14(9): 2461-2473, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38296909

RESUMO

Artemisia argyi, commonly known as wormwood, is a traditional Chinese herbal food and medicine celebrated for its notable antibacterial and anti-inflammatory properties. This study explores a novel delivery method for wormwood, aiming for more convenient and versatile applications. Specifically, we present the first investigation into combining wormwood with microstructures to create a microneedle (MN) patch for wound healing. The wormwood microneedle (WMN) patch is formulated with milled wormwood sap, calcium carbonate, and sodium hyaluronate. The addition of 0.3% (w/v) sodium hyaluronate enhances the mechanical strength of the WMN patch. Pectin, derived from wormwood, is combined with calcium carbonate to create a gelatinous and solidified substance. The WMN patch exhibits a well-defined shape and sufficient mechanical strength to penetrate the epidermis, as confirmed by our results. In vitro experiments demonstrate the biocompatibility of the WMN patch with fibroblasts and highlight its antibacterial and anti-inflammatory properties. Furthermore, the patch facilitates collagen deposition at the wound site. In an excisional rat model, the WMN patch significantly accelerates the wound closure rate compared to the control group. Our findings suggest that the WMN patch has the potential to serve as a natural treatment for wound healing. Additionally, this approach can be extended to other biologically active substances with similar physiochemical characteristics in future applications.


Assuntos
Artemisia , Agulhas , Ratos Sprague-Dawley , Cicatrização , Cicatrização/efeitos dos fármacos , Animais , Artemisia/química , Masculino , Antibacterianos/administração & dosagem , Antibacterianos/química , Ácido Hialurônico/química , Ácido Hialurônico/administração & dosagem , Ratos , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Fibroblastos/efeitos dos fármacos , Pectinas/química , Pectinas/administração & dosagem , Camundongos , Humanos
2.
Int J Pharm ; 649: 123669, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38056797

RESUMO

Multidrug resistance (MDR) is a public health issue of particular concern, for which nanotechnology-based multidrug delivery systems are considered among the most effective suppressive strategies for such resistance in tumors. However, for such strategies to be viable, the notable shortcomings of reduced loading efficiency and uncontrollable drug release ratio need to be addressed. To this end, we developed a novel "multidrug/material" co-delivery system, using d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS, P-gp efflux pump inhibitor) and poly(amidoamine) (PAMAM) to fabricate a precursor material with the properties of reversing MDR and having a long-cycle. Further, to facilitate multidrug co-delivery, we loaded doxorubicin(Dox) and curcumin(Cur, cardiotoxicity modifier and P-gp inhibitor) into PAMAM-TPGS nano-micelles respectively, and mixed in appropriate proportions. The multidrug/material co-delivery system thus obtained was characterized by high drug loading and a controllable drug release ratio in the physiological environment. More importantly, in vitro and in vivo pharmacodynamic studies indicated that the multidrug/material co-delivery system facilitated the reversal of MDR. Moreover, the system has increased anti-tumor activity and is biologically safe. We accordingly propose that the "multidrug/material" co-delivery system developed in this study could serve as a potential platform for reversing MDR and achieving safe and effective clinical treatment.


Assuntos
Antineoplásicos , Resistencia a Medicamentos Antineoplásicos , Humanos , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Resistência a Múltiplos Medicamentos , Micelas , Vitamina E/farmacologia , Polietilenoglicóis/farmacologia , Antineoplásicos/farmacologia , Células MCF-7
3.
Int J Biol Macromol ; 256(Pt 2): 128513, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38040159

RESUMO

Nano drug delivery systems offer several benefits, including enhancing drug solubility, regulating drug release, prolonging drug circulation time, and minimized toxicity and side effects. However, upon entering the bloodstream, nanoparticles (NPs) encounter a complex biological environment and get absorbed by various biological components, primarily proteins, leading to the formation of a 'Protein Corona'. The formation of the protein corona is affected by the characteristics of NPs, the physiological environment, and experimental design, which in turn affects of the immunotoxicity, specific recognition, cell uptake, and drug release of NPs. To improve the abundance of a specific protein on NPs, researchers have explored pre-coating, modifying, or wrapping NPs with the cell membrane to reduce protein adsorption. This paper, we have reviewed studies of the protein corona in recent years, summarized the formation and detection methods of the protein corona, the effect of the protein corona composition on the fate of NPs, and the design of new drug delivery systems based on the optimization of protein corona to provide a reference for further study of the protein corona and a theoretical basis for the clinical transformation of NPs.


Assuntos
Nanopartículas , Coroa de Proteína , Coroa de Proteína/metabolismo , Proteínas , Sistemas de Liberação de Medicamentos/métodos , Membrana Celular/metabolismo
4.
Int J Biol Macromol ; 257(Pt 1): 128658, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38065446

RESUMO

Nanodrug delivery systems based on tumor microenvironment responses have shown excellent performance in tumor-targeted therapy, given their unique targeting and drug-release characteristics. Matrix metalloproteinases (MMPs) have been widely explored owing to their high specificity and expression in various tumor microenvironments. The design of an enzyme-sensitive nanodelivery system using MMPs as targeted receptors could markedly improve the performance of drug targeting. The current review focuses on the development and application of MMP-responsive drug carriers, and summarizes the classification of single- and multi-target nanocarriers based on their MMP responsiveness. The potential applications and challenges of this nanodrug delivery system are discussed to provide a reference for designing high-performance nanodrug delivery systems.


Assuntos
Nanopartículas , Neoplasias , Humanos , Sistemas de Liberação de Medicamentos , Portadores de Fármacos/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Sistemas de Liberação de Fármacos por Nanopartículas , Microambiente Tumoral , Metaloproteinases da Matriz
5.
Int J Biol Macromol ; 220: 1133-1145, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-35988724

RESUMO

Efficient drug loading, tumor targeting, intratumoral penetration, and cellular uptake are the main factors affecting the effectiveness of drug delivery systems in oncotherapy. Based on the tumor microenvironment, we proposed to develop Curcumin (Cur)-loaded matrix metalloproteinase (MMP)-responsive nanoparticles (Cur-P-NPs) by static electricity, to enhance tumor targeting, cellular uptake, and drug loading efficiency. These nanoparticles combine the properties of both PEG-peptides (cleaved peptide + penetrating peptide) and star-shaped polyester (DPE-PCL) nanoparticles. Cur-P-NPs displayed good entrapment efficiency, drug loading and biocompatibility. Additionally, they showed an enhanced release rate, cellular uptake, and anti-proliferative activity by activating peptides under the simulated tumor microenvironment. Furthermore, intraperitoneal injection of losartan (LST) successfully enhanced intratumoral drug penetration by collagen I degradation. In vivo studies based on the systematic administration of the synergistic LST + Cur-P-NPs combination to mice confirmed that combined antitumor therapy with LST and Cur-P-NPs could further improve intratumor distribution, enhance anticancer efficacy, and reduce the toxicity and side effects. Therefore, LST + Cur-P-NPs represent a new and efficient system for clinical oncotherapy.


Assuntos
Curcumina , Nanopartículas , Neoplasias , Animais , Linhagem Celular Tumoral , Colágeno , Curcumina/química , Sistemas de Liberação de Medicamentos , Losartan , Metaloproteinases da Matriz/metabolismo , Camundongos , Sistemas de Liberação de Fármacos por Nanopartículas , Nanopartículas/química , Neoplasias/tratamento farmacológico , Tamanho da Partícula , Poliésteres/química , Microambiente Tumoral
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