Barriers to advancing nanotechnology to better improve and translate nanomedicines

Abstract

Engineered nanomaterials and nanotechnologies promise many benefits to enhance both in vitro and in vivo performance. This is now manifest in the increasing number of reported biomedical products under development and testing that contain nanotechnologies as their distinguishing performance—enhancing components. In many cases, nano-sized materials are selected to provide a specific functional aspect that contributes to improved medical performance, either in vitro or in vivo. Nanoparticles are most commonly exploited in diverse roles in topical lotions and creams, solubilization aids, for in vitro and in vivo diagnostic and targeting agents in nanomedicines and theranostics. Despite fundamental scientific excitement and many claims to nanotechnology-based improvements in new biomedical applications, several fundamental and long-standing challenges remain to be addressed using nanomedicines to make clinically important progress. This review addresses several issues that must be fairly and objectively reported and then overcome to provide truly credible performance for nanomedicines.

Keywords

nanotechnology / nanomedicine / drug delivery / therapeutic / target delivery

References

[1] Etheridge M L, Campbell S A, Erdman A G, Haynes C L, Wolf S M, McCullough J. The big picture on nanomedicine: The state of investigational and approved nanomedicine products. Nanomedicine, 2013, 9: 1–14

[2] Bawa R. Nanoparticle-based therapeutics in humans: A survey. Nanotechnology Law & Business, 2008, 5: 135–155

[3] Ventola C L. The nanomedicine revolution. Part 2: Current and future clinical applications. Pharmacy and Therapeutics, 2012, 37(10): 582–591

[4] Bawa R. Regulating nanomedicine—Can the FDA handle it? Current Drug Delivery, 2011, 8: 227–234

[5] Vashist S K, Venkatesh A G, Mitsakakis K, Czilwik G, Roth G, Stetten F, Zengerle R. Nanotechnology-based biosensors and diagnostics: Technology push versus industrial/healthcare requirements. BioNanoScience, 2012, 2: 115–126

[6] Robert J, Fisher T P. Form nanoparticles via controlled crystallization. Chemical Engineering Progress, 2008, 33–39

[7] Tlmpe C. Drug solubilization strategies applying nanoparticulate formulation and solid dispersion approaches in drug development. Pharmacological Reviews, 2010, 13: 12–21

[8] Muller R H, Jacobs C, Kayser O. Nanosuspensions as particulate drug formulations in therapy. Rationale for development and what we can expect for the future. Advanced Drug Delivery Reviews, 2001, 47: 3–19

[9] Merisko-Liversidge E M, Liversidge G G. Drug nanoparticles: Formulating poorly water-soluble compounds. Toxicologic Patholo-gy, 2008, 36: 43–48

[10] Johnson K C. Comparison of methods for predicting dissolution and the theoretical implications of particle-size-dependent solubility. Journal of Pharmaceutical Sciences, 2012, 101: 681–689

[11] Kaptay G. On the size and shape dependence of the solubility of nano-particles in solutions. International Journal of Pharmaceutics, 2012, 430: 253–257

[12] Merisko-Liversidge E, Liversidge G G. Nanosizing for oral and parenteral drug delivery: A perspective on formulating poorly-water soluble compounds using wet media milling technology. Advanced Drug Delivery Reviews, 2011, 63: 427–440

[13] Miele E, Spinelli G P, Miele E, Tomao F, Tomao S. Albumin-bound formulation of paclitaxel (Abraxane ABI-007) in the treatment of breast cancer. International Journal of Nanomedicine, 2009, 4: 99–105

[14] Raj S, Jose S, Sumod U S, Sabitha M. Nanotechnology in cosmetics: Opportunities and challenges. Journal of Pharmacy and Bioallied Sciences, 2012, 4: 186–193

[15] Wiechers J W, Musee N. Engineered inorganic nanoparticles and cosmetics: Facts, issues, knowledge gaps and challenges. Journal of Biomedical Nanotechnology, 2010, 6: 408–431

[16] Mu L, Sprando R L. Application of nanotechnology in cosmetics. Pharm Res, 2010, 27: 1746–1749

