Translational considerations for cancer nanomedicine.

There are many important considerations during preclinical development of cancer nanomedicines, including: 1) unique aspects of animal study design; 2) the difficulties in evaluating biological potency, especially for complex formulations; 3) the importance of analytical methods that can determine platform stability in vivo, and differentiate bound and free active pharmaceutical ingredient (API) in biological matrices; and 4) the appropriateness of current dose scaling techniques for estimation of clinical first-in-man dose from preclinical data. Biologics share many commonalities with nanotechnology products with regard to complexity and biological attributes, and can, in some cases, provide context for dealing with these preclinical issues. In other instances, such as the case of in vivo stability analysis, new approaches are required. This paper will discuss the significance of these preclinical issues, and present examples of current methods and best practices for addressing them. Where possible, these recommendations are justified using the existing regulatory guidance literature.

[1]  G. Borchardt,et al.  Body distribution of 75Se-radiolabeled silica nanoparticles covalently coated with omega-functionalized surfactants after intravenous injection in rats. , 1994, Journal of drug targeting.

[2]  Kazunori Kataoka,et al.  Preparation and biological characterization of polymeric micelle drug carriers with intracellular pH-triggered drug release property: tumor permeability, controlled subcellular drug distribution, and enhanced in vivo antitumor efficacy. , 2005, Bioconjugate chemistry.

[3]  T. Niidome,et al.  The effects of PEG grafting level and injection dose on gold nanorod biodistribution in the tumor-bearing mice. , 2009, Journal of controlled release : official journal of the Controlled Release Society.

[4]  Chung-Min Liao,et al.  Model-based assessment for human inhalation exposure risk to airborne nano/fine titanium dioxide particles. , 2008, The Science of the total environment.

[5]  G. Winkler.  Pulmonary intravascular macrophages in domestic animal species: review of structural and functional properties. , 1988, The American journal of anatomy.

[6]  Thierry Lavé,et al.  Physiologically based pharmacokinetic (PBPK) modeling of disposition of epiroprim in humans. , 2003, Journal of pharmaceutical sciences.

[7]  R K Jain,et al.  Biodistribution of monoclonal antibodies: scale-up from mouse to human using a physiologically based pharmacokinetic model. , 1995, Cancer research.

[8]  I. Mahmood.  Pharmacokinetic allometric scaling of antibodies: application to the first-in-human dose estimation. , 2009, Journal of pharmaceutical sciences.

[9]  M. Relling,et al.  Clinical Pharmacokinetics of Paclitaxel , 1994, Clinical pharmacokinetics.

[10]  Thierry Lavé,et al.  Application of full physiological models for pharmaceutical drug candidate selection and extrapolation of pharmacokinetics to man. , 2005, Basic & clinical pharmacology & toxicology.

[11]  J. Trethewey.  Bio-assays for the analysis of insulin. , 1989, Journal of pharmaceutical and biomedical analysis.

[12]  J. Brain,et al.  Pulmonary intravascular macrophages: their contribution to the mononuclear phagocyte system in 13 species. , 1999, American journal of physiology. Lung cellular and molecular physiology.

[13]  Scott E McNeil,et al.  Nanotechnology for the biologist , 2005, Journal of leukocyte biology.

[14]  P. Couvreur,et al.  Acute Renal Toxicity of Doxorubicin (Adriamycin)-Loaded Cyanoacrylate Nanoparticles , 2004, Pharmaceutical Research.

[15]  S. Batra,et al.  A physiologically based pharmacokinetic (PBPK) model to characterize and predict the disposition of monoclonal antibody CC49 and its single chain Fv constructs. , 2008, International immunopharmacology.

[16]  Saber M Hussain,et al.  Modeling the In Vivo Case with In Vitro Nanotoxicity Data , 2008, International journal of toxicology.

[17]  Mansoor M. Amiji,et al.  Nanotechnology for Cancer Therapy , 2006 .

[18]  Thommey P. Thomas,et al.  Preclinical antitumor efficacy evaluation of dendrimer-based methotrexate conjugates , 2008, Anti-cancer drugs.

[19]  C C Travis,et al.  Interspecific scaling of toxicity data. , 1988, Risk analysis : an official publication of the Society for Risk Analysis.

[20]  M. Christian,et al.  Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials , 2001, British Journal of Cancer.

[21]  R. Ramanujan,et al.  Thermoresponsive magnetic composite nanomaterials for multimodal cancer therapy. , 2010, Acta biomaterialia.

[22]  L. Huang,et al.  Role of liposome size and RES blockade in controlling biodistribution and tumor uptake of GM1-containing liposomes. , 1992, Biochimica et biophysica acta.

[23]  Theresa M. Allen,et al.  Antitumor activity of an epithelial cell adhesion molecule–targeted nanovesicular drug delivery system , 2007, Molecular Cancer Therapeutics.

