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The rise and rise of drug delivery


Drug delivery has typically focused on optimizing marketed compounds, improving their effectiveness or tolerability, and simplifying their administration. This role now includes the first biopharmaceuticals as well as more conventional drugs. As drug-delivery technologies come into play earlier in the development cycle, however, they can also enhance the screening and evaluation of new compounds and 'rescue' failed compounds, such as those with low solubility. In this article, we look back at how the burgeoning field of drug delivery came into being and describe approaches for future discovery and development.

Timeline | Highlights of drug delivery discovery

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Figure 1: Systems approach to drug delivery.
Figure 2: Osmotic oral delivery systems.
Figure 3: Oral delivery.
Figure 4: Intracutaneous delivery.
Figure 5: Nanoparticles.


  1. 1

    Levy, G. Pharmacokinetics of salicylate elimination in man. J. Pharm. Sci. 54, 959–967 (1965).

    CAS  Article  Google Scholar 

  2. 2

    Prisant, L. M. & Elliott, W. J. Drug delivery systems for treatment of systemic hypertension. Clin. Pharmacokinet. 42, 931–940 (2003).

    CAS  Article  Google Scholar 

  3. 3

    Maggi, L., Bruni, R. & Conte, U. High molecular weight polyethylene oxides (PEOs) as an alternative to HPMC in controlled release dosage forms. Int. J. Pharm. 195, 229–238 (2000).

    CAS  Article  Google Scholar 

  4. 4

    Theeuwes, F. Elementary osmotic pump. J. Pharm. Sci. 64, 1987–1991 (1975).

    CAS  Article  Google Scholar 

  5. 5

    Theeuwes, F. et al. Elementary osmotic pump for indomethacin. J. Pharm. Sci. 72, 253–258 (1983).

    CAS  Article  Google Scholar 

  6. 6

    Anderson, R. et al. Once-a-day controlled release versus immediate release oxybutynin chloride in the treatment of urinary urge incontinence. J. Urol. 161, 1809–1812 (1999).

    CAS  Article  Google Scholar 

  7. 7

    Versi, E., Appell, R., Mobley, D., Patton, W. & Saltzstein, D. Dry mouth with conventional and controlled-release oxybutynin in urinary incontinence. Obstet. Gynecol. 95, 718–721 (2000).

    CAS  PubMed  Google Scholar 

  8. 8

    Swanson, J. et al. Development of a new once-a-day formulation of methylphenidate for the treatmentof attention-deficit/hyperactivity disorder: proof-of-concept and proof-of-product studies. Arch. Gen. Psychiatry 60, 204–211 (2003).

    CAS  Article  Google Scholar 

  9. 9

    Columbo, P. et al. Drug release modulation by physical restrictions of matrix swelling. Int. J. Pharm. 63, 43–48 (1990).

    Article  Google Scholar 

  10. 10

    Conte, U., Maggi, L., Colombo, P. & La Manna, A. Multi-layered hydrophilic matrices as constant release devices. J. Control. Release 26, 39–47 (1993).

    CAS  Article  Google Scholar 

  11. 11

    Conte, U., Colombo, P., Maggi, L. & La Manna, A. Compressed barrier layers for constant drug release in swellable matrix tablets. STP Pharm. Sci. 4, 107–113 (1994).

    CAS  Google Scholar 

  12. 12

    Conte, U. & Maggi, L. Modulation of the dissolution profiles from Geomatrix multi-layer matrix tablets containing drugs on different solubility. Biomaterials 17, 889–896 (1996).

    CAS  Article  Google Scholar 

  13. 13

    Biederman, J. et al. Efficacy and safety of Ritalin LA, a new, once daily, extended-release dosage form of methylphenidate, in children with attention deficit hyperactivity disorder. Paediatr Drugs. 5, 833–841 (2003).

    Article  Google Scholar 

  14. 14

    Semenchuk, M. R. Avinza élan. Curr. Opin. Investig. Drugs. 3, 1369–1372 (2002).

