The process of developing an old drug for new indications is now a widely accepted strategy of shortening drug development time, reducing drug costs, and improving drug availability, especially for rare and neglected diseases. In this mini-review, we highlighted the impact of drug delivery systems in the fulfillment of crucial aspects of drug repurposing such as (i) maximizing the repurposed drug effects on a new target, (ii) minimizing off-target effects, (iii) modulating the release profiles of drug at the site of absorption, (iv) modulating the pharmacokinetics/in vivo biodistribution of the repurposed drug, (v) targeting/modulating drug retention at the sites of action, and (vi) providing a suitable platform for therapeutic application of combination drugs.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Adams CP, Brantner VV. Estimating the cost of new drug development: is it really $802 million? Health Aff. 2006;25(2):420–8.
Hahn K. Old drugs are new again, vol. 566. Plainsboro, NJ: Intellisphere, LLC; 2011.
DiMasi JA, Feldman L, Seckler A, Wilson A. Trends in risks associated with new drug development: success rates for investigational drugs. Clin Pharmacol Ther. 2010;87(3):272–7.
Li YY, Jones SJ. Drug repositioning for personalized medicine. Genome Med. 2012;4(3):27.
Sleigh SH, Barton CL. Repurposing strategies for therapeutics. Pharm Med. 2010;24(3):151–9.
Cragg GM, Grothaus PG, Newman DJ. New horizons for old drugs and drug leads. J Nat Prod. 2014;77(3):703–23.
Napolitano F, Zhao Y, Moreira VM, Tagliaferri R, Kere J, D’Amato M, et al. Drug repositioning: a machine-learning approach through data integration. Journal of Cheminform. 2013;5(1):30.
Merino A, Bronowska AK, Jackson DB, Cahill DJ. Drug profiling: knowing where it hits. Drug Discov Today. 2010;15(17):749–56.
Sciences NCfAT. Early-Stage Repurposing [Webpage]. 6701 Democracy Boulevard, Bethesda MD 20892–4874: US Department of Health and Human Services; 2018 [updated 8–20-18. Available from: https://ncats.nih.gov/preclinical/repurpose/early. Accessed 22 June 2018.
Yeh CT, Wu AT, Chang PM, Chen KY, Yang CN, Yang SC, et al. Trifluoperazine, an antipsychotic agent, inhibits cancer stem cell growth and overcomes drug resistance of lung cancer. Am J Respir Crit Care Med. 2012;186(11):1180–8.
Oliva CR, Zhang W, Langford C, Suto MJ, Griguer CE. Repositioning chlorpromazine for treating chemoresistant glioma through the inhibition of cytochrome c oxidase bearing the COX4-1 regulatory subunit. Oncotarget. 2017;8(23):37568–83.
Zhang C, Gong P, Liu P, Zhou N, Zhou Y, Wang Y. Thioridazine elicits potent antitumor effects in colorectal cancer stem cells. Oncol Rep. 2017;37(2):1168–74.
Arber N, Eagle CJ, Spicak J, Racz I, Dite P, Hajer J, et al. Celecoxib for the prevention of colorectal adenomatous polyps. N Engl J Med. 2006;355(9):885–95.
Tranfaglia MR, Thibodeaux C, Mason DJ, Brown D, Roberts I, Smith R, et al. Repurposing available drugs for neurodevelopmental disorders: the fragile X experience. Neuropharmacology. 2018. https://doi.org/10.1016/j.neuropharm.2018.05.004.
Leigh MJ, Nguyen DV, Mu Y, Winarni TI, Schneider A, Chechi T, et al. A randomized double-blind, placebo-controlled trial of minocycline in children and adolescents with fragile X syndrome. J Dev Behav Pediatr JDBP. 2013;34(3):147–55.
Nagaoka A, Takehara H, Hayashi-Takagi A, Noguchi J, Ishii K, Shirai F, et al. Abnormal intrinsic dynamics of dendritic spines in a fragile X syndrome mouse model in vivo. Sci Rep. 2016;6:26651.
Ming X, Mulvey M, Mohanty S, Patel V. Safety and efficacy of clonidine and clonidine extended-release in the treatment of children and adolescents with attention deficit and hyperactivity disorders. Adolesc Health Med Ther. 2011;2:105–12.
Cipriani P, Ruscitti P, Carubbi F, Liakouli V, Giacomelli R. Methotrexate: an old new drug in autoimmune disease. Expert Rev Clin Immunol. 2014;10(11):1519–30.
Taherian E, Rao A, Malemud CJ, Askari AD. The biological and clinical activity of anti-malarial drugs in autoimmune disorders. Curr Rheumatol Rev. 2013;9(1):45–62.
Liao JK, Laufs U. Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol. 2005;45:89–118.
Jaromin A, Zarnowski R, Pietka-Ottlik M, Andes DR, Gubernator J. Topical delivery of ebselen encapsulated in biopolymeric nanocapsules: drug repurposing enhanced antifungal activity. Nanomedicine (London, England). 2018;13(10):1139–55.
Nagai N, Yoshioka C, Mano Y, Tnabe W, Ito Y, Okamoto N, et al. A nanoparticle formulation of disulfiram prolongs corneal residence time of the drug and reduces intraocular pressure. Exp Eye Res. 2015;132:115–23.
