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.
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Levy, G. Pharmacokinetics of salicylate elimination in man. J. Pharm. Sci. 54, 959–967 (1965).
Prisant, L. M. & Elliott, W. J. Drug delivery systems for treatment of systemic hypertension. Clin. Pharmacokinet. 42, 931–940 (2003).
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).
Theeuwes, F. Elementary osmotic pump. J. Pharm. Sci. 64, 1987–1991 (1975).
Theeuwes, F. et al. Elementary osmotic pump for indomethacin. J. Pharm. Sci. 72, 253–258 (1983).
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).
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).
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).
Columbo, P. et al. Drug release modulation by physical restrictions of matrix swelling. Int. J. Pharm. 63, 43–48 (1990).
Conte, U., Maggi, L., Colombo, P. & La Manna, A. Multi-layered hydrophilic matrices as constant release devices. J. Control. Release 26, 39–47 (1993).
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).
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).
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).
Semenchuk, M. R. Avinza élan. Curr. Opin. Investig. Drugs. 3, 1369–1372 (2002).
Chourasia, M. K. & Jain, S. K. Design and development of multiparticulate system for targeted drug delivery to colon. Drug Deliv. 11, 201–207 (2004).
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).
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).
Prego, C., Garcia, M., Torres, D. & Alonso, M. J. Transmucosal macromolecular drug delivery. J. Control. Release 101, 151–162 (2005).
Smith, J., Wood, E. & Dornish, M. Effect of chitosan on epithelial cell tight junctions. Pharm. Res. 21, 43–49 (2004).
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).
Foran, T. M. New contraceptive choices across reproductive life. Med. J. Aust. 178, 616–620 (2003).
Toivonen, J. The levonorgestrel-releasing uterine device. Adv Contracept Deliv Syst. 10, 191–198 (1994).
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).
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).
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).
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).
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).
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).
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).
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).
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).
Barry, B. W. Novel mechanisms and devices to enable successful transdermal drug delivery. Eur J. Pharm. Sci. 14, 101–114 (2001).
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).
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).
Kaul, G. & Amiji, M. Long-circulating poly(ethylene glycol)-modified gelatin nanoparticles for intracellular delivery. Pharm. Res. 19, 1061–1067 (2002).
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).
Theodoulou, M. & Hudis, C. Cardiac profiles of liposomal anthracyclines: greater cardiac safety versus conventional doxorubicin? Cancer 100, 2052–2063 (2004).
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).
Fricker, G. & Miller, D. S. Modulation of drug transporters at the blood–brain barrier. Pharmacology 10, 169–176 (2004).
LaVan, D. A., McGuire, T. & Langer, R. Small-scale systems for in vivo drug delivery. Nature Biotechnol. 21, 1184–1191 (2003).
Rabinow, B. E. Nanosuspensions in drug delivery. Nature Rev. Drug Discov. 3, 785–796 (2004).
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], <http://www.elan.com/DrugDelivery/Announcements/12_01_2005.asp> Press Release 12 Jan (2005).
The authors wish to acknowledge J. Wright and D. Waxman for their help in preparing this manuscript.
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). https://doi.org/10.1038/nrd1721
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