    CAS  PubMed  Google Scholar 

  15. 15

    Chourasia, M. K. & Jain, S. K. Design and development of multiparticulate system for targeted drug delivery to colon. Drug Deliv. 11, 201–207 (2004).

    CAS  Article  Google Scholar 

  16. 16

    Parojcic, J., Duric, Z., Jovanovic, M. & Ibric, S. An investigation into the factors influencing drug release from hydrophilic matrix tablets based on novel carbomer polymers. Drug Deliv. 11, 59–65 (2004).

    CAS  Article  Google Scholar 

  17. 17

    Viscusi, E. R., Reynolds, L., Chung, F., Atkinson, L. E. & Khanna, S. Patient-controlled transdermal fentanyl hydrochloride vs. intravenous morphine pump for postoperative pain. JAMA 291, 1333–1341 (2004).

    CAS  Article  Google Scholar 

  18. 18

    Prego, C., Garcia, M., Torres, D. & Alonso, M. J. Transmucosal macromolecular drug delivery. J. Control. Release 101, 151–162 (2005).

    CAS  Article  Google Scholar 

  19. 19

    Smith, J., Wood, E. & Dornish, M. Effect of chitosan on epithelial cell tight junctions. Pharm. Res. 21, 43–49 (2004).

    CAS  Article  Google Scholar 

  20. 20

    Eley, J. G., Pujari, V. D. & McLane, J. Poly (lactide-co-glycolide) nanoparticles containing coumarin-6 for suppository delivery: in vitro release profile and in vivo tissue distribution. Drug Deliv. 11, 255–261 (2004).

    CAS  Article  Google Scholar 

  21. 21

    Foran, T. M. New contraceptive choices across reproductive life. Med. J. Aust. 178, 616–620 (2003).

    PubMed  Google Scholar 

  22. 22

    Toivonen, J. The levonorgestrel-releasing uterine device. Adv Contracept Deliv Syst. 10, 191–198 (1994).

    CAS  PubMed  Google Scholar 

  23. 23

    Jain, S. K., Chourasia, M. K., Jain, A. K., Jain, R. K. & Shrivastava, A. K. Development and characterization of mucoadhesive microspheres bearing salbutamol for nasal delivery. Drug Deliv. 11, 113–122 (2004).

    CAS  Article  Google Scholar 

  24. 24

    Casez, J. P. et al. Effects of nasal calcitonin on bone mineral density following parathyroidectomy in patients with primary hyperparathyroidism. Horm. Res. 59, 263–269 (2003).

    CAS  PubMed  Google Scholar 

  25. 25

    Ayuk, J., Stewart, S. E., Stewart, P. M., Sheppard, M. C., European Sandostatin LAR Group. Efficacy of Sandostatin LAR (long–acting somatostatin analogue) is similar in patients with untreated acromegaly and in those previously treated with surgery and/or radiotherapy. Clin. Endocrinol. (Oxf) 60, 375–381 (2004).

    CAS  Article  Google Scholar 

  26. 26

    Attanasio, R. et al. Lanreotide 60 mg, a new long-acting formulation: effectiveness in the chronic treatment of acromegaly. J. Clin. Endocrinol. Metab. 88, 5258–5265 (2003).

    CAS  Article  Google Scholar 

  27. 27

    Fowler, J. E. Jr, Viadur Study Group. Patient-reported experience with the Viadur 12-month leuprolide implant for prostate cancer. Urology 58, 430–434 (2001).

    Article  Google Scholar 

  28. 28

    Fowler, J. E. et al. Evaluation of an implant that delivers leuprolide for 1 year for the palliative treatment of prostate cancer. Urology 55, 639–642 (2000).

    CAS  Article  Google Scholar 

  29. 29

    Fowler, J. E. Jr, Gottesman, J. E., Reid, C. F., Andriole, G. L. Jr & Soloway, M. S. Safety and efficacy of an implantable leuprolide delivery system in patients with advanced prostate cancer. J. Urol. 164, 730–734 (2000).

    CAS  Article  Google Scholar 

  30. 30

    Tam, C. S., Heersche, J. N., Murray, T. M. & Parsons, J. A. Parathyroid hormone stimulates the bone apposition rate independently of its resorptive action: differential effects of intermittent and continuous administration. Endocrinology 110, 506–512 (1982).

    CAS  Article  Google Scholar 

  31. 31

    Orskov, C., Wettergren, A. & Holst, J. J. Secretion of the incretin hormones glucagon-like peptide-1 and gastric inhibitory polypeptide correlates with insulin secretion in normal man throughout the day. Scand. J. Gastroenterol. 31, 665–670 (1996).

    CAS  Article  Google Scholar 

  32. 32

    Barry, B. W. Novel mechanisms and devices to enable successful transdermal drug delivery. Eur J. Pharm. Sci. 14, 101–114 (2001).

    CAS  Article  Google Scholar 

  33. 33

    Lee, W. R., Shen, S. C., Wang, K. H., Hu, C. H. & Fang, J. Y. The effect of laser treatment on skin to enhance and control transdermal delivery of 5-fluorouracil. J. Pharm. Sci. 91, 1613–1626 (2002).

    CAS  Article  Google Scholar 

  34. 34

    Shapiro, H., Harris, L., Hetzel, F. W. & Bar-Or, D. Laser assisted delivery of topical anesthesia for intramuscular needle insertion in adults. Lasers Surg. Med. 31, 252–256 (2002).

    Article  Google Scholar 

  35. 35

    Kaul, G. & Amiji, M. Long-circulating poly(ethylene glycol)-modified gelatin nanoparticles for intracellular delivery. Pharm. Res. 19, 1061–1067 (2002).

    CAS  Article  Google Scholar 

  36. 36

    Gabizon, A., Tzemach, D., Mak, L., Bronstein, M. & Horowitz, A. T. Dose dependency of pharmacokinetics and therapeutic efficacy of pegylated liposomal doxorubicin (DOXIL) in murine models. J. Drug Target 10 539–548 (2002).

    CAS  Article  Google Scholar 

  37. 37

    Theodoulou, M. & Hudis, C. Cardiac profiles of liposomal anthracyclines: greater cardiac safety versus conventional doxorubicin? Cancer 100, 2052–2063 (2004).

    CAS  Article  Google Scholar 

  38. 38

    Abra, R. M. et al. The next generation of liposome delivery systems: recent experience with tumor-targeted, sterically-stabilized immunoliposomes and active-loading gradients. J. Liposome Res. 12, 1–3 (2002).

    CAS  Article  Google Scholar 

  39. 39

    Fricker, G. & Miller, D. S. Modulation of drug transporters at the blood–brain barrier. Pharmacology 10, 169–176 (2004).

    Article  Google Scholar 

  40. 40

    LaVan, D. A., McGuire, T. & Langer, R. Small-scale systems for in vivo drug delivery. Nature Biotechnol. 21, 1184–1191 (2003).

    CAS  Article  Google Scholar 

  41. 41

    Rabinow, B. E. Nanosuspensions in drug delivery. Nature Rev. Drug Discov. 3, 785–796 (2004).

    CAS  Article  Google Scholar 

  42. 42

    Business Wire, January 12, 2005. Elan Corp. Elan's proprietary NanoCrystal Technology is used by Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&J PRD) in Phase III clinical trial of paliperidone palmitate [online], <> Press Release 12 Jan (2005).

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The authors wish to acknowledge J. Wright and D. Waxman for their help in preparing this manuscript.

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Competing interests

H.B.R. is a former employee of ALZA Corp. and continues to be a shareholder of Johnson & Johnson. T.A. is a former employee of Theratechnologies and continues to be a shareholder.

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Rosen, H., Abribat, T. The rise and rise of drug delivery. Nat Rev Drug Discov 4, 381–385 (2005).

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