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

Wang, Jian Cheng; Goh, Boon Cher; Lu, Wan Liang; Zhang, Qiang; Chang, Alex Chia Yu; Liu, Xiao Yan; Tan, Thiam Soon; Lee, How Sung

doi:10.1248/bpb.28.822

Cited by 67 publications

(28 citation statements)

References 33 publications

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“…These vesicles then undergo a complex series of fusion events directing the internalized cargo to an appropriate intracellular compartment (uptake of fluids, macromolecules, particles and other ligands that sort to cellular processing pathways). Intracellular uptake studies have largely focused on liposome (75)(76)(77) and polymer delivery systems (20,78,79). Kinetically, three specific modes of endocytosis have been implicated in the context of delivery systems: fluid-phase, adsorptive, and receptor-mediated endocytosis (80).…”

Section: Modes Of Pec and Nanoparticle Internalizationmentioning

confidence: 99%

“…Several PEC systems (77,100,108,(114)(115)(116) have incorporated proteins and analyzed their release kinetics and entrapment. PECs allow the loading of proteins by polyion coacervation between charged groups.…”

Section: Pec Protein Entrapment and Releasementioning

confidence: 99%

“…There are many approaches to stabilize AF750 PECs against opsonization. One strategy would be to enshroud the PECs within a protective layer of hydrophilic polymers, such as PEG (77), in addition to the Pluronic F-68 already present. The surface modifications can be accomplished by activated linkages to sufficiently Fcoat_ the PECs, avoid phagocyte-mediated clearance, increase the circulatory time, and enhance complex stability.…”

Section: Real Time Fluorescent Pec Imagingmentioning

confidence: 99%

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Multifunctional Nanoparticulate Polyelectrolyte Complexes

et al. 2007

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Water-soluble, biodegradable, polymeric, polyelectrolyte complex dispersions (PECs) have evolved because of the limitations, in terms of toxicity, of the currently available systems. These aqueous nanoparticulate architectures offer a significant advantage for products that may be used as drug delivery systems in humans. PECs are created by mixing oppositely charged polyions. Their hydrodynamic diameter, surface charge, and polydispersity are highly dependent on concentration, ionic strength, pH, and molecular parameters of the polymers that are used. In particular, the complexation between polyelectrolytes with significantly different molecular weights leads to the formation of water-insoluble aggregates. Several PEC characteristics are favorable for cellular uptake and colloidal stability, including hydrodynamic diameter less than 200 nm, surface charge of >30 mV or <-30 mV, spherical morphology, and polydispersity index (PDI) indicative of a homogeneous distribution. Maintenance of these properties is critical for a successful delivery vehicle. This review focuses on the development and potential applications of PECs as multi-functional, site-specific nanoparticulate drug/gene delivery and imaging devices.

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Section: Modes Of Pec and Nanoparticle Internalizationmentioning

confidence: 99%

Section: Pec Protein Entrapment and Releasementioning

confidence: 99%

Section: Real Time Fluorescent Pec Imagingmentioning

confidence: 99%

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Multifunctional Nanoparticulate Polyelectrolyte Complexes

et al. 2007

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“…Recently, a novel liposomal formulation containing co-loaded doxorubicin (DOX) and verapamil was synthesized and shown to overcome MDR (23,24). The chemosensitizer verapamil chosen in this study, however, was non-specific for P-gp and would cause side effect.…”

Section: Introductionmentioning

confidence: 99%

Co-delivery of Doxorubicin and PSC 833 (Valspodar) by Stealth Nanoliposomes for Efficient Overcoming of Multidrug Resistance

et al. 2012

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-Purpose. This study was aimed at developing co-encapsulated stealth nanoliposomes containing PSC 833, an efficient MDR modulator, and doxorubicin (DOX) in order to increase the effectiveness and decrease adverse effects of the anticancer drug. Methods. In attempt to increase the encapsulation efficiency of drugs, different methods for liposome preparation were tested and the effect of different parameters such as drug to lipid molar ratio, cholesterol mole percent and lipid compositions, were investigated. The final product with a lipid composition of EPC:DSPE-PEG2000:Chol (60:5:30 %mol) was prepared by thin layer film hydration method. After preparation of empty liposomes, DOX and PSC 833 were loaded using ammonium sulfate gradient and remote film loading methods, respectively. Physical characteristics of optimized liposomes (DOX/PSC-L) such as particle size, zeta potential, encapsulation efficiency, in-vitro drugs release and stability were evaluated. Furthermore, in vitro cytotoxicity study of various liposomal formulations as well as drugs, solutions against resistant human breast cancer cell line, T47D/TAMR-6, was evaluated using MTT assay. Results. The best formulation showed a narrow size distribution with average diameter of 91.3 ± 0.2 nm with zeta potential of -6 ± 1.2, the encapsulation efficiency for DOX and PSC 833 were more than 95% and 65.5%, respectively. In DOX-resistant T47D/TAMR-6 cells, dual-agent stealth liposomes showed significantly greater cytotoxicity (P < 0.05) than free DOX and liposomal DOX plus free PSC 833 treatments. Conclusions. Co-encapsulation of DOX and PSC 833 presents a promising anticancer formulation, capable of effective reversal of drug resistance, and should be explored further in therapeutic studies with animal tumor xenograft models.

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“…This concept has been elegantly shown by Mayer et al (9) in studying combinations of irinotecan/fluoxuridine, daunorubicin/cytarabine, and cisplatin/daunorubicin. In other studies, coencapsulated doxorubicin and verapamil was shown to be highly effective against cells that are multidrug resistant (11). It is conceivable such studies will yield many promising drug combinations with clinical potential.…”

mentioning

confidence: 99%

Liposomal delivery as a mechanism to enhance synergism between anticancer drugs

Lee

2006

Molecular Cancer Therapeutics

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

Cited by 67 publications

References 33 publications

Multifunctional Nanoparticulate Polyelectrolyte Complexes

Multifunctional Nanoparticulate Polyelectrolyte Complexes

Co-delivery of Doxorubicin and PSC 833 (Valspodar) by Stealth Nanoliposomes for Efficient Overcoming of Multidrug Resistance

Liposomal delivery as a mechanism to enhance synergism between anticancer drugs

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