Nano Today
Volume 5, Issue 2, April 2010, Pages 143-159
Journal home page for Nano Today

Review
Targeted nanodelivery of drugs and diagnostics

https://doi.org/10.1016/j.nantod.2010.03.003Get rights and content

Summary

Nanomaterials for targeted delivery are uniquely capable of localizing delivery of therapeutics and diagnostics to diseased tissues. The ability to achieve high, local concentrations of drugs or image contrast agents at a target site provides the opportunity for improved system performance and patient outcomes along with reduced systemic dosing. In this review, the design of targeted nanodelivery systems is discussed with an emphasis on in vivo performance, the physicochemical properties that affect localization at the target site, and the incorporation of therapeutic drugs into these systems.

Introduction

Successful targeted delivery systems are designed to allow delivery of therapeutic or diagnostic agents to a preferential site. As targeted nanodelivery involves local delivery of therapeutics and diagnostics at disease sites, this method has received considerable attention over the last 15 years and is poised to have a significant impact on medicine. Efficient targeted delivery systems allow for a reduced systemic dosage while resulting in relatively higher or more efficient dosing at the target site. The promising benefits of reduced systemic side effects and simultaneously improved efficacy have fueled the development of this field. To date, targeted delivery has become a rich field of drug delivery and nanomaterials.

Nanoscale materials are a necessity for most targeted delivery systems as these systems must be allowed to transport through different tissue spaces in order to localize at the target site. For tumor delivery, intravenously administered particles must circulate in the bloodstream and be small enough to escape circulation through tumor microvasculature which typically requires the system to have a diameter less than 100 nm to 2 μm [1]. In other applications such as the treatment and diagnosis of atherosclerotic plaques, targeted delivery systems have been developed on the order of 10 nm to greater than 1 μm.

The ability of nanoparticles to localize at a target site is dependent on a number of factors. In general, it is unclear whether chemical properties, the presence of a targeting ligand, or size is the primary determinant for nanoparticle biodistribution. In many cases, it is a combination of these properties that shapes biodistribution. One of the advantages of nanoparticle delivery systems is that the circulation time of drugs and diagnostic agents can be prolonged, and delivery can be controlled through targeting.

Even with targeted delivery, only a fraction of the administered dose localizes at the target site while the remaining nanoparticles distribute throughout the body. At this point, pharmacokinetics pertaining to the nanodelivery system determine the dose in nontargeted tissues. A furthered understanding of nanoparticle biodistribution and pharmacokinetics will be a significant contribution to the successful development and translation of targeted delivery systems.

An often overlooked design parameter in targeted delivery systems is the method and amount of incorporation of the drug or diagnostic agent. There are a variety of methods for incorporating these functions into a delivery system which depend on the nanomaterial and the agent of interest. The small volumes of nanomaterials inherently limit their maximum payloads, and their sizes present challenges to traditional purification and measurement techniques.

From current work in the field, it is evident that the design of optimized targeted delivery systems will be based on the drug or agent of interest, the nanoparticle type that allows sufficient loading of the drug, and the physicochemical properties that allow for targeting. We will highlight some of this recent work on targeted delivery systems and focus on in vivo performance, localization, and the incorporation of diagnostic and therapeutic agents in targeted delivery systems.

Section snippets

In vivo studies on targeted delivery: localization, uptake, and performance

One of the key features of targeted delivery systems is the addition of targeting ligands to the surface of the nanoparticle either through physical adsorption or more commonly chemical attachment. Various in vitro and in vivo studies have shown that the addition of these targeting ligands improves the therapeutic effects of the delivery systems compared to control systems without the targeting ligands. Nanodelivery systems with targeting ligands are often referred to as actively targeted

The “fate” of the nanoparticle delivery system

The systemic biodistribution of nanoparticle delivery systems after administration is one of the most important issues and design elements to consider in targeted delivery. There is an innate relationship between the physicochemical properties of the nanoparticle and what happens to the particle after administration. This section will focus on the biodistribution, opsonization, and clearance of nanoparticles related to targeted delivery.

Incorporation and release of therapeutics from nanodelivery systems

The importance of controlling nanoparticle localization for targeted delivery is inconsequential if a particle cannot carry a relevant amount of drug and release it at the target site. The ability to efficiently incorporate a drug into nanoparticle delivery systems is dependent on the drug itself, the design of the nanoparticle, and the method of loading. Countless strategies have been used to synthesize organic nanoparticles with an intended application in drug delivery, however, only a

Conclusion

As the field of targeted drug delivery continues to move forward, it will be increasingly important to design nanoscale systems with tailorable properties for efficient delivery and improved therapeutic efficacy. Important design considerations will include the physicochemical properties that govern targeting, biodistribution, and clearance as well as the system's effectiveness in carrying, protecting, and even releasing active therapeutic and diagnostic agents.

The selection and addition of

Acknowledgments

This work was supported in part by the National Institutes of Health (grant EB000246 and a Physical Science-Oncology Centers U54 grant) and the National Science Foundation (grant DGE-03-33080).

