Conjugated and Entrapped HPMA-PLA Nano-Polymeric Micelles Based Dual Delivery of First Line Anti TB Drugs: Improved and Safe Drug Delivery against Sensitive and Resistant Mycobacterium Tuberculosis

Upadhyay, Seema; Khan, Iliyas; Gothwal, Avinash; Pachouri, Praveen K.; Bhaskar, N.; Gupta, Umesh; Chauhan, D. S.

doi:10.1007/s11095-017-2206-3

Cited by 33 publications

(14 citation statements)

References 24 publications

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“…And due to hydrophobic interaction, it is easily loaded into the hydrophobic core, with high drug solubility [ 20 , 21 ]. Previous research [ 22 ] has shown that the formation of HPMA-PLA-RIF copolymer micelles enhanced the efficacy of drugs, improved the solubility of drugs, and combated the resistance of tuberculostatics. To observe whether HPMA-PLA has toxicity to macrophages, we intervened with infected or uninfected macrophages with HPMA-PLA without drug loading.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Rifampicin Loaded by HPMA-PLA Nanopolymer on Macrophages Infected with Mycobacterium Tuberculosis

Wang

Liu

et al. 2022

Computational and Mathematical Methods in Medicine

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Purpose. This research was designed to investigate the protective effect of rifampicin (RIF) loaded by N-(2-hydroxypropyl) methylacrylamide- (HPMA-) polylactic acid (PLA) nanopolymer on macrophages infected with Mycobacterium tuberculosis (MTB). Methods. We first induced H37Rv to infect macrophages to build a cell model. Then, the HPMA-PLA nanopolymer loaded with RIF was prepared to treat MTB-infected macrophages. The macrophage activity was tested by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the nitric oxide (NO) in cells was measured through Griess reagent, and the bacterial activity of MTB was observed via the colony-forming unit (CFU) assay. The inflammation-related factors in cells were detected via the enzyme-linked immunosorbent assay (ELISA), the apoptosis of macrophages was examined via flow cytometry, and the expression of apoptosis-related proteins was determined by western blot (WB). Results. HPMA-PLA had no obvious toxicity to macrophages. The expression of NO and inflammatory factors in macrophages infected with MTB increased significantly, but the apoptosis rate was not significantly different from that of uninfected cells. However, after treatment with HPMA-PLA-RIF or free RIF, the inflammatory reaction of infected cells was inhibited, the expression of NO was decreased, the apoptosis rate was increased, and the bacterial activity in cells was decreased, with statistically significant differences; moreover, HPMA-PLA-RIF was more effective than free RIF. Conclusions. HPMA-PLA-RIF has a high protective effect on macrophages infected with MTB, with high safety. Its protective mechanism is at least partly through inhibiting the production of NO and inflammatory response, which can inhibit bacterial activity and induce cell apoptosis.

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Section: Discussionmentioning

confidence: 99%

Protective Effect of Rifampicin Loaded by HPMA-PLA Nanopolymer on Macrophages Infected with Mycobacterium Tuberculosis

Wang

Liu

et al. 2022

Computational and Mathematical Methods in Medicine

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“…7−9 For example, these systems enhance the therapeutic effectiveness and minimize the undesirable side effects of numerous antibacterial drugs. 5,10 In this context, several types of anti-TB nanoformulations including for example solid lipid nanoparticles, 7,11 inorganic nanoparticles, 8,12,13 micelles, 14 and polymeric nanoparticles 15−18 have been utilized. In other words, a wide variety of nanocarriers and biomaterials have been explored for mono-and multidrug delivery in TB.…”

Section: ■ Introductionmentioning

confidence: 99%

“…In this context, several types of anti-TB nanoformulations including for example solid lipid nanoparticles, , inorganic nanoparticles, ,, micelles, and polymeric nanoparticles − have been utilized. In other words, a wide variety of nanocarriers and biomaterials have been explored for mono- and multidrug delivery in TB.…”

