Preclinical Efficacy and Toxicity Testing of Engineered Nanomaterials

Grossman, Jennifer; McNeil, Scott E.

doi:10.1159/000328889

Cited by 3 publications

(1 citation statement)

References 18 publications

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“…Much of current cancer research is focused on exploring novel targets and discovering new anticancer drugs. While the availability of new molecules certainly offers hope to patients who do not respond to existing drugs, development of each new molecule is associated with tremendous costs. , Many highly active drug candidates have been shelved because of poor physicochemical or pharmacokinetic characteristics. − Reformulation of such molecules can overcome their unfavorable biological behavior and would offer a less expensive approach to anticancer drug development. ,, …”

Section: Introductionmentioning

confidence: 99%

Reformulating Tylocrebrine in Epidermal Growth Factor Receptor Targeted Polymeric Nanoparticles Improves Its Therapeutic Index

et al. 2015

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Several promising anticancer drug candidates have been sidelined owing to their poor physicochemical properties or unfavorable pharmacokinetics, resulting in high overall cost of drug discovery and development. Use of alternative formulation strategies that alleviate these issues can help advance new molecules to the clinic at a significantly lower cost. Tylocrebrine is a natural product with potent anticancer activity. Its clinical trial was discontinued following the discovery of severe central nervous system toxicities. To improve the safety and potency of tylocrebrine, we formulated the drug in polymeric nanoparticles targeted to the epidermal growth factor receptor (EGFR) overexpressed on several types of tumors. Through in vitro studies in different cancer cell lines, we found that EGFR targeted nanoparticles were significantly more effective in killing tumor cells than the free drug. In vivo pharmacokinetic studies revealed that encapsulation in nanoparticles resulted in lower brain penetration and enhanced tumor accumulation of the drug. Further, targeted nanoparticles were characterized by significantly enhanced tumor growth inhibitory activity in a mouse xenograft model of epidermoid cancer. These results suggest that the therapeutic index of drugs that were previously considered unusable could be significantly improved by reformulation. Application of novel formulation strategies to previously abandoned drugs provides an opportunity to advance new molecules to the clinic at a lower cost. This can significantly increase the repertoire of treatment options available to cancer patients.

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Section: Introductionmentioning

confidence: 99%

Reformulating Tylocrebrine in Epidermal Growth Factor Receptor Targeted Polymeric Nanoparticles Improves Its Therapeutic Index

et al. 2015

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Nuclear Magnetic Resonance Spectroscopy in Nanomedicine

Lin

2014

Progress in Optical Science and Photonics

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Cytotoxicity of Poly(Alkyl Cyanoacrylate) Nanoparticles

Sulheim

Iversen

Nakstad

et al. 2017

IJMS

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Although nanotoxicology has become a large research field, assessment of cytotoxicity is often reduced to analysis of one cell line only. Cytotoxicity of nanoparticles is complex and should, preferentially, be evaluated in several cell lines with different methods and on multiple nanoparticle batches. Here we report the toxicity of poly(alkyl cyanoacrylate) nanoparticles in 12 different cell lines after synthesizing and analyzing 19 different nanoparticle batches and report that large variations were obtained when using different cell lines or various toxicity assays. Surprisingly, we found that nanoparticles with intermediate degradation rates were less toxic than particles that were degraded faster or more slowly in a cell-free system. The toxicity did not vary significantly with either the three different combinations of polyethylene glycol surfactants or with particle size (range 100–200 nm). No acute pro- or anti-inflammatory activity on cells in whole blood was observed.

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Preclinical Efficacy and Toxicity Testing of Engineered Nanomaterials

Cited by 3 publications

References 18 publications

Reformulating Tylocrebrine in Epidermal Growth Factor Receptor Targeted Polymeric Nanoparticles Improves Its Therapeutic Index

Reformulating Tylocrebrine in Epidermal Growth Factor Receptor Targeted Polymeric Nanoparticles Improves Its Therapeutic Index

Nuclear Magnetic Resonance Spectroscopy in Nanomedicine

Cytotoxicity of Poly(Alkyl Cyanoacrylate) Nanoparticles

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