[24]  Parag Aggarwal,et al.  Preclinical studies to understand nanoparticle interaction with the immune system and its potential effects on nanoparticle biodistribution. , 2008, Molecular pharmaceutics.

[25]  K. Kairemo,et al.  Development of a PBPK model for monoclonal antibodies and simulation of human and mice PBPK of a radiolabelled monoclonal antibody. , 2009, Current pharmaceutical design.

[26]  F Y Bois,et al.  Interspecies extrapolation: a reexamination of acute toxicity data. , 1992, Risk analysis : an official publication of the Society for Risk Analysis.

[27]  Huibi Xu,et al.  A novel method for the separation and determination of non-encapsulated pyrene in plasma and its application in pharmacokinetic studies of pyrene-loaded MPEG–PLA based nanoparticles , 2009, Nanotechnology.

[28]  W. Figg,et al.  Quantitative determination of total and unbound paclitaxel in human plasma following Abraxane treatment. , 2008, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[29]  H. Gremlich,et al.  Fluorescent nanoprobes as a biomarker for increased vascular permeability: implications in diagnosis and treatment of cancer and inflammation. , 2010, Bioconjugate chemistry.

[30]  Eiki Igarashi.  Factors affecting toxicity and efficacy of polymeric nanomedicines. , 2008, Toxicology and applied pharmacology.

[31]  Mina Choi,et al.  The impact of size on tissue distribution and elimination by single intravenous injection of silica nanoparticles. , 2009, Toxicology letters.

[32]  Nakissa Sadrieh,et al.  Regulatory perspective on the importance of ADME assessment of nanoscale material containing drugs. , 2009, Advanced drug delivery reviews.

[33]  A. Levin.  A review of the issues in the pharmacokinetics and toxicology of phosphorothioate antisense oligonucleotides. , 1999, Biochimica et biophysica acta.

[34]  H. Harashima,et al.  Optimization of antitumor effect of liposomally encapsulated doxorubicin based on simulations by pharmacokinetic/pharmacodynamic modeling. , 1999, Journal of controlled release : official journal of the Controlled Release Society.

[35]  Chang-Ho Ahn,et al.  Regulatory considerations for preclinical development of anticancer drugs , 1997, Cancer Chemotherapy and Pharmacology.

[36]  C. Liao,et al.  Assessing the airborne titanium dioxide nanoparticle-related exposure hazard at workplace. , 2009, Journal of hazardous materials.

[37]  Ruchika Nijhara,et al.  Bringing nanomedicines to market: regulatory challenges, opportunities, and uncertainties. , 2006, Nanomedicine : nanotechnology, biology, and medicine.

[38]  I. Mahmood.  Interspecies scaling of protein drugs: prediction of clearance from animals to humans. , 2004, Journal of pharmaceutical sciences.

[39]  Petra Krystek,et al.  Particle size-dependent organ distribution of gold nanoparticles after intravenous administration. , 2008, Biomaterials.

[40]  Jing Yong Ye,et al.  Investigation of tumor cell targeting of a dendrimer nanoparticle using a double-clad optical fiber probe. , 2008, Journal of biomedical optics.

[41]  Theresa M Allen,et al.  Rate of biodistribution of STEALTH liposomes to tumor and skin: influence of liposome diameter and implications for toxicity and therapeutic activity. , 2003, Biochimica et biophysica acta.

[42]  M. Dobrovolskaia,et al.  Preclinical Characterization of Engineered Nanoparticles Intended for Cancer Therapeutics , 2006 .

[43]  S. Strychor,et al.  Plasma, Tumor, and Tissue Disposition of STEALTH Liposomal CKD-602 (S-CKD602) and Nonliposomal CKD-602 in Mice Bearing A375 Human Melanoma Xenografts , 2007, Clinical Cancer Research.

[44]  G. Oberdörster,et al.  Safety assessment for nanotechnology and nanomedicine: concepts of nanotoxicology , 2010, Journal of internal medicine.

[45]  O. Kretz,et al.  IN VITRO BLOOD DISTRIBUTION AND PLASMA PROTEIN BINDING OF THE IRON CHELATOR DEFERASIROX (ICL670) AND ITS IRON COMPLEX FE-[ICL670]2 FOR RAT, MARMOSET, RABBIT, MOUSE, DOG, AND HUMAN , 2006, Drug Metabolism and Disposition.

[46]  Scott E McNeil,et al.  Rapid Distribution of Liposomal Short-Chain Ceramide in Vitro and in Vivo , 2008, Drug Metabolism and Disposition.

[47]  E J Freireich,et al.  Quantitative comparison of toxicity of anticancer agents in mouse, rat, hamster, dog, monkey, and man. , 1966, Cancer chemotherapy reports.

[48]  Anika Ashok,et al.  Guidance for Industry by U.S. Department of Health and Human Services—Food and Drug Administration—Center for Biologics Evaluation and Research (CBER)—February 1999 , 2009 .