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1.
Mol Pharm ; 21(5): 2238-2249, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38622497

RESUMO

Tuberculosis (TB) is a chronic disease caused byMycobacterium tuberculosis (Mtb), which shows a long treatment cycle often leads to drug resistance, making treatment more difficult. Immunogens present in the pathogen's cell membrane can stimulate endogenous immune responses. Therefore, an effective lipid-based vaccine or drug delivery vehicle formulated from the pathogen's cell membrane can improve treatment outcomes. Herein, we extracted and characterized lipids fromMycobacterium smegmatis, and the extracts contained lipids belonging to numerous lipid classes and compounds typically found associated with mycobacteria. The extracted lipids were used to formulate biomimetic lipid reconstituted nanoparticles (LrNs) and LrNs-coated poly(lactic-co-glycolic acid) nanoparticles (PLGA-LrNs). Physiochemical characterization and results of morphology suggested that PLGA-LrNs exhibited enhanced stability compared with LrNs. And both of these two types of nanoparticles inhibited the growth of M. smegmatis. After loading different drugs, PLGA-LrNs containing berberine or coptisine strongly and synergistically prevented the growth of M. smegmatis. Altogether, the bacterial membrane lipids we extracted with antibacterial activity can be used as nanocarrier coating for synergistic antibacterial treatment of M. smegmatis─an alternative model of Mtb, which is expected as a novel therapeutic system for TB treatment.


Assuntos
Mycobacterium smegmatis , Nanopartículas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Nanopartículas/química , Mycobacterium smegmatis/efeitos dos fármacos , Lipídeos/química , Sinergismo Farmacológico , Membrana Celular/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/efeitos dos fármacos , Antituberculosos/farmacologia , Antituberculosos/química , Antituberculosos/administração & dosagem , Mycobacterium/efeitos dos fármacos , Berberina/farmacologia , Berberina/química , Portadores de Fármacos/química , Tuberculose/tratamento farmacológico
2.
Pharmacol Res ; 199: 107022, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38043691

RESUMO

Macrophages, as highly phenotypic plastic immune cells, play diverse roles in different pathological conditions. Changing and controlling the phenotypes of macrophages is considered a novel potential therapeutic intervention. Meanwhile, specific transmembrane proteins anchoring on the surface of the macrophage membrane are relatively conserved, supporting its functional properties, such as inflammatory chemotaxis and tumor targeting. Thus, a series of drug delivery systems related to specific macrophage membrane proteins are commonly used to treat chronic inflammatory diseases. This review summarizes macrophages-based strategies for chronic diseases, discusses the regulation of macrophage phenotypes and their polarization processes, and presents how to design and apply the site-specific targeted drug delivery systems in vivo based on the macrophages and their derived membrane receptors. It aims to provide a better understanding of macrophages in immunoregulation and proposes macrophages-based targeted therapeutic approaches for chronic diseases.


Assuntos
Sistemas de Liberação de Medicamentos , Neoplasias , Humanos , Fenótipo , Macrófagos/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Doença Crônica
3.
Molecules ; 24(19)2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31575047

RESUMO

Large mesopores of chiral silica nanoparticles applied as drug carrier are worth studying. In this study, chiral mesoporous silica nanoparticles (CMSN) and enlarged chiral mesoporous silica nanoparticles (E-CMSN) with a particle size from 200 to 300 nm were synthesized. Fourier transform infrared spectrometer (FTIR), circular dichroism spectrum, scanning electron microscopy (SEM), transmission electron microscope (TEM), and nitrogen adsorption/desorption measurement were adopted to explore their characteristics. The results showed that the surface area, pore volume, and pore diameter of E-CMSN were higher than those of CMSN due to enlarged mesopores. Poorly water-soluble drug nimesulide (NMS) was taken as the model drug and loaded into carriers using adsorption method. After NMS was loaded into CMSN and E-CMSN, most crystalline NMS converted to amorphous phase and E-CMSN was superior. The anti-inflammatory pharmacodynamics and in vivo pharmacokinetics results were consistent with the wetting property and in vitro drug dissolution results, verifying that NMS/E-CMSN exhibited superior NMS delivery system based on its higher oral relative bioavailability and anti-inflammatory effect because its enlarge mesopores contributed to load and release more amorphous NMS. The minor variations in the synthesis process contributed to optimize the chiral nano-silica drug delivery system.


Assuntos
Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Dióxido de Silício/química , Água/química , Adsorção , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacocinética , Liberação Controlada de Fármacos , Camundongos , Nanopartículas/ultraestrutura , Nitrogênio/química , Tamanho da Partícula , Porosidade , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
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