Personalized Nanomedicine: A Revolution at the Nanoscale

Nanomedicine is an interdisciplinary research field that results from the application of nanotechnology to medicine and has the potential to significantly improve some current treatments. Specifically, in the field of personalized medicine, it is expected to have a great impact in the near future due to its multiple advantages, namely its versatility to adapt a drug to a cohort of patients. In the present review, the properties and requirements of pharmaceutical dosage forms at the nanoscale, so-called nanomedicines, are been highlighted. An overview of the main current nanomedicines in pre-clinical and clinical development is presented, detailing the challenges to the personalization of these therapies. Next, the process of development of novel nanomedicines is described, from their design in research labs to their arrival on the market, including considerations for the design of nanomedicines adapted to the requirements of the market to achieve safe, effective, and quality products. Finally, attention is given to the point of view of the pharmaceutical industry, including regulation issues applied to the specific case of personalized medicine. The authors expect this review to be a useful overview of the current state of the art of nanomedicine research and industrial production, and the future opportunities of personalized medicine in the upcoming years. The authors encourage the development and marketing of novel personalized nanomedicines.

[1]  Martin G Pomper,et al.  State-of-the-art in design rules for drug delivery platforms: lessons learned from FDA-approved nanomedicines. , 2014, Journal of controlled release : official journal of the Controlled Release Society.

[2]  Robert J. Gillies,et al.  A microenvironmental model of carcinogenesis , 2008, Nature Reviews Cancer.

[3]  R. Coleman,et al.  Equivalency challenge: Evaluation of Lipodox® as the generic equivalent for Doxil® in a human ovarian cancer orthotropic mouse model. , 2016, Gynecologic oncology.

[4]  S. Mitragotri,et al.  Nanoparticles in the clinic , 2016, Bioengineering & translational medicine.

[5]  S. Moghimi,et al.  Defining and characterizing non-biological complex drugs (NBCDs) – Is size enough? The case for liposomal doxorubicin generics (‘liposomal nanosimilars’) for injection , 2014 .

[6]  Yana K Reshetnyak,et al.  Advanced targeted nanomedicine. , 2015, Journal of biotechnology.

[7]  L. Boros,et al.  Acidosis induces reprogramming of cellular metabolism to mitigate oxidative stress , 2013, Cancer & metabolism.

[8]  Benjamin C. Tang,et al.  Managing diabetes with nanomedicine: challenges and opportunities , 2014, Nature Reviews Drug Discovery.

[9]  Young Jik Kwon,et al.  "Combo" nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy. , 2016, Advanced drug delivery reviews.

[10]  P. Soon-Shiong,et al.  SPARC Expression Correlates with Tumor Response to Albumin-Bound Paclitaxel in Head and Neck Cancer Patients. , 2009, Translational oncology.

[11]  V. Weissig,et al.  Nanopharmaceuticals (part 2): products in the pipeline , 2015, International journal of nanomedicine.

[12]  T. Golub,et al.  Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion , 2012, Nature.

[13]  A. Stegh Toward personalized cancer nanomedicine - past, present, and future. , 2013, Integrative biology : quantitative biosciences from nano to macro.

[14]  Mingying Yang,et al.  Phage-Enabled Nanomedicine: From Probes to Therapeutics in Precision Medicine. , 2017, Angewandte Chemie.

[15]  Tracy K. Pettinger,et al.  Nanopharmaceuticals (part 1): products on the market , 2014, International journal of nanomedicine.

[16]  N. Gu,et al.  The Smart Drug Delivery System and Its Clinical Potential , 2016, Theranostics.

[17]  Christine Vauthier,et al.  Polymer Nanoparticles for Nanomedicines , 2016, Springer International Publishing.

[18]  D. V. Bazile,et al.  Nanotechnologies in Drug Delivery - An Industrial Perspective , 2014 .

[19]  R. Alemany,et al.  A NOTCH-sensitive uPAR-regulated oncolytic adenovirus effectively suppresses pancreatic tumor growth and triggers synergistic anticancer effects with gemcitabine and nab-paclitaxel , 2017, Oncotarget.

[20]  Glen J Weiss,et al.  Phase I Study of PSMA-Targeted Docetaxel-Containing Nanoparticle BIND-014 in Patients with Advanced Solid Tumors , 2016, Clinical Cancer Research.

