Skip to main content

Advertisement

Log in

Nanomedicines: From Bench to Bedside and Beyond

  • Review Article
  • Theme: Nanotechnology in Complex Drug Products: Learning from the Past, Preparing for the Future
  • Published:
The AAPS Journal Aims and scope Submit manuscript

Abstract

Advancing nanomedicines from concept to clinic requires integration of new science with traditional pharmaceutical development. The medical and commercial success of nanomedicines is greatly facilitated when those charged with developing nanomedicines are cognizant of the unique opportunities and technical challenges that these products present. These individuals must also be knowledgeable about the processes of clinical and product development, including regulatory considerations, to maximize the odds for successful product registration. This article outlines these topics with a goal to accelerate the combination of academic innovation with collaborative industrial scientists who understand pharmaceutical development and regulatory approval requirements—only together can they realize the full potential of nanomedicines for patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Langer R, Weissleder R. Nanotechnol JAMA. 2015;313:135–6.

    CAS  Google Scholar 

  2. Finch G, Havel H, Analoui M, Barton RW, Diwan AR, Hennessy M, et al. Nanomedicine drug development: a scientific symposium entitled charting a roadmap to commercialization. AAPS J. 2014;16:1–7.

    Article  Google Scholar 

  3. Eaton MA, Levy L, Fontaine OM. Delivering nanomedicines to patients: a practical guide. Nanomed: Nanotechnol, Biol Med. 2015;11:983–92.

    CAS  Google Scholar 

  4. Prabhakar U, Maeda H, Jain RK, Sevick-Muraca EM, Zamboni W, Farokhzad OC, et al. Challenges and key considerations of the enhanced permeability and retention effect for nanomedicine drug delivery in oncology. Cancer Res. 2013;73:2412–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Harrington KJ, Mohammadtaghi S, Uster PS, Glass D, Peters AM, Vile RG, et al. Effective targeting of solid tumors in patients with locally advanced cancers by radiolabeled pegylated liposomes. Clin Cancer Res. 2001;7:243–54.

    CAS  PubMed  Google Scholar 

  6. Hendriks B, Shields A, Siegel BA, Miller K, Munster P, Ma C, et al. PET/CT imaging of 64Cu-labelled HER2 liposomal doxorubicin (64Cu-MM-302) quantifies variability of liposomal drug delivery to diverse tumor lesions in HER2-positive breast cancer patients. Ann Oncol. 2014;25:i19.

    Article  Google Scholar 

  7. Ramanathan RK, Korn RL, Sachdev JC, Fetterly GJ, Marceau K, Marsh V, et al. Abstract CT224: Pilot study in patients with advanced solid tumors to evaluate feasibility of ferumoxytol (FMX) as tumor imaging agent prior to MM-398, a nanoliposomal irinotecan (nal-IRI). Cancer Res. 2014;74:CT224.

    Article  Google Scholar 

  8. Low S, Von Hoff D, Mita M, Burris H, Eisenberg P, Hart L, et al. Prostate-specific membrane antigen (PSMA) expression as a potential patient selection marker in patients with refractory solid tumors administered BIND-014, a PSMA-targeted nanoparticle containing docetaxel. Cancer Res. 2014;74:911.

    Article  Google Scholar 

  9. Hrkach J, Von Hoff D, Ali MM, Andrianova E, Auer J, Campbell T, et al. Preclinical development and clinical translation of a PSMA-targeted docetaxel nanoparticle with a differentiated pharmacological profile. Sci Transl Med. 2012;4:128ra39.

    Article  PubMed  Google Scholar 

  10. Gabizon A, Shmeeda H, Barenholz Y. Pharmacokinetics of pegylated liposomal doxorubicin. Clin Pharmacokinet. 2003;42:419–36.

    Article  CAS  PubMed  Google Scholar 

  11. Sparreboom A, Scripture CD, Trieu V, Williams PJ, De T, Yang A, et al. Comparative preclinical and clinical pharmacokinetics of a cremophor-free, nanoparticle albumin-bound paclitaxel (ABI-007) and paclitaxel formulated in Cremophor (Taxol). Clin Cancer Res. 2005;11:4136–43.

