Priming the body to receive the therapeutic agent to redefine treatment benefit/risk profile
| Autor: | Maxime Bergere, Agnès Pottier, Laurent Levy, Matthieu Germain, Marie-Edith Meyre, Francis Mpambani, Marion Paolini, Laurence Poul, Céline Berjaud |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Priming (immunology)
lcsh:Medicine Biological Availability Antineoplastic Agents Breast Neoplasms 02 engineering and technology Docetaxel Pharmacology Risk profile Article 03 medical and health sciences Mice 0302 clinical medicine Cytochrome P-450 Enzyme System Polylactic Acid-Polyglycolic Acid Copolymer medicine Tumor Cells Cultured Animals Cytochrome P-450 Enzyme Inhibitors Humans Tissue Distribution lcsh:Science Cell Proliferation Multidisciplinary business.industry lcsh:R 021001 nanoscience & nanotechnology Xenograft Model Antitumor Assays Acute toxicity Bioavailability Irinotecan Nanomedicine 030220 oncology & carcinogenesis Toxicity Liposomes lcsh:Q Female 0210 nano-technology business HT29 Cells medicine.drug |
| Zdroj: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-11 (2018) |
| ISSN: | 2045-2322 |
| Popis: | Many therapeutic agents offer a low useful dose (dose responsible for efficacy)/useless dose (dose eliminated or responsible for toxicity) ratio, mainly due to the fact that therapeutic agents must ensure in one single object all the functions required to deliver the treatment, which leads to compromises in their physico-chemical design. Here we introduce the concept of priming the body to receive the treatment by uncorrelating these functions into two distinct objects sequentially administered: a nanoprimer occupying transiently the main pathway responsible for therapeutic agent limited benefit/risk ratio followed by the therapeutic agent. The concept was evaluated for different nature of therapeutic agents: For nanomedicines we designed a liposomal nanoprimer presenting preferential hepatic accumulation without sign of acute toxicity. This nanoprimer was able to increase the blood bioavailability of nanomedicine correlated with a lower hepatic accumulation. Finally this nanoprimer markedly enhanced anti-tumor efficacy of irinotecan loaded liposomes in the HT-29 tumor model when compared to the nanomedicine alone. Then, for small molecules we demonstrated the ability of a cytochrome inhibitor loaded nanoprimer to increase efficacy of docetaxel treatment. These results shown that specific nanoprimers could be designed for each family of therapeutic agents to answer to their specific needs. |
| Databáze: | OpenAIRE |
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