An orally delivered small-molecule formulation with antiangiogenic and anticancer activity
Ofra Benny,Ofer Fainaru,Avner Adini,Flavia Cassiola,Lauren Bazinet,Irit Adini,Elke Pravda,Yaakov Nahmias,Samir Koirala,Gabriel Corfas,Robert J. D'Amato,Judah Folkman +11 more
TLDR
Lodamin is an oral nontoxic antiangiogenic drug that can be chronically administered for cancer therapy or metastasis prevention and first reaches the liver, making it especially efficient in preventing the development of liver metastasis in mice.Abstract:
Targeting angiogenesis, the formation of blood vessels, is an important modality for cancer therapy. TNP-470, a fumagillin analog, is among the most potent and broad-spectrum angiogenesis inhibitors. However, a major clinical limitation is its poor oral availability and short half-life, necessitating frequent, continuous parenteral administration. We have addressed these issues and report an oral formulation of TNP-470, named Lodamin. TNP-470 was conjugated to monomethoxy-polyethylene glycol-polylactic acid to form nanopolymeric micelles. This conjugate can be absorbed by the intestine and selectively accumulates in tumors. Lodamin significantly inhibits tumor growth, without causing neurological impairment in tumor-bearing mice. Using the oral route of administration, it first reaches the liver, making it especially efficient in preventing the development of liver metastasis in mice. We show that Lodamin is an oral nontoxic antiangiogenic drug that can be chronically administered for cancer therapy or metastasis prevention.read more
Citations
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Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy.
TL;DR: This review offers a detailed description of different cytotoxic drug carriers, such as liposomes, carbon nanotubes, dendrimers, polymeric micelles,polymeric conjugates and polymeric nanoparticles, in passive and active targeted cancer therapy, by enhancing the permeability and retention or by the functionalization of the surface of the carriers.
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Polymer–drug conjugate therapeutics: advances, insights and prospects
TL;DR: The rational design, physicochemical characteristics and recent advances in the development of different classes of polymer–drug conjugates, including polymer–protein and polymer–small-molecule drug conjugating, dendrimers, polymer nanoparticles and multifunctional systems are discussed.
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Angiogenesis inhibitors: current strategies and future prospects.
Kristina M. Cook,William D. Figg +1 more
TL;DR: In this paper, a review describes key molecular mechanisms and novel therapies that are on the horizon for antiangiogenic tumor therapy, including growth factors, receptor tyrosine kinases, and transcription factors such as hypoxia inducible factor.
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Oral delivery of anticancer drugs: Challenges and opportunities
TL;DR: Various emerging trends to tackle the challenges associated with oral delivery of anticancer drugs are reviewed, which invariably include efflux transporter based-, functional excipient- and nanocarrier based-approaches.
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Polymeric micelles for oral drug delivery
Geneviève Gaucher,P.M Satturwar,Marie-Christine Jones,Alexandra Furtos,Jean-Christophe Leroux,Jean-Christophe Leroux +5 more
TL;DR: Other drug delivery strategies such as using bioadhesive polymers which may lengthen residence time in the GI tract and promote drug permeation, or rendering the polymeric micelles pH-sensitive in order to ensure drug release from the carrier at its site of absorption are reported.
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TL;DR: Synthesis of fumagillin analogues yielded potent angiogenesis inhibitors ('angioinhibins') which suppress the growth of a wide variety of tumours with relatively few side-effects.
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