    Article  CAS  PubMed  Google Scholar 

  12. Krishna R, Webb MS, Onge GS, Mayer LD. Liposomal and nonliposomal drug pharmacokinetics after administration of liposome-encapsulated vincristine and their contribution to drug tissue distribution properties. J Pharmacol Exp Ther. 2001;298:1206–12.

    CAS  PubMed  Google Scholar 

  13. Wei GL, Xiao SH, Gu Y, Si DY. Validated HPLC assay of liposome-encapsulated and non-liposomal doxorubicin in plasma and its application to pharmacokinetic study. J Pharm Pharmacol. 2010;10:229–36.

    Google Scholar 

  14. Ait-Oudhia S, Mager DE, Straubinger RM. Application of pharmacokinetic and pharmacodynamic analysis to the development of liposomal formulations for oncology. Pharmaceutics. 2014;6:137–74.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Drummond DC, Noble CO, Hayes ME, Park JW, Kirpotin DB. Pharmacokinetics and in vivo drug release rates in liposomal nanocarrier development. J Pharmaceutical Sci. 2008;97:4696–740.

    Article  CAS  Google Scholar 

  16. Johnson JI, Decker S, Zaharevitz D, Rubinstein LV, Venditti JM, Schepartz S, et al. Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials. Br J Cancer. 2001;84:1424.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Gould SE, Junttila MR, de Sauvage FJ. Translational value of mouse models in oncology drug development. Nat Med. 2015;21:431–9.

    Article  CAS  PubMed  Google Scholar 

  18. Caron WP, Morgan KP, Zamboni BA, Zamboni WC. A review of study designs and outcomes of phase I clinical studies of nanoparticle agents compared with small-molecule anticancer agents. Clin Cancer Res. 2013;19:3309–15.

    Article  CAS  PubMed  Google Scholar 

  19. Qiu S, Liu Z, Hou L, Li Y, Wang J, Wang H, et al. Complement activation associated with polysorbate 80 in beagle dogs. Int Immunopharmacol. 2013;15:144–9.

    Article  CAS  PubMed  Google Scholar 

  20. Masini E, Planchenault J, Pezziardi F, Gautier P, Gagnol JP. Histamine-releasing properties of polysorbate 80 in vitro and in vivo: correlation with its hypotensive action in the dog. Agents Actions. 1985;16:470–7.

    Article  CAS  PubMed  Google Scholar 

  21. Dobrovolskaia MA, McNeil SE. Understanding the correlation between in vitro and in vivo immunotoxicity tests for nanomedicines. J Control Release. 2013;172:456–66.

    Article  CAS  PubMed  Google Scholar 

  22. Casinghino S, Gauthier L, McClintock D, Boldenow E, Nauman C, Freeman GB, et al. In vitro methods to predict immune-mediated toxicities of dextran-based nanomaterial precursors in rats. Toxicologist. 2009;108:178.

    Google Scholar 

  23. Cruz CN, Tyner KM, Velazquez L, Hyams KC, Jacobs A, Shaw AB, et al. CDER risk assessment exercise to evaluate potential risks from the use of nanomaterials in drug products. AAPS J. 2013;15:1–6.

    Article  Google Scholar 

  24. Ashton S, Song YH, Nolan J, Cadogan E, Murray J, Odedra R, et al. Aurora kinase inhibitor nanoparticles target tumors with favorable therapeutic index in vivo. Sci Transl Med. 2016;8:325ra17.

    Article  PubMed  Google Scholar 

  25. Svenson S, Wolfgang M, Hwang J, Ryan J, Eliasof S. Preclinical to clinical development of the novel camptothecin nanopharmaceutical CRLX101. J Control Release. 2011;153:49–55.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Henry Havel.

Additional information

Guest Editors: Katherine Tyner, Sau (Larry) Lee, and Marc Wolfgang

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Havel, H., Finch, G., Strode, P. et al. Nanomedicines: From Bench to Bedside and Beyond. AAPS J 18, 1373–1378 (2016). https://doi.org/10.1208/s12248-016-9961-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12248-016-9961-7

Key words

Navigation