Ligand-targeted liposome design: challenges and fundamental considerations

Noble, Gavin T.; Stefanick, Jared F.; Ashley, Jonathan D.; Kiziltepe, Tanyel; Bilgiçer, Başar

doi:10.1016/j.tibtech.2013.09.007

Cited by 440 publications

(294 citation statements)

References 114 publications

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“…Although current combination therapies are effective, controlling the drug ratio at the tumor is extremely difficult due to differences in the pharmacokinetics, biodistribution, and metabolism of each drug (5-7). Nanotechnology can overcome these problems by loading the therapeutics into nanoparticles at the optimal ratio to facilitate their controlled release and increase their accumulation in the tumor due to the EPR effect enabled by angiogenic blood vessels (12,31). Recent studies have established that angiogenesis plays a critical role in various hematologic malignancies including multiple myeloma, providing a strong rationale to exploit nanotechnology in managing this disease (33,34).…”

Section: Discussionmentioning

confidence: 99%

“…This was also consistent with non-drug-loaded liposomes, showing that the presence of the therapeutics does not affect the size of the liposomes. Importantly, the diameter of these liposomes falls within the particle size range required for the passive targeting of tumors via the enhanced permeability and retention (EPR) effect (12,31).…”

Section: Preparation Of Carfilzomib and Doxorubicin-loaded Liposomal mentioning

confidence: 99%

“…Although this will not accurately represent MTD for NP [carfþdox], it can still be used to set the dosing parameters for comparison studies, as we expect the nanoparticle formulations to be less toxic relative to the free drug formulations (5,9,12). SCID mice were subcutaneously injected with NCI-H929 cells.…”

Section: Determination Of the Mtd For The Free Carfilzomib And Free Dmentioning

confidence: 99%

“…6B). We anticipate that the increased efficacy of NP[carfþdox] over carf þ dox was due to the delivery of the drugs at their optimal ratio as well as the other advantages gained from nanoparticle incorporation (10,12).…”

Section: In Vivo Efficacy Of the Dual Drug-loaded Liposomesmentioning

confidence: 99%

“…PEGylated liposomal nanoparticles are attractive drug delivery vehicles for the significant advantages they possess over other nanoparticle types, such as high drug-loading capabilities, facile incorporation of different functionalities, improved biocompatibility, and precise control over particle size (9,12). In addition, it is possible to incorporate drugs with various physiochemical properties in the different compartments of liposomes.…”

Section: Introductionmentioning

confidence: 99%

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Dual Carfilzomib and Doxorubicin–Loaded Liposomal Nanoparticles for Synergistic Efficacy in Multiple Myeloma

Ashley

Quinlan

Schroeder

et al. 2016

Molecular Cancer Therapeutics

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Here, we report the synthesis and evaluation of dual drugloaded nanoparticles as an effective means to deliver carfilzomib and doxorubicin to multiple myeloma tumor cells at their optimal synergistic ratio. First, various molar ratios of carfilzomib to doxorubicin were screened against multiple myeloma cell lines to determine the molar ratio that elicited the greatest synergy using the Chou-Talalay method. The therapeutic agents were then incorporated into liposomes at the optimal synergistic ratio of 1:1 to yield dual drug-loaded nanoparticles with a narrow size range of 115 nm and high reproducibility. Our results demonstrated that the dual drug-loaded liposomes exhibited synergy in vitro and were more efficacious in inhibiting tumor growth in vivo than a combination of free drugs, while at the same time reducing systemic toxicity. Taken together, this study presents the synthesis and preclinical evaluation of dual drug-loaded liposomes containing carfilzomib and doxorubicin for enhanced therapeutic efficacy to improve patient outcome in multiple myeloma.

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