Etoposide encapsulated in positively charged liposomes: pharmacokinetic studies in mice and formulation stability studies

Sengupta, Shiladitya; Tyagi, Pradeep; Velpandian, Thirumurthy; Gupta, Yogendra Kumar; Gupta, Sudheer

doi:10.1006/phrs.2000.0714

Cited by 44 publications

(37 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As two components of the clinically utilized EDP-M scheme (Fassnacht et al 2012), doxorubicin and cisplatin, are available as sterically stabilized liposomal formulations, we replaced these free agents with their liposomal variants. Although successful liposomal encapsulation has also been described for etoposide (Sengupta et al 2000, Sistla et al 2009 is not yet available as a commercial preparation. The experimental results presented herein confirmed the results of our previous work and theoretical assumptions: short-term therapeutic treatment with LEDP-M led to a significant decrease in the number of Ki67-negative cells and total number of tumor cells in the investigated NCIh295 tumors, while no therapeutic effect was evident in animals treated with the classical EDP-M scheme.…”

Section: Discussionmentioning

confidence: 99%

“…Although successful liposomal encapsulation has also been described for etoposide with reduced volume of distribution and decreased plasma clearance (Sengupta et al 2000, Sistla et al 2009), this formulation is not yet available as a commercial preparation. As doxorubicin and cisplatin have been shown to result in good therapeutic responses together with paclitaxel (Stathopoulos et al 2006, Leonardi et al 2010, we included two further study arms where etoposide was replaced either with conventional paclitaxel (paclitaxel, doxorubicin, cisplatin plus mitotane (PDP-M)) or with a novel nanotechnologically optimized variant of this drug (nab-paclitaxel, LPDP-M (nab-paclitaxel, liposomal doxorubicin, liposomal cisplatin plus mitotane)).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Liposomal polychemotherapy improves adrenocortical carcinoma treatment in a preclinical rodent model

Hantel¹,

Jung²,

Mussack³

et al. 2014

Endocrine-Related Cancer

View full text Add to dashboard Cite

Owing to high relapse rates and early metastatic spread, prognosis in adrenocortical carcinoma (ACC) patients remains poor, highlighting the importance of developing new treatment alternatives for them. Recently, polychemotherapy regimens including etoposide, doxorubicin, and cisplatin together with mitotane (EDP-M) have been defined as the standard treatment for late-stage disease patients. Nevertheless, the administration of conventional cytostatic drugs is associated with severe and dose-limiting side effects. In an attempt to optimize existing clinical treatment regimens, in this study, we investigated the therapeutic efficacy of EDP-M in comparison with that of a paclitaxel-modified scheme (paclitaxel, doxorubicin, cisplatin plus mitotane (PDP-M)) in preclinical in vitro and in vivo models. In addition, based on an extraordinary uptake phenomenon of liposomes in ACC cells, we further evaluated liposomal variants of these protocols (etoposide, liposomal doxorubicin, liposomal cisplatin plus mitotane (LEDP-M) and nab-paclitaxel, liposomal doxorubicin, liposomal cisplatin plus mitotane (LPDP-M)). In vitro, PDP-M was more potent in the induction of apoptosis and inhibition of cell viability as well as cell proliferation than EDP-M. Following the administration of a single therapeutic cycle, we further demonstrated that LEDP-M and LPDP-M exerted significant antitumoral effects in vivo, which were not as evident upon EDP-M and PDP-M treatments. These results were confirmed in a long-term experiment, in which the highest and sustained antitumoral effects were observed for LEDP-M. In summary, liposomal cytostatic substances could represent a promising option that deserves testing in appropriate clinical protocols for the treatment of ACC patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Liposomal polychemotherapy improves adrenocortical carcinoma treatment in a preclinical rodent model

Hantel¹,

Jung²,

Mussack³

et al. 2014

Endocrine-Related Cancer

View full text Add to dashboard Cite

show abstract

“…Our results are in agreement with the above report, and at the same time the blood concentrations were significantly higher for ETP nanoparticles than for ETN nanoparticles. Sengupta and coworkers 40 reported significantly enhanced plasma half-life of etoposide incorporated into cationic liposomes prepared using stearylamine as positively charged lipid. Yu and Lin 41 also reported that the positively charged liposomes resulted in higher plasma-liposome concentration than the negatively charged liposomes.…”

Section: Blood Clearance and Biodistribution Studiesmentioning

confidence: 99%

Etoposide-incorporated tripalmitin nanoparticles with different surface charge: Formulation, characterization, radiolabeling, and biodistribution studies

Reddy

Sharma

Chuttani

et al. 2004

AAPS J

121

View full text Add to dashboard Cite

Etoposide-incorporated tripalmitin nanoparticles with negative (ETN) and positive charge (ETP) were prepared by melt emulsification and high-pressure homogenization techniques. Spray drying of nanoparticles led to free flowing powder with excellent redispersibility. The nanoparticles were characterized by size analysis, zeta potential measurements, and scanning electron microscopy. The mean diameter of ETN and ETP nanoparticles was 391 nm and 362 nm, respectively, and the entrapment efficiency was more than 96%. Radiolabeling of etoposide and nanoparticles was performed with Technetium-99m ( 99m Tc) with high labeling efficiency and in vitro stability. The determination of binding affinity of 99m Tclabeled complexes by diethylene triamine penta acetic acid (DTPA) and cysteine challenge test confirmed low transchelation of 99m Tc-labeled complexes and high in vitro stability. Pharmacokinetic data of radiolabeled etoposide, ETN, and ETP nanoparticles in rats reveal that positively charged nanoparticles had high blood concentrations and prolonged blood residence time. Biodistribution studies of 99m Tc-labeled complexes were performed after intravenous administration in mice. Both ETN and ETP nanoparticles showed significantly lower uptake by organs of the reticuloendothelial system such as liver and spleen (P < .001) compared with etoposide. The ETP nanoparticles showed a relatively high distribution to bone and brain (14-fold higher than etoposide and ETN at 4 hours postinjection) than ETN nanoparticles. The ETP nanoparticles with long circulating property could be a beneficial delivery system for targeting to tumors by Enhanced Permeability and Retention effect and to brain.

show abstract

“…Laverman et al (1999) relataram estudo sobre o efeito do tamanho das vesículas sobre a taxa de remoção de lipossomas de composição lipídica idêntica, variando-se o tamanho (200 e 400 nm). Uma diferença significativa foi observada, visto que os lipossomas grandes foram removidos do sangue mais rapidamente, com tempo de meia-vida (t ½ ) = 0,2 h, comparado com as vesículas menores que apresentaram t ½ = 1,5 h. Sengupta et al (2000) afirmaram que a incorporação de colesterol na formulação de lipossomas carregados positivamente contendo etoposídeo, um agente antineoplásico, aumentou a estabilidade dos lipossomas em soro, constituindo um dos fatores mais importantes na manutenção da integridade da membrana das vesículas e dessa forma prolongando o tempo de circulação in vivo. Lipossomas pobres ou livres de colesterol são predominantemente localizados no fígado após sua administração.…”

Section: Estabilidadeunclassified

Lipossomas e suas aplicações terapêuticas: estado da arte

Batista¹,

Carvalho²,

Magalhães³

2007

Rev. Bras. Cienc. Farm.

View full text Add to dashboard Cite

Lipossomas são vesículas constituídas de uma ou mais bicamadas INTRODUÇÃOAlec Bangham há 40 anos com sua observação pioneira de que fosfolipídeos em soluções aquosas podem formar estruturas fechadas em bicamadas, permitiu que a pesquisa sobre os lipossomas percorresse um longo caminho, convertendo-os de simples objetos de pesquisa biofísica em carreadores terapêuticos para numerosas aplicações clínicas (Torchilin, 2005).Os primeiros resultados das pesquisas foram, entre-

show abstract

Etoposide encapsulated in positively charged liposomes: pharmacokinetic studies in mice and formulation stability studies

Cited by 44 publications

References 15 publications

Liposomal polychemotherapy improves adrenocortical carcinoma treatment in a preclinical rodent model

Liposomal polychemotherapy improves adrenocortical carcinoma treatment in a preclinical rodent model

Etoposide-incorporated tripalmitin nanoparticles with different surface charge: Formulation, characterization, radiolabeling, and biodistribution studies

Lipossomas e suas aplicações terapêuticas: estado da arte

Contact Info

Product

Resources

About