[17] Nohynek G J, Antignac E, Re T, Toutain H. Safety assessment of personal care products/cosmetics and their ingredients. Toxicology and Applied Pharmacology, 2010, 243: 239–259

[18] Ryman-Rasmussen J P, Riviere J E, Monteiro-Riviere N A. Penetration of intact skin by quantum dots with diverse physicochemical properties. Toxicological Sciences, 2006, 91: 159–165

[19] Rouse J G, Yang J, Ryman-Rasmussen J P, Barron A R, Monteiro-Riviere N A. Effects of mechanical flexion on the penetration of fullerene amino acid-derivatized peptide nanoparticles through skin. Nano Letters, 2007, 7: 155–160

[20] Corot C, Warlin D. Superparamagnetic iron oxide nanoparticles for MRI: Contrast media pharmaceutical company R&D perspective. Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology, 2013, 5(5): 411–422

[21] Lodhia J, Mandarano G, Ferris N, Eu P, Cowell S. Development and use of iron oxide nanoparticles (Part 1): Synthesis of iron oxide nanoparticles for MRI. Biomedical Imaging and Intervention Journal, 2010, 6: e12

[22] Huang C H, Tsourkas A. Gd-based macromolecules and nanoparticles as magnetic resonance contrast agents for molecular imaging. Current Topics in Medicinal Chemistry, 2013, 13: 411–421

[23] Schellenberger E A, Bogdanov A Jr, Hogemann D, Tait J, Weissleder R, Josephson L. Annexin V-CLIO: A nanoparticle for detecting apoptosis by MRI. Molecular Imaging, 2002, 1: 102–107

[24] Harisinghani M G, Barentsz J, Hahn P F, Deserno W M, Tabatabaei S, van de Kaa C H, de la Rosette J, Weissleder R. Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. The New England Journal of Medicine, 2003, 348: 2491–2499

[25] Fortina P, Kricka L J. Nanotechnology: Improving clinical testing? Clinical Chemistry, 2010, 56: 1384–1389

[26] Dobson M G, Galvin P, Barton D E. Emerging technologies for point-of-care genetic testing. Expert Review of Molecular Diagnostics, 2007, 7: 359–370

[27] Agasti S S, Rana S, Park M H, Kim C K, You C C, Rotello V M. Nanoparticles for detection and diagnosis. Advanced Drug Delivery Reviews, 2010, 62: 316–328

[28] Sanvicens N, Marco M P. Multifunctional nanoparticles—properties and prospects for their use in human medicine. Trends in Biotechnology, 2008, 26: 425–433

[29] Dandy D S, Wu P, Grainger D W. Array feature size influences nucleic acid surface capture in DNA microarrays. Proceedings of National Academy of Sciences of the United States of America, 2007, 104: 8223–8228

[30] Rao A N, Grainger D W. Biophysical properties of nucleic acids at surfaces relevant to microarray performance. Biomaterials Science, 2014, 2: 436–471

[31] Park K. Facing the truth about nanotechnology in drug delivery. ACS Nano, 2013, 7: 7442–7447

[32] Loeve S, Vincent B B, Gazeau F. Nanomedicine metaphors: From war to care. Emergence of an oecological approach. Nano Today, 2013, 8(6): 560–565

[33] Grainger D W, Castner D G. Nanobiomaterials and nanoanalysis: how to improve the nanoscience for biotechnology. Advanced Materials, 2008, 20: 867–877

[34] Crist R M, Grossman J H, Patri A K, Stern S T, Dobrovolskaia M A, Adiseshaiah P P, Clogston J D, McNeil S E. Common pitfalls in nanotechnology: Lessons learned from NCI’s nanotechnology characterization laboratory. Integrative Biology, 2013, 5: 66–73

[35] Richman E K, Hutchison J E. The nanomaterial characterization bottleneck. ACS Nano, 2009, 3: 2441–2446

[36] Buzea C, Pacheco I I, Robbie K. Nanomaterials and nanoparticles: Sources and toxicity. Biointerphases, 2007, 2: MR17-71

[37] Baer D R, Engelhard M H, Johnson G E, Laskin J, Lai J, Mueller K, Munusamy P, Thevuthasan S, Wang H, Washton N, Elder A, Baisch B L, Karakoti A, Kuchibhatla S V N T, Moon D. Surface characterization of nanomaterials and nanoparticles: Important needs and challenging opportunities. Journal of Vaccum Science & Technology A, 2013, 31: 50820

[38] Stirland D L, Nichols J W, Miura S, Bae Y H. Mind the gap: A survey of how cancer drug carriers are susceptible to the gap between research and practice. Journal of Controlled Release, 2013, 172: 1045–1064

[39] Begley C G, Ellis L M. Drug development: Raise standards for preclinical cancer research. Nature, 2012, 483: 531–533

[40] Ensign L M, Cone R, Hanes J. Oral drug delivery with polymeric nanoparticles: The gastrointestinal mucus barriers. Advanced Drug Delivery Reviews, 2012, 64: 557–570

[41] Yamanaka Y J, Leong K W. Engineering strategies to enhance nanoparticle-mediated oral delivery. Journal of Biomaterials Science, Polymer Edition, 2008, 19: 1549–1570

[42] Yuan H, Chen C Y, Chai G H, Du Y Z, Hu F Q. Improved transport and absorption through gastrointestinal tract by PEGylated solid lipid nanoparticles. Molecular Pharmaceitocs, 2013, 10: 1865–1873

[43] Hussain N, Jaitley V, Florence A T. Recent advances in the understanding of uptake of microparticulates across the gastrointestinal lymphatics. Advanced Drug Delivery Reviews, 2001, 50: 107–142

[44] Schleh C, Semmler-Behnke M, Lipka J, Wenk A, Hirn S, Schäffler M, Schmid G, Simon U, Kreyling W G. Size and surface charge of gold nanoparticles determine absorption across intestinal barriers and accumulation in secondary target organs after oral administration. Nanotoxicology, 2012, 6(1): 36–46

[45] Moghimi S M, Hunter A C, Murray J C. Long-circulating and target-specific nanoparticles: Theory to practice. Pharmacological Reviews, 2001, 53: 283–318

[46] Moghimi S M, Hunter A C, Murray J C. Nanomedicine: Current status and future prospects. FASEB Journal, 2005, 19: 311–330

[47] Bae Y H, Park K. Targeted drug delivery to tumors: Myths, reality and possibility. Journal of Controlled Release, 2011, 153: 198–205

[48] Kwon I K, Lee S C, Han B, Park K. Analysis on the current status of targeted drug delivery to tumors. Journal of Controlled Release, 2012, 164: 108–114

[49] Bertrand N, Leroux J C. The journey of a drug-carrier in the body: An anatomo-physiological perspective. Journal of Controlled Release, 2012, 161: 152–163

[50] Harris J M, Chess R B. Effect of pegylation on pharmaceuticals. Nature Reviews Drug Discovery, 2003, 2: 214–221

[51] Chambers E, Mitragotri S. Long circulating nanoparticles via adhesion on red blood cells: Mechanism and extended circulation. Experimental Biology and Medicine, 2007, 232: 958–966

[52] Rodriguez P L, Harada T, Christian D A, Pantano D A, Tsai R K, Discher D E. Minimal “self” peptides that inhibit phagocytic clearance and enhance delivery of nanoparticles. Science, 2013, 339: 971–975

[53] Fang R H, Hu C M, Zhang L. Nanoparticles disguised as red blood cells to evade the immune system. Expert Opinion on Biological Therapy, 2012, 12: 385–389

[54] Florence A T. “Targeting” nanoparticles: The constraints of physical laws and physical barriers. Journal of Controlled Release, 2012, 164: 115–124

[55] Gronow J R. Mechanisms of particle movement in porous media. Clay Minerals, 1986, 21: 753–767

[56] Pirollo K F, Chang E H. Does a targeting ligand influence nanoparticle tumor localization or uptake? Trends in Biotechnology, 2008, 26: 552–558

