Targeting lipodisks enable selective delivery of anticancer peptides to tumor cells

Ahlgren, Sara; Reijmar, Karin; Edwards, Katarina

doi:10.1016/j.nano.2017.06.020

Cited by 16 publications

(17 citation statements)

References 16 publications

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“…Lipid bilayer disks (lipodisks) are nanosized bilayer structures, stabilized into flat, circular shapes by polyethylene glycol (PEG)-linked lipids [12][13][14]. These nanoparticles show great potential as drug carriers and have been preclinically assessed for delivery of anti-cancer and anti-bacterial compounds [13,[15][16][17][18][19]. Moreover, a targeting moiety can be attached to the lipodisk to increase delivery to desired tissues.…”

Section: Introductionmentioning

confidence: 99%

“…Epidermal growth factor receptor (EGFR) is upregulated in several cancers, and has emerged as a target for diagnostic imaging and therapy [20]. Consequently, we have developed and utilized EGFR-targeted lipodisks for delivery of different classes of anti-cancer drugs [15,19]. In the present study, we investigated the feasibility of delivering the novel p53-activating peptide VIP116 to tumor cells via EGFR-targeted lipodisks.…”

Section: Introductionmentioning

confidence: 99%

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Tumor-Targeted Delivery of the p53-Activating Peptide VIP116 with PEG-Stabilized Lipodisks

et al. 2020

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Stapled peptides targeting the interaction between p53 and its negative regulators MDM2 and MDM4 have exhibited great potential as anti-cancer drugs, albeit with room for improvement in formulation and tumor specificity. Lipid bilayer disks (lipodisks) have emerged as promising drug nanocarriers and can by attachment of targeting moieties be directed selectively towards tumor cells. Tumor-targeted delivery of stapled peptides by use of lipodisks may therefore increase the uptake in the tumors and limit toxicity in healthy tissue. Here, we utilized epidermal growth factor receptor (EGFR)-targeted lipodisks to deliver p53-activating stapled peptide VIP116 to EGFR-expressing tumor cells. We demonstrate that VIP116 can be stably formulated in lipodisks (maximum peptide/lipid molar ratio 0.11). In vitro cell studies verify specific binding of EGF-decorated lipodisks to tumor cells and confirm that targeted delivery of VIP116 significantly decreases tumor cell viability.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tumor-Targeted Delivery of the p53-Activating Peptide VIP116 with PEG-Stabilized Lipodisks

et al. 2020

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“…Lipodisks consist of a disk-like structure where the phospholipids form a flat lipid surface, and the PEG-lipids are located at the highly curved rim (35)(36)(37). Many published results suggest that lipodisks are promising nanocarriers, and the rich contents of PEG may promote improved EE (38)(39)(40)(41). This is the first report adopting microfluidic methods to prepare lipodisk formulations to the best of our knowledge.…”

Section: Introductionmentioning

confidence: 92%

“…Lipodisks have mainly been utilized as biomimetic membranes; however, there has been promising evidence for application in the drug delivery field. Lipodisks have been shown to be biocompatible, increase drug circulation half-life, and increase tumor accumulation (36,40,52). CSA, dexamethasone, curcumin, and acyclovir were encapsulated in lipodisks with the microfluidic system, the NanoAssemblr, utilizing a 0.03 D/L ratio for CSA and acyclovir and a 0.01 D/L ratio for dexamethasone and curcumin.…”

Section: Liposome Vs Lipodiskmentioning

confidence: 99%

A Systematic Approach for Liposome and Lipodisk Preclinical Formulation Development by Microfluidic Technology

Levy¹,

Yu²,

Estevez³

et al. 2021

AAPS J

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Lipid nanoparticles have transformed the drug delivery field enhancing the therapeutic drug performance of small molecules and biologics with several approved drug products. However, in industry, these more complex drug delivery systems such as liposomes require more material and time to develop. Here, we report a liposome and lipodisk decision tree with model compounds of diverse physicochemical properties to understand how to resourcefully optimize encapsulation efficiency (EE) for these lipid-based drug delivery systems. We have identified trends with physicochemical properties such as Log P, where higher Log P compounds such as curcumin were able to efficiently load into the lipid bilayer resulting in high EE with altering the drug/lipid (D/L) ratio. Moderate Log P compounds such as cyclosporine A and dexamethasone had significantly higher encapsulation in lipodisks, which contain higher amounts of PEG lipid compared to liposomes. The EE of negative Log P compounds, like acyclovir, remained low regardless of altering the D/L ratio and PEG concentrations. In this study, microfluidic techniques were employed to fabricate liposomes and lipodisks formulations allowing for a reproducible strategy for formulation development. Both liposome and lipodisk of curcumin demonstrated enhanced in vivo performance compared with a conventional formulation in the rat pharmacokinetic study. This combination of approaches with multiple model compounds and lipid-based drug delivery systems provides a systematic guidance to effective strategies to generate higher EE with minimal drug waste and expedite the process for preclinical development when applied to industry compounds.

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“…Previous studies showed that a formulation in lipodisks can be used as a viable means to increase tumor accumulation and reduce off-target toxicity of both the anticancer peptide melittin and chemotherapeutic drugs, such as doxorubicin and paclitaxel [149]. Recent results from the Edwards lab showed that by decorating the lipodisks with ligands that recognize selected cell membrane receptors, it is possible to design systems capable of specific tumor cell targeting and true intracellular delivery of both conventional and peptide-based anticancer drugs [150][151][152]. In this project by Edwards, the possibilities to use lipodisks for the co-delivery of chemotherapeutic drugs and membranolytic anticancer peptides will be investigated.…”

Section: Ongoingmentioning

confidence: 99%

The Phospholipid Research Center: Current Research in Phospholipids and Their Use in Drug Delivery

Drescher

Hoogevest

2020

Pharmaceutics

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This review summarizes the research on phospholipids and their use for drug delivery related to the Phospholipid Research Center Heidelberg (PRC). The focus is on projects that have been approved by the PRC since 2017 and are currently still ongoing or have recently been completed. The different projects cover all facets of phospholipid research, from basic to applied research, including the use of phospholipids in different administration forms such as liposomes, mixed micelles, emulsions, and extrudates, up to industrial application-oriented research. These projects also include all routes of administration, namely parenteral, oral, and topical. With this review we would like to highlight possible future research directions, including a short introduction into the world of phospholipids.

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Targeting lipodisks enable selective delivery of anticancer peptides to tumor cells

Cited by 16 publications

References 16 publications

Tumor-Targeted Delivery of the p53-Activating Peptide VIP116 with PEG-Stabilized Lipodisks

Tumor-Targeted Delivery of the p53-Activating Peptide VIP116 with PEG-Stabilized Lipodisks

A Systematic Approach for Liposome and Lipodisk Preclinical Formulation Development by Microfluidic Technology

The Phospholipid Research Center: Current Research in Phospholipids and Their Use in Drug Delivery

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