Advances in Targeting Drug Delivery to Glomerular Mesangial Cells by Long Circulating Cationic Liposomes for the Treatment of Glomerulonephritis

Morimoto, Katsumi; Kondo, Masayo; Kawahara, Kazuo; Ushijima, Hideto; Tomino, Yasuhiko; Miyajima, Masaharu; Kimura, Junji

doi:10.1007/s11095-006-9213-0

Cited by 35 publications

(22 citation statements)

References 21 publications

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“…16,17 The appearance of the signals from the three aromatic protons of the amidine group at ppm 7.80 and 9.80 in the 1 H-NMR spectra indicated the successful synthesis of TRX-20.…”

Section: Results and Discussion Synthesis And Cytotoxicity Of Trx-20mentioning

confidence: 99%

“…[30][31][32] Consistent with Zhou's report, the high levels of NO and TNF-α released by the LPS-stimulated MCs were effectively attenuated by co-incubation with TP for 24 h ( Figure 5). TRX-20 has a high affinity for MCs, 16 and this specificity was exploited in this study to develop renal-targeted therapy of TP. Pegylation of the resultant TRX-TP-LP was also utilized as a means to improve therapeutic efficiency in vivo.…”

Section: Anti-inflammatory Activity Of Trx-tp-lp and Peg-trx-tp-lpmentioning

confidence: 99%

“…PEGylation can prolong blood circulation time of the liposomes and allowed them to accumulate in targeting tissues where the liposomes repeatedly pass by. The final liposomes have diameter of around 100 nm, 16 positive zeta potential, and high selection for MCs over vascular endothelial cells. 17 It is clear that MCs as an effective target site are adopted in all the studies mentioned above.…”

mentioning

confidence: 99%

“…15,16 It is also worth noting that the anti-inflammatory activity of TP was elicited by applying TRX-TP-LP and PEG-TRX-TP-LP at equivalent total lipid concentration of lower than 0.05 mg/mL, which was 22.6 times lower than the IC 50 of 11%-TRX-LP, and at which the viability of MCs was 96.51% (Figure 2). …”

mentioning

confidence: 99%

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Renal-targeted delivery of triptolide by entrapment in pegylated TRX-20-modified liposomes

Yuan

Jia

Lim

et al. 2017

IJN

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Previously, 3,5-dipentadecyloxybenzamidine hydrochloride (TRX-20)-modified liposomes were reported to specifically target mesangial cells (MCs) in glomeruli. To further gain a better understanding of the characteristics and potential application for glomerular diseases of TRX-20-modified liposomes, we synthesized TRX-20 and prepared TRX-20-modified liposomes (TRX-LPs) with different molar ratios – 6% (6%-TRX-LP), 11% (11%-TRX-LP), and 14% (14%-TRX-LP) – of TRX-20 to total lipid in the present study. All TRX-LPs exhibited concentration-dependent toxicity against the MCs at a lipid concentration ranging from 0.01 to 1.0 mg/mL with IC 50 values of 3.45, 1.13, and 0.55 mg/mL, respectively. Comparison of the cell viability of TRX-LPs indicated that high levels of TRX-20 caused severe cell mortality, with 11%-TRX-LP showing the higher cytoplasmic accumulation in the MCs. Triptolide (TP) as a model drug was first loaded into 11%-TRX-LP and the liposomes were further modified with PEG 5000 (PEG-TRX-TP-LP) in an attempt to prolong their circulation in blood and enhance TP-mediated immune suppression. Due to specific binding to MCs, PEG-TRX-TP-LP undoubtedly showed better anti-inflammatory action in vitro, evidenced by the inhibition of release of nitric oxide (NO) and tumor necrosis factor-α from lipopolysaccharide-stimulated MCs, compared with free TP at the same dose. In vivo, the PEG-TRX-TP-LP effectively attenuated the symptoms of membranous nephropathic (MN) rats and improved biochemical markers including proteinuria, serum cholesterol, and albumin. Therefore, it can be concluded that the TRX-modified liposome is an effective platform to target the delivery of TP to glomeruli for the treatment of MN.

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“…16,17 The appearance of the signals from the three aromatic protons of the amidine group at ppm 7.80 and 9.80 in the 1 H-NMR spectra indicated the successful synthesis of TRX-20.…”

Section: Results and Discussion Synthesis And Cytotoxicity Of Trx-20mentioning

confidence: 99%

Section: Anti-inflammatory Activity Of Trx-tp-lp and Peg-trx-tp-lpmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Renal-targeted delivery of triptolide by entrapment in pegylated TRX-20-modified liposomes

Yuan

Jia

Lim

et al. 2017

IJN

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“…According to the physicochemical characteristics of the phospholipid membrane, liposome is a most hopeful nano-carrier with the opportunity to offer targeting therapy, thus increases the quality of cancer patient care (Ono et al, 2002;Morimoto et al, 2007;Asai et al, 2008;Abu Lila et al, 2009). So far, several liposomal drugs have already been authorized to treat cancer.…”

Section: Introductionmentioning

confidence: 99%

Preparation, characterization, and efficacy of thermosensitive liposomes containing paclitaxel

Wang¹,

Zhang²,

Yang³

et al. 2015

Drug Delivery

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To increase the anti-tumor activity of paclitaxel (PTX), novel temperature-sensitive liposomes loading paclitaxel (PTX-TSL) were developed. In vitro, characteristics of PTX-TSL were evaluated. The mean particle diameter was about 100 nm, and the entrapment efficiency was larger than 95%. The phase-transition temperature of PTX-TSL determined by differential scanning calorimetry was about 42C. The result of in vitro drug release from PTX-TSL illustrated that release rate at 37 C was obviously lower than that at 42 C. Stability data indicated that the liposome was physically and chemically stable for at least 3 months at À20 C. In vivo study, after three injections with hyperthermia in the xenograft lung tumor model, PTX-TSL showed distinguished tumor growth suppression, compared with non-temperature-sensitive liposome and free drug. The results of intratumoral drug concentration indicated that PTX-TSL combined with hyperthermia delivered more paxlitaxel into the tumor location than the other two paxlitaxel formulations. In summary, PTX-TSL combined with hyperthermia significantly inhibited tumor growth, due to the increased targeting efficiency of PTX to tumor tissues. Such approach may enhance the delivery efficiency of chemotherapeutics into solid tumors.

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Nanoparticles Mimicking Viral Cell Recognition Strategies Are Superior Transporters into Mesangial Cells

et al. 2020

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Poor drug availability in the tissue of interest is a frequent cause of therapy failure. While nanotechnology has developed a plethora of nanocarriers for drug transport, their ability to unequivocally identify cells of interest remains moderate. Viruses are the ideal nanosized carriers as they are able to address their embedded nucleic acids with high specificity to their host cells. Here, it is reported that particles endowed with a virus‐like ability to identify cells by three consecutive checks have a superior ability to recognize mesangial cells (MCs) in vivo compared to conventional nanoparticles. Mimicking the initial viral attachment followed by a stepwise target cell recognition process leads to a 5‐ to 15‐fold higher accumulation in the kidney mesangium and extensive cell uptake compared to particles lacking one or both of the viral traits. These results highlight the relevance that the viral cell identification process has on specificity and its application on the targeting strategies of nanomaterials. More so, these findings pave the way for transporting drugs into the mesangium, a tissue that is pivotal in the development of diabetic nephropathy and for which currently no efficient pharmacotherapy exists.

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Advances in Targeting Drug Delivery to Glomerular Mesangial Cells by Long Circulating Cationic Liposomes for the Treatment of Glomerulonephritis

Abstract: The pharmaceutical properties of TRX-liposomes due to their preferential binding to mesangial cells and long circulation time make this a likely candidate system for targeted drug delivery to the inflamed glomeruli of glomerulonephritis.

Cited by 35 publications

References 21 publications

Renal-targeted delivery of triptolide by entrapment in pegylated TRX-20-modified liposomes

Renal-targeted delivery of triptolide by entrapment in pegylated TRX-20-modified liposomes

Preparation, characterization, and efficacy of thermosensitive liposomes containing paclitaxel

Nanoparticles Mimicking Viral Cell Recognition Strategies Are Superior Transporters into Mesangial Cells

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