Deguchi S, Otake H, Nakazawa Y, Hiramatsu N, Yamamoto N, Nagai N. Ophthalmic formulation containing nilvadipine nanoparticles prevents retinal dysfunction in rats injected with streptozotocin. Int J Mol Sci. 2017;18(12):2720.
Mylonaki I, Strano F, Deglise S, Allemann E, Alonso F, Corpataux JM, et al. Perivascular sustained release of atorvastatin from a hydrogel-microparticle delivery system decreases intimal hyperplasia. J Controll Release. 2016;232:93–102.
Gupta N, Al-Saikhan FI, Patel B, Rashid J, Ahsan F. Fasudil and SOD packaged in peptide-studded-liposomes: properties, pharmacokinetics and ex-vivo targeting to isolated perfused rat lungs. Int J Pharm. 2015;488(1–2):33–43.
Rostamkalaei SS, Akbari J, Saeedi M, Morteza-Semnani K, Nokhodchi A. Topical gel of metformin solid lipid nanoparticles: a hopeful promise as a dermal delivery system. Colloids Surf B: Biointerfaces. 2018;175:150–7.
Brooks AM, Gillies WE. Ocular beta-blockers in glaucoma management. Clinical pharmacological aspects. Drugs Aging. 1992;2(3):208–21.
Vanderveen EE, Ellis CN, Kang S, Case P, Headington JT, Voorhees JJ, et al. Topical minoxidil for hair regrowth. J Am Acad Dermatol. 1984;11(3):416–21.
Marcus S. Beyond repurposing: the case for creating new chemical entities by modifying existing molecules: Genetic Engineering and Biotechnology News August 28, 2017 [Available from: https://www.genengnews.com/gen-exclusives/beyond-repurposing-the-case-for-creating-new-chemical-entities-by-modifying-existing-molecules/77900970. Accessed 22 June 2018.
Kovacsovics TJ, Mims A, Salama ME, Pantin J, Rao N, Kosak KM, et al. Combination of the low anticoagulant heparin CX-01 with chemotherapy for the treatment of acute myeloid leukemia. Blood Adv. 2018;2(4):381–9.
Gama N, Kumar K, Ekengard E, Haukka M, Darkwa J, Nordlander E, et al. Gold(I) complex of 1,1′-bis(diphenylphosphino) ferrocene-quinoline conjugate: a virostatic agent against HIV-1. Biometals. 2016;29(3):389–97.
Bonelli P, Tuccillo FM, Federico A, Napolitano M, Borrelli A, Melisi D, et al. Ibuprofen delivered by poly(lactic-co-glycolic acid) (PLGA) nanoparticles to human gastric cancer cells exerts antiproliferative activity at very low concentrations. Int J Nanomedicine. 2012;7:5683–91.
da Silveira EF, Chassot JM, Teixeira FC, Azambuja JH, Debom G, Beira FT, et al. Ketoprofen-loaded polymeric nanocapsules selectively inhibit cancer cell growth in vitro and in preclinical model of glioblastoma multiforme. Investig New Drugs. 2013;31(6):1424–35.
Venkatesan P, Puvvada N, Dash R, Prashanth Kumar BN, Sarkar D, Azab B, et al. The potential of celecoxib-loaded hydroxyapatite-chitosan nanocomposite for the treatment of colon cancer. Biomaterials. 2011;32(15):3794–806.
Marques JG, Gaspar VM, Costa E, Paquete CM, Correia IJ. Synthesis and characterization of micelles as carriers of non-steroidal anti-inflammatory drugs (NSAID) for application in breast cancer therapy. Colloids Surf B: Biointerfaces. 2014;113:375–83.
Lu Z, Long Y, Cun X, Wang X, Li J, Mei L, et al. A size-shrinkable nanoparticle-based combined anti-tumor and anti-inflammatory strategy for enhanced cancer therapy. Nanoscale. 2018;10(21):9957–70.
Paulmurugan R, Bhethanabotla R, Mishra K, Devulapally R, Foygel K, Sekar TV, et al. Folate receptor-targeted polymeric micellar nanocarriers for delivery of orlistat as a repurposed drug against triple-negative breast cancer. Mol Cancer Ther. 2016;15(2):221–31.
Eskinazi-Budge A, Manickavasagam D, Czech T, Novak K, Kunzler J, Oyewumi MO. Preparation of emulsifying wax/GMO nanoparticles and evaluation as a delivery system for repurposing simvastatin in bone regeneration. Drug Dev Ind Pharm. 2018;44(10)1583–90.
Naito Y, Terukina T, Galli S, Kozai Y, Vandeweghe S, Tagami T, et al. The effect of simvastatin-loaded polymeric microspheres in a critical size bone defect in the rabbit calvaria. Int J Pharm. 2014;461(1–2):157–62.
Matbou Riahi M, Sahebkar A, Sadri K, Nikoofal-Sahlabadi S, Jaafari MR. Stable and sustained release liposomal formulations of celecoxib: in vitro and in vivo anti-tumor evaluation. Int J Pharm. 2018;540(1–2):89–97.
Jin M, Shen X, Zhao C, Qin X, Liu H, Huang L, et al. In vivo study of effects of artesunate nanoliposomes on human hepatocellