Stealth monensin liposomes as a potentiator of adriamycin in cancer treatment

Singh, Mandip; Ferdous, Afia; Jackson, Tanise

doi:10.1016/s0168-3659(98)00174-6

Cited by 26 publications

(23 citation statements)

References 26 publications

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“…The observed cytotoxicity with Cxb-NLC formulation was mainly because of i) the Cxb was released in controlled manner for prolonged period of time and/or ii) possibly due to cell internalization of nanoparticles over period of time. Our previous studies with monensin liposome formulation demonstrated that cell internalization of liposomes was time dependent and the particles were endocytosed slowly [31]. …”

Section: Resultsmentioning

confidence: 99%

Formulation, characterization and pulmonary deposition of nebulized celecoxib encapsulated nanostructured lipid carriers

Patlolla

Chougule

Patel

et al. 2010

Journal of Controlled Release

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216

101

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The aim of the current study was to encapsulate celecoxib (Cxb) in the Nanostructured Lipid Carrier (Cxb-NLC) nanoparticles and evaluate the lung disposition of nanoparticles following nebulization in Balb/c mice. Cxb-NLC nanoparticles were prepared with Cxb, Compritol, Miglyol and sodium taurocholate using high-pressure homogenization. Cxb-NLC nanoparticles were characterized for physical and aerosol properties. In-vitro cytotoxicity studies were performed with A549 cells. The lung deposition and pharmacokinetic parameters of Cxb-NLC and Cxb solution (Cxb-Soln) formulations were determined using Inexpose™ system and Pari LC star jet nebulizer. The particle size and entrapment efficiency of Cxb-NLC formulation were 217 ± 20 nm and > 90%, respectively. The Cxb-NLC released the drug in controlled fashion, and in vitro aersolization of Cxb-NLC formulation showed FPF of 75.6 ± 4.6 %, MMAD of 1.6 ±0.13 μm and GSD of 1.2 ± 0.21. Cxb-NLC showed dose and time dependent cytotoxicity against A549 cells. Nebulization of Cxb-NLC demonstrated 4 fold higher AUC t/ D in lung tissues compared to Cxb-Soln. The systemic clearance of Cxb-NLC was slower (0.93 L/h) compared to Cxb-Soln (20.03 L/h). Cxb encapsulated NLC were found to be stable and aerodynamic properties were within the respirable limits. Aerosolization of Cxb-NLC improved the Cxb pulmonary bioavailability compared to solution formulation which will potentially lead to better patient compliance with minimal dosing intervals.

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Section: Resultsmentioning

confidence: 99%

Formulation, characterization and pulmonary deposition of nebulized celecoxib encapsulated nanostructured lipid carriers

Patlolla

Chougule

Patel

et al. 2010

Journal of Controlled Release

Self Cite

216

101

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show abstract

“…poultry industry as feed additive, and lysosomal inhibitors have already been proposed as possible potent antimalarial therapeutics (Gumila et al, 1997) and also been considered as anticancer drugs (Singh et al, 1999;Park et al, 2002). However, monensin has been characterized by a narrow safety margin and may cause lethal toxicoses, especially when coadministered with other drugs (Nebbia et al, 1999).…”

Section: Hepatic Disposition Of Basic Drugs 233mentioning

confidence: 99%

Ion-Trapping, Microsomal Binding, and Unbound Drug Distribution in the Hepatic Retention of Basic Drugs

Siebert¹,

Hung²,

Chang³

et al. 2003

J Pharmacol Exp Ther

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This study investigated the relative contribution of ion-trapping, microsomal binding, and distribution of unbound drug as determinants in the hepatic retention of basic drugs in the isolated perfused rat liver. The ionophore monensin was used to abolish the vesicular proton gradient and thus allow an estimation of ion-trapping by acidic hepatic vesicles of cationic drugs. In vitro microsomal studies were used to independently estimate microsomal binding and metabolism. Hepatic vesicular ion-trapping, intrinsic elimination clearance, permeability-surface area product, and intracellular binding were derived using a physiologically based pharmacokinetic model. Modeling showed that the ion-trapping was significantly lower after monensin treatment for atenolol and propranolol, but not for antipyrine. However, no changes induced by monensin treatment were observed in intrinsic clearance, permeability, or binding for the three model drugs. Monensin did not affect binding or metabolic activity in vitro for the drugs. The observed ion-trapping was similar to theoretical values estimated using the pHs and fractional volumes of the acidic vesicles and the pK a values of drugs. Lipophilicity and pK a determined hepatic drug retention: a drug with low pK a and low lipophilicity (e.g., antipyrine) distributes as unbound drug, a drug with high pK a and low lipophilicity (e.g., atenolol) by ion-trapping, and a drug with a high pK a and high lipophilicity (e.g., propranolol) is retained by ion-trapping and intracellular binding. In conclusion, monensin inhibits the ion-trapping of high pK a basic drugs, leading to a reduction in hepatic retention but with no effect on hepatic drug extraction.Basic lipophilic compounds are characterized by a high volume of distribution as a result of extensive tissue uptake. The main mechanisms of such a distribution pattern are nonspecific binding to membrane phospholipids (Bickel and Steele, 1974;Francesco and Bickel, 1977;Romer and Bickel, 1979), binding to microsomal protein (Hung et al., 2002), and the sequestration of the compounds into acidic vesicular compartments such as lysosomes or mitochondria (Daniel et al., 1995). A potential consequence of an apparent irreversible sequestration of basic drugs into acidic vesicles is a potentially reduced drug bioavailability (de Duve et al., 1974;Ohkuma and Poole, 1978) or drug interactions (Daniel and Wojcikowski, 1999b;Nebbia et al., 1999). Lysosomal trapping of basic lipophilic drugs has also been demonstrated to be an important determinant of disposition for desipramine and chloroquine and psychotropic compounds such as the piperidine and piperazine-type neuroleptics (Daniel et al., 2001). The lysosomotropic properties of basic drugs are particularly important determining drug disposition and pharmacokinetics in lysosome-rich organs such as lungs, kidneys, or the liver.Specific studies determining the relative contribution of ion-trapping and microsomal binding to the hepatic retention of drugs or relating the relative uptake to the ph...

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“…VER and/or liposome activating P-gp leading to modulation of caspase activation with initiation of cell death process. 37,38) Although the primary mechanism of action of DOX is inhibition of topoisomerise-II enzyme function, 39) liposomes could have caused dilatation of the Golgi apparatus and changed the efflux of various proteins 40) or affected other subcellular targets to cause cytotoxicity. DARSLs might have affected the P53 gene to arrest the cells at the G1 phase before apoptosis.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Cytotoxicity of Stealth Liposomes Co-encapsulating Doxorubicin and Verapamil on Doxorubicin-Resistant Tumor Cells

Wang

Goh

et al. 2005

Biological & Pharmaceutical Bulletin

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Stealth monensin liposomes as a potentiator of adriamycin in cancer treatment

Cited by 26 publications

References 26 publications

Formulation, characterization and pulmonary deposition of nebulized celecoxib encapsulated nanostructured lipid carriers

Formulation, characterization and pulmonary deposition of nebulized celecoxib encapsulated nanostructured lipid carriers

Ion-Trapping, Microsomal Binding, and Unbound Drug Distribution in the Hepatic Retention of Basic Drugs

In Vitro Cytotoxicity of Stealth Liposomes Co-encapsulating Doxorubicin and Verapamil on Doxorubicin-Resistant Tumor Cells

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