[57] Kirpotin D B, Drummond D C, Shao Y, Shalaby M R, Hong K, Nielsen U B, Marks J D, Benz C C, Park J W. Antibody targeting of long-circulating lipidic nanoparticles does not increase tumor localization but does increase internalization in animal models. Cancer Research, 2006, 66: 6732–6740

[58] Chauhan V P, Jain R K. Strategies for advancing cancer nanomedicine. Nature Materials, 2013, 12: 958–962

[59] Verma S, Miles D, Gianni L, Krop I E, Welslau M, Baselga J, Pegram M, Oh D Y, Diéras V, Guardino E, Fang L, Lu M W, Olsen S, Blackwell K. Trastuzumab emtansine for HER2-positive advanced breast cancer. The New England Journal of Medicine, 2012, 367: 1783–1791

[60] Al-Jamal K T. Active drug targeting: Lessons learned and new things to consider. International Journal of Pharmaceutics, 2013, 454: 525–526

[61] Lammers T, Kiessling F, Hennink W E, Storm G. Drug targeting to tumors: Principles, pitfalls and (pre-) clinical progress. Journal of Controlled Release, 2012, 161: 175–187

[62] Underwood J C, Carr I. The ultrastructure and permeability characteristics of the blood vessels of a transplantable rat sarcoma. The Journal of Pathology, 1972, 107: 157–166

[63] Peterson H I, Appelgren K L. Experimental studies on the uptake and rentention of labelled proteins in a rat tumour. European Journal of Cancer, 1973, 9(8): 543–547

[64] Matsumura Y, Maeda H. A new concept for macromolecular therapeutics in cancer chemotherapy: Mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Research, 1986, 46: 6387–6392

[65] Taurin S, Nehoff H, Greish K. Anticancer nanomedicine and tumor vascular permeability: Where is the missing link? Journal of Controlled Release, 2012, 164: 265–275

[66] Nichols J W, Bae Y H. EPR: Evidence and fallacy. Journal of Controlled Release, 2014, 190: 451–464

[67] Aaron M, Suzanne K L, Russell B, Lee M E, Zwelling L. A survey on data reproducibility in cancer research provides insights into our limited ability to translate findings from the laboratory to the clinic. PLOS ONE, 2013, doi: 10.1371/journal.pone.0063221

[68] Prinz F, Schlange T, Asadullah K. Believe it or not: How much can we rely on published data on potential drug targets? Nature Reviews Drug Discovery, 2011, 10: 712

[69] American Type Culture Collection Standards Development Organization Workgroup ASN-0002. Cell line misidentification: the beginning of the end. Nature Reviews Cancer, 2010, 10: 441–448

[70] Hughes P, Marshall D, Reid Y, Parkes H, Gelber C. The costs of using unauthenticated, over-passaged cell lines: How much more data do we need? Biotechniques, 2007, 43(5): 575, 577–578, 581–582 passim

[71] Hartung T. Look back in anger—what clinical studies tell us about preclinical work. Altex, 2013, 30(3): 275–291

[72] Peer D, Karp J M, Hong S, Farokhzad O C, Margalit R, Langer R. Nanocarriers as an emerging platform for cancer therapy. Nature Nanotechnology, 2007, 2: 751–760

[73] Crommelin D J, Florence A T. Towards more effective advanced drug delivery systems. International Journal of Pharmaceutics, 2013, 454: 496–511

[74] Venditto V J, Szoka F C Jr. Cancer nanomedicines: So many papers and so few drugs! Advanced Drug Delivery Reviews, 2013, 65: 80–88

[75] Paul S M, Mytelka D S, Dunwiddie C T, Persinger C C, Munos B H, Lindborg S R, Schacht A L. How to improve R&D productivity: The pharmaceutical industry’s grand challenge. Nature Reviews Drug Discovery, 2010, 9: 203–214

Acknowledgement

DWG is grateful to the George S. and Dolores DoréEccles Foundation (USA) for support.

RIGHTS & PERMISSIONS

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg