04 Sep Scientists Develop Nanocarrier To Deliver Personalized Cocktail of Medications Directly to Tumor
MedicalResearch.com Interview with:
Adam G Alani, PhD
Associate Professor of Pharmaceutical Sciences
Department of Pharmaceutical Sciences
College of Pharmacy
Oregon State University-Oregon Health & Science University
Affiliate Assistant Professor
Department of Biomedical Engineering
School of Medicine at Oregon Health & Science University
Oregon State University-Portland Campus at OHSU
MedicalResearch.com: What is the background for this study?
Response: Current chemotherapeutic regimens while effective are difficult for patients and affect their quality of life. Our research tackles this issue by designing a nanotherapy that can deliver multiple chemotherapeutic agents by targeting the entire tumor microenvironment and not just the cancer cells and by reducing drug resistance. This, then is intended to simplify the treatment regimen, reduce drug related side effects and extends the life of the drugs by preventing resistance should the patient need it in the future. Thus, the ultimate underlying goal is to improve the patient’s quality of life by not just maximizing the drug’s efficacy but also trying to decrease its impact on the overall lifestyle of the individual.
MedicalResearch.com: What are the main findings?
Response: The findings of this work are:
1. Development of a new nanocarrier based on biocompatible/biodegradable poly-amino acid for the delivery of multiple anticancer drugs for the treatment of ovarian cancer.
2. The nanocarrier formulation when dosed to mice at frequent low doses mimicking a metronomic regimen inhibits ovarian cancer cell proliferation as well as angiogenesis. Thus, the nanocarrier formulation is capable of affecting the entire tumor microenvironment.
3. The developed nanocarrier can deliver the chemotherapeutic agents, paclitaxel and rapamycin, individually or in combination allowing for tailored dosing regimens.
4. The developed nanocarrier can deliver paclitaxel and rapamycin at safely at doses much higher than the commercially available formulations allowing for their potential use in traditional MTD based treatment regimens.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: The next step is to assess the effect of the developed nanocarriers on the immune response in ovarian cancer orthotopic model with a competent immune system. Many studies have shown that metronomic dosing of a chemotherapeutic agent such as paclitaxel and rapamycin can renormalize the immune response and thereby re-establish the natural ability of the body to fight the tumor itself.
In addition, we need to evaluate the pharmacokinetic profiles of the formulated nanocarriers in rodents and their efficacy and the safety in large animal models. These data are required by the FDA to file an Investigational New Drug Application, which the first step of bring the new technology to the market and achieve our ultimate goal of positively impacting patient’s quality of life.
MedicalResearch.com: Is there anything else you would like to add?
Response: Nanocarriers are efficient drug delivery systems that can be adapted for the simultaneous delivery of multiple drugs for the treatment of cancer and other diseases. These delivery systems can change the pharmacokinetic profile of existing drugs which can help produce new pharmacological effects that are not possible with the current commercial formulation. Our work is great example in which a conventional chemotherapeutic agent such as paclitaxel that in is used for direct effects on cancer cell proliferation is being repurposed and extended to target the entire tumor microenvironment through different mechanism of actions such as antiangiogenic and re-establishing the immune response. This type of approach allows clinicians to fully utilize the existing chemotherapeutics and tailor personalized dosing regimens for patients to achieve optimal outcomes.
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Deepa A. Rao, Gyan Mishra, Bhuvana Shyam Doddapaneni, Sergiy Kyryachenko, Igor H. Wierzbicki, Duc X. Ngyuen, Vidhi Shah, Adel M. Al Fatease, Raid G. Alany, Adam W. G. Alani. Combinatorial Polymeric Conjugated Micelles with Dual Cytotoxic and Antiangiogenic Effects for the Treatment of Ovarian Cancer. Chemistry of Materials, 2016; DOI: 10.1021/acs.chemmater.6b01280
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