Advances in Tumor Targeted Liposomes

Jain, Ankit; Jain,

doi:10.2174/1566524018666180416101522

Cited by 60 publications

(18 citation statements)

References 127 publications

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“…Active Targeting Approaches. Nanoparticles can be modified with small molecules, peptides, monoclonal antibodies, or antibody fragments to target tumor cells (Fernandes et al, 2015;Jain and Jain, 2018). A wide variety of ligands had been explored in the past to facilitate the tumor-specific uptake of liposomes.…”

Section: Design Considerations In Anticancer Therapymentioning

confidence: 99%

Liposomal Nanostructures for Drug Delivery in Gastrointestinal Cancers

Das

Huang

2018

J Pharmacol Exp Ther

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Gastrointestinal (GI) cancers like liver, pancreatic, colorectal, and gastric cancer remain some of the most difficult and aggressive cancers. Nanoparticles like liposomes had been approved in the clinic for cancer therapy dating as far back as 1995. Over the years, liposomal formulations have come a long way, facing several roadblocks and failures, and advancing by optimizing formulations and incorporating novel design approaches to navigate therapeutic delivery challenges. The first liposomal formulation for a GI cancer drug was approved recently in 2015, setting the stage for further clinical developments of liposomebased delivery systems for therapies against GI malignancies. This article reviews the design considerations and strategies that can be used to deliver drugs to GI tumors, the wide range of therapeutic agents that have been explored in preclinical as well as clinical studies, and the current therapies that are being investigated in the clinic against GI malignancies. This work is supported by the National Institutes of Health [Grant CA198999]. L.H. is a cofounder of OncoTrap, Inc. No other potential conflicts of interest relevant to this article are reported.

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Section: Design Considerations In Anticancer Therapymentioning

confidence: 99%

Liposomal Nanostructures for Drug Delivery in Gastrointestinal Cancers

Das

Huang

2018

J Pharmacol Exp Ther

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“…The surface of the liposomes can be grafted with polyethylene glycols in order to prolong the circulating half-lives of drugs, which, in turn, results in significantly higher accumulation of liposomal drugs in tumors compared to normal tissues via enhanced permeability and retention (EPR) effect 31. Decorating the liposome surface with a tumor-targeting ligand also improves the tumor-specific accumulation, albeit in a more active manner 32. Consequently, liposomal drug formulations elicit considerably less drug-induced toxicity 33.…”

Section: Introductionmentioning

confidence: 99%

<p>Co-delivery of everolimus and vinorelbine via a tumor-targeted liposomal formulation inhibits tumor growth and metastasis in RCC</p>

Pal¹,

Madamsetty²,

Dutta³

et al. 2019

IJN

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Background: Renal cell carcinoma (RCC) is notorious for its resistance towards chemotherapy and radiation therapy in general. Combination therapy is often helpful in alleviating the resistance mechanisms by targeting multiple signaling pathways but is usually more toxic than monotherapy. Co-encapsulation of multiple therapeutic agents in a tumor-targeted drug delivery platform is a promising strategy to mitigate these limitations. Methods: A tumor-targeted liposomal formulation was prepared using phospholipids, cholesterol, DSPE-(PEG) 2000 -OMe and a proprietary tumor-targeting-peptide (TTP)-conjugated lipopeptide. An efficient method was optimized to encapsulate everolimus and vinorelbine in this liposomal formulation. Single drug-loaded liposomes were also prepared for comparison. Finally, the drug-loaded liposomes were tested in vitro and in vivo in two different RCC cell lines. Results: The tumor-targeted liposomal formulation demonstrated excellent tumor-specific uptake. The dual drug-loaded liposomes exhibited significantly higher growth inhibition in vitro compared to the single drug-loaded liposomes in two different RCC cell lines. Similarly, the dual drug-loaded liposomes demonstrated significantly higher suppression of tumor growth compared to the single drug-loaded liposomes in two different subcutaneous RCC xenografts. In addition, the dual drug-loaded liposomes instigated significant reduction in lung metastasis in those experiments. Conclusion: Taken together, this study demonstrates that co-delivery of everolimus and vinorelbine with a tumor-targeted liposomal formulation is an effective approach to achieve improved therapeutic outcome in RCC.

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“…With the maturation of biotechnology and peptide synthesis technology, more and more peptide drugs have been developed and applied in clinical practice. Due to the wide range of indications, high safety and significant efficacy, peptide drugs have been widely used in the prevention, diagnosis and treatment of diseases such as cancer, hepatitis and diabetes, which have broad prospects for development [ 11 , 28 ]. However, polypeptide drugs also have unavoidable limitations, including their easy degradation by proteases, short half-life and instability [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

The Protective Effect of a Long-Acting and Multi-Target HM-3-Fc Fusion Protein in Rheumatoid Arthritis

Huang

Wang

et al. 2018

IJMS

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Current treatment of rheumatoid arthritis (RA) is limited by relative shortage of treatment targets. HM-3 is a novel anti-RA polypeptide consisting of 18 amino acids with integrin αVβ3 and α5β1 as targets. Previous studies confirmed that HM-3 effectively inhibited the synovial angiogenesis and the inflammatory response. However, due to its short half-life, the anti-RA activity was achieved by frequent administration. To extend the half-life of HM-3, we designed a fusion protein with name HM-3-Fc, by combination of modified Fc segment of immunoglobulin 4 (IgG4) with HM-3 polypeptide. In vitro cell experiments demonstrated that HM-3-Fc inhibited the proliferation of splenic lymphocytes and reduced the release of TNF-α from macrophages. The pharmacodynamics studies on mice paw in Collagen-Induced Arthritis (CIA) model demonstrated that HM-3-Fc administered once in 5 days in the 50 and 25 mg/kg groups, or once in 7 days in the 25 mg/kg group showed a better protective effect within two weeks than the positive control adalimumab and HM-3 group. Preliminary pharmacokinetic studies in cynomolgus confirmed that the in vivo half-life of HM-3-Fc was 15.24 h in comparison with 1.32 min that of HM-3, which demonstrated that an Fc fusion can effectively increase the half-life of HM-3 and make it possible for further reduction of subcutaneous injection frequency. Fc-HM-3 is a long-acting active molecule for RA treatment.

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Advances in Tumor Targeted Liposomes

Cited by 60 publications

References 127 publications

Liposomal Nanostructures for Drug Delivery in Gastrointestinal Cancers

Liposomal Nanostructures for Drug Delivery in Gastrointestinal Cancers

<p>Co-delivery of everolimus and vinorelbine via a tumor-targeted liposomal formulation inhibits tumor growth and metastasis in RCC</p>

The Protective Effect of a Long-Acting and Multi-Target HM-3-Fc Fusion Protein in Rheumatoid Arthritis

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