[21]  Has nanomedicine lived up to its promise? , 2014, Nanotechnology.

[22]  Deniz A. Bölükbas,et al.  Lung cancer nanomedicine: potentials and pitfalls. , 2015, Nanomedicine.

[23]  R. Hayeshi,et al.  State of the art and future directions in nanomedicine for tuberculosis , 2013, Expert opinion on drug delivery.

[24]  G. Ponchel,et al.  Polymer Nanoparticles for Nanomedicines. A Guide for their Design, Preparation and Development. , 2017, Anticancer research.

[25]  W J Stark,et al.  Industrial applications of nanoparticles. , 2015, Chemical Society reviews.

[26]  Ö. Türeci,et al.  Mutanome Engineered RNA Immunotherapy: Towards Patient-Centered Tumor Vaccination , 2015, Journal of immunology research.

[27]  I. Chourpa,et al.  Optimization of iron oxide nanoparticles encapsulation within poly(d,l-lactide-co-glycolide) sub-micron particles. , 2007, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[28]  J. B. Hall,et al.  Characterization of nanoparticles for therapeutics. , 2007, Nanomedicine.

[29]  Kristofer J. Thurecht,et al.  Nanoparticle-Based Medicines: A Review of FDA-Approved Materials and Clinical Trials to Date , 2016, Pharmaceutical Research.

[30]  Dong Soo Lee,et al.  Nanomedicine: Past, present and future - A global perspective. , 2015, Biochemical and biophysical research communications.

[31]  Morteza Mahmoudi,et al.  Protein-Nanoparticle Interactions , 2013 .

[32]  Amber Hoskins Genetic and Rare Diseases Information Center (CARD) , 2006, Medical reference services quarterly.

[33]  J. Benoit,et al.  Brain targeting using novel lipid nanovectors. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[34]  Thomas S. Woodson Public private partnerships and emerging technologies: A look at nanomedicine for diseases of poverty , 2016 .

[35]  Xiaoyang Xu,et al.  Cancer Nanomedicine: From Targeted Delivery to Combination Therapy , 2015, Trends in molecular medicine.

[36]  S. Svenson,et al.  What nanomedicine in the clinic right now really forms nanoparticles? , 2014, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[37]  A. Shelling,et al.  Nanoparticle therapeutics: Technologies and methods for overcoming cancer. , 2015, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[38]  Finbarr Murphy,et al.  Impact and effectiveness of risk mitigation strategies on the insurability of nanomaterial production: evidences from industrial case studies , 2015, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[39]  E. Shapiro,et al.  Magnetic poly(lactide‐co‐glycolide) and cellulose particles for MRI‐based cell tracking , 2011, Magnetic resonance in medicine.

[40]  Y. Pathak,et al.  Drug Delivery Nanoparticles Formulation and Characterization , 2009 .

[41]  Shannon Fischer,et al.  Regulating nanomedicine: new nano tools offer great promise for the future-if regulators can solve the difficulties that hold development back , 2014, IEEE Pulse.

[42]  S. Parveen,et al.  Nanomedicine: clinical applications of polyethylene glycol conjugated proteins and drugs. , 2006, Clinical pharmacokinetics.

[43]  Yang Sun,et al.  Superparamagnetic PLGA-iron oxide microcapsules for dual-modality US/MR imaging and high intensity focused US breast cancer ablation. , 2012, Biomaterials.

[44]  V. Venditto,et al.  Cancer nanomedicines: so many papers and so few drugs! , 2013, Advanced drug delivery reviews.

[45]  Regulating nanomedicine. , 2007, Nature materials.

[46]  Kenneth A Dawson,et al.  Nanoparticle adhesion to the cell membrane and its effect on nanoparticle uptake efficiency. , 2013, Journal of the American Chemical Society.

[47]  V. Torchilin,et al.  Drug targeting. , 2000, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[48]  T. Xia,et al.  Understanding biophysicochemical interactions at the nano-bio interface. , 2009, Nature materials.

[49]  H. Karanth,et al.  pH‐Sensitive liposomes‐principle and application in cancer therapy , 2007, The Journal of pharmacy and pharmacology.

[50]  Spiros Vamvakas,et al.  On the edge of new technologies (advanced therapies, nanomedicines). , 2011, Drug discovery today. Technologies.

[51]  J. Reynolds,et al.  Nanomedicine applied to translational oncology: A future perspective on cancer treatment. , 2016, Nanomedicine : nanotechnology, biology, and medicine.

[52]  L. John Burbidgh,et al.  Products to market , 1993 .

[53]  P. Couvreur,et al.  Nanomedicines and stroke: Toward translational research , 2015 .

[54]  Jörg Huwyler,et al.  Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications. , 2015, Journal of controlled release : official journal of the Controlled Release Society.

[55]  R. Duncan,et al.  Nanomedicine(s) under the microscope. , 2011, Molecular pharmaceutics.

[56]  V. Préat,et al.  PLGA-based nanoparticles: an overview of biomedical applications. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[57]  R. Duncan,et al.  Next-generation nanomedicines and nanosimilars: EU regulators' initiatives relating to the development and evaluation of nanomedicines. , 2013, Nanomedicine.

[58]  Wen Jiang,et al.  Designing nanomedicine for immuno-oncology , 2017, Nature Biomedical Engineering.

[59]  R. Gillies,et al.  Drug resistance and cellular adaptation to tumor acidic pH microenvironment. , 2011, Molecular pharmaceutics.

[60]  J. Kreuter,et al.  Drug delivery to the central nervous system by polymeric nanoparticles: what do we know? , 2014, Advanced drug delivery reviews.

[61]  Sarah Hurst Petrosko,et al.  Accelerating the Translation of Nanomaterials in Biomedicine. , 2015, ACS nano.

[62]  J. Lovrić,et al.  Nanotherapeutics in the EU: an overview on current state and future directions , 2014, International journal of nanomedicine.

[63]  Nanobiotech in big pharma: a business perspective. , 2017, Nanomedicine.

[64]  Cristina Fornaguera,et al.  Methods for the In Vitro Characterization of Nanomedicines—Biological Component Interaction , 2017, Journal of personalized medicine.

[65]  Luisa M Russell,et al.  State-ofthe-Art in Design Rules for Drug Delivery Platforms : Lessons from FDA-approved Nanomedicines , 2014 .

[66]  Peter D Brown,et al.  Nanomedicine: a pharma perspective. , 2015, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[67]  Michael D Kaminski,et al.  Synthesis and characterization of highly-magnetic biodegradable poly(d,l-lactide-co-glycolide) nanospheres. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[68]  Xue-Qing Zhang,et al.  Interactions of nanomaterials and biological systems: Implications to personalized nanomedicine. , 2012, Advanced drug delivery reviews.

[69]  Jennifer I. Hare,et al.  Challenges and strategies in anti-cancer nanomedicine development: An industry perspective. , 2017, Advanced drug delivery reviews.

[70]  Catarina Pinto Reis,et al.  Nanoencapsulation I. Methods for preparation of drug-loaded polymeric nanoparticles. , 2006, Nanomedicine : nanotechnology, biology, and medicine.

[71]  R. Bosetti Cost-effectiveness of nanomedicine: the path to a future successful and dominant market? , 2015, Nanomedicine.

[72]  Brenda Baggett,et al.  Tumor acidity, ion trapping and chemotherapeutics. I. Acid pH affects the distribution of chemotherapeutic agents in vitro. , 2003, Biochemical pharmacology.

[73]  Arthur G Erdman,et al.  The big picture on nanomedicine: the state of investigational and approved nanomedicine products. , 2013, Nanomedicine : nanotechnology, biology, and medicine.

[74]  Man Liu,et al.  Nanomedicine Drug Development: A Scientific Symposium Entitled “Charting a Roadmap to Commercialization” , 2014, The AAPS Journal.

[75]  N. Durán,et al.  Nanopharmaceuticals as a solution to neglected diseases: Is it possible? , 2017, Acta tropica.

[76]  Brian Godman,et al.  Risk sharing arrangements for pharmaceuticals: potential considerations and recommendations for European payers , 2010, BMC health services research.

[77]  B. Ruozi,et al.  Nanomedicine and neurodegenerative disorders: so close yet so far , 2015, Expert opinion on drug delivery.