Margaret A. Phillips received her Honors B.S. in biomedical engineering and Mathematics from Saint Louis University in 2006. She is currently a PhD student with Nicholas Peppas in biomedical engineering at the University of Texas at Austin where she is a Thrust 2000 fellow and an NSF-IGERT trainee. Her thesis focuses on the surface modification of anionic complexation hydrogels with polysaccharides for drug delivery applications. She is currently finishing a 3-year term as the National Student

References (80)

  • J.D. Byrne et al.

    Adv. Drug Deliv. Rev.

    (2008)
  • M.O. Oyewumi et al.

    J. Control. Release

    (2004)
  • A.K. Iyer et al.

    Drug Discov. Today

    (2006)
  • K.F. Pirollo et al.

    Trends Biotechnol.

    (2008)
  • D.E. Owens et al.

    Int. J. Pharm.

    (2006)
  • S.M. Moghimi et al.

    Prog. Lipid Res.

    (2003)
  • Y. Akiyama et al.

    J. Control. Release

    (2009)
  • G. Zhang et al.

    Biomaterials

    (2009)
  • W.H. De Jong et al.

    Biomaterials

    (2008)
  • L.C. Glangchai et al.

    J. Control. Release

    (2008)
  • K. Avgoustakis et al.

    Int. J. Pharm.

    (2003)
  • S.E. Dunn et al.

    J. Control. Release

    (1997)
  • T. Govender et al.

    J. Control. Release

    (1999)
  • L. Mu et al.

    J. Control. Release

    (2003)
  • C. Fonseca et al.

    J. Control. Release

    (2002)
  • Y.P. Li et al.

    J. Control. Release

    (2001)
  • K. Avgoustakis et al.

    J. Control. Release

    (2002)
  • R. Langer

    J. Control. Release

    (1991)
  • M. Agüeros et al.

    Eur. J. Pharm. Sci.

    (2009)
  • S.A. Agnihotri et al.

    J. Control. Release

    (2004)
  • J. Berger et al.

    Eur. J. Pharm. Biopharm.

    (2004)
  • Q. Gan et al.

    Colloid Surf. B

    (2007)
  • S. Mitra et al.

    J. Control. Release

    (2001)
  • A. Zahoor et al.

    Int. J. Antimicrob. Ag.

    (2005)
  • Y. Malam et al.

    Trends Pharmacol. Sci.

    (2009)
  • D.E. Discher et al.

    Prog. Polym. Sci.

    (2007)
  • A.V. Kabanov et al.

    J. Control. Release

    (2002)
  • K. Kataoka et al.

    Adv. Drug Deliv. Rev.

    (2001)
  • A.L. Lee et al.

    Biomaterials

    (2009)
  • R. Rastogi et al.

    Colloid Surf. B

    (2009)
  • J.M. Chan et al.

    Biomaterials

    (2009)
  • S. Ganta et al.

    J. Control. Release

    (2008)
  • Y. Qiu et al.

    Adv. Drug Deliv. Rev.

    (2001)
  • N.A. Peppas et al.

    Eur. J. Pharm. Biopharm.

    (2000)
  • T. Yamagata et al.

    J. Control. Release

    (2006)
  • M. Morishita et al.

    J. Control. Release

    (2006)
  • D. Guowei et al.

    Int. J. Pharm.

    (2007)
  • D. Missirlis et al.

    Eur. J. Pharm. Sci.

    (2006)
  • D.V. Bazile et al.

    Biomaterials

    (1992)
  • X. Wang et al.

    ACS Nano

    (2009)
  • Cited by (273)

    • Nanoconjugate formulations for enhanced drug delivery

      2023, Advanced and Modern approaches for Drug Delivery
    • Nanodiagnostics and targeted drug delivery: integrated technologies

      2023, Nanotechnology Principles in Drug Targeting and Diagnosis
    View all citing articles on Scopus

    Margaret A. Phillips received her Honors B.S. in biomedical engineering and Mathematics from Saint Louis University in 2006. She is currently a PhD student with Nicholas Peppas in biomedical engineering at the University of Texas at Austin where she is a Thrust 2000 fellow and an NSF-IGERT trainee. Her thesis focuses on the surface modification of anionic complexation hydrogels with polysaccharides for drug delivery applications. She is currently finishing a 3-year term as the National Student Chapter President of the Society For Biomaterials.

    Martin L. Gran received his B.S. in chemical engineering from Iowa State University in 2006. He is currently pursuing a PhD at the University of Texas at Austin in chemical engineering under the guidance of Dr. Nicholas A. Peppas. At the University of Texas, he has received a Thrust 2000 Fellowship in Engineering and is a trainee in the NSF-IGERT program in Cellular and Molecular Imaging for Diagnostics and Therapeutics. His current research focuses on the development of temperature-sensitive polymer nanoparticle systems for externally controlled drug delivery.

    Nicholas A. Peppas is the Fletcher S. Pratt Chair in Chemical Engineering, Biomedical Engineering, and Pharmacy, and is the director of the Center for Biomaterials, Drug Delivery and Bionanotechnology at the University of Texas at Austin. He is a member of the National Academy of Engineering, the Institute of Medicine of the National Academy of Sciences, the National Academy of Pharmacy of France and the Texas Academy of Engineering, Sciences and Medicine. He received his Diploma in Engineering (D. Eng.) from the National Technical University of Athens, Greece in 1971 and his Sc.D. from MIT in 1973, both in chemical engineering.

    View full text