Section: Introductionmentioning

confidence: 99%

Rifampicin Nanoformulation Enhances Treatment of Tuberculosis in Zebrafish

et al. 2019

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Mycobacterium tuberculosis, the etiologic agent of tuberculosis, is an intracellular pathogen of alveolar macrophages. These cells avidly take up nanoparticles, even without the use of specific targeting ligands, making the use of nanotherapeutics ideal for the treatment of such infections. Methoxy poly(ethylene oxide)-block-poly(ε-caprolactone) nanoparticles of several different polymer blocks’ molecular weights and sizes (20–110 nm) were developed and critically compared as carriers for rifampicin, a cornerstone in tuberculosis therapy. The polymeric nanoparticles’ uptake, consequent organelle targeting and intracellular degradation were shown to be highly dependent on the nanoparticles’ physicochemical properties (the cell uptake half-lives 2.4–21 min, the degradation half-lives 51.6 min–ca. 20 h after the internalization). We show that the nanoparticles are efficiently taken up by macrophages and are able to effectively neutralize the persisting bacilli. Finally, we demonstrate, using a zebrafish model of tuberculosis, that the nanoparticles are well tolerated, have a curative effect, and are significantly more efficient compared to a free form of rifampicin. Hence, these findings demonstrate that this system shows great promise, both in vitro and in vivo, for the treatment of tuberculosis.

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“…Debido a su biocompatibilidad, estabilidad estructural, alta capacidad de transportar medicamentos en su superficie externa y de solubilizar medicamentos hidrofóbicos en su núcleo interno, tienen ventajas sobre otras NP para transportar diversos tipos de fármacos. Detalles sobre la evaluación de estas NP para transportar rifampicina se puede encontrar en la Tabla 5 (45)(46)(47)(48)(49) .…”

Section: Nanomicela (Nmc)unclassified

Nanopartículas como transportadores de fármacos: una herramienta prometedora contra la tuberculosis

Luna-Herrera

Pérez-Martínez

Barradas-Hernández

et al. 2021

Rev Peru Med Exp Salud Publica

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La Organización Mundial de la Salud (OMS) ubica a la tuberculosis (TB) como uno de los problemas de salud más preocupantes en la actualidad, y señala que se requieren de acciones novedosas para controlar su expansión y, de esta manera, alcanzar una de las metas establecidas en los Objetivos de Desarrollo Sostenible: reducir para 2030 la morbilidad e incidencia de TB. Para lograr este objetivo, está claro que las herramientas empleadas actualmente para su diagnóstico y tratamiento ya no son las adecuadas. En este sentido, es necesario desarrollar nuevos medicamentos y vacunas, así como novedosos procedimientos de administración de fármacos que generen una mejor respuesta, disminuyan el tiempo y optimicen los tratamientos. La nanotecnología ha incorporado en los últimos años un gran número de nuevas herramientas que incrementan considerablemente, la diversidad de mecanismos para la administración de tratamientos antituberculosos. Dicho esto, la presente revisión describe brevemente el estado actual de la farmacorresistencia en TB, así como las características generales de las nanopartículas que están evaluándose como herramientas para transportar antibióticos antituberculosos.

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Conjugated and Entrapped HPMA-PLA Nano-Polymeric Micelles Based Dual Delivery of First Line Anti TB Drugs: Improved and Safe Drug Delivery against Sensitive and Resistant Mycobacterium Tuberculosis

Abstract: RIF loaded and INH conjugated HPMA-PLA polymeric micelles (PMRI) were more effective against sensitive and resistant M tuberculosis. The developed approach can lead to improved patient compliance and reduced dosing in future, offering improved treatment of tuberculosis.

Cited by 33 publications

References 24 publications

Protective Effect of Rifampicin Loaded by HPMA-PLA Nanopolymer on Macrophages Infected with Mycobacterium Tuberculosis

Protective Effect of Rifampicin Loaded by HPMA-PLA Nanopolymer on Macrophages Infected with Mycobacterium Tuberculosis

Rifampicin Nanoformulation Enhances Treatment of Tuberculosis in Zebrafish

Nanopartículas como transportadores de fármacos: una herramienta prometedora contra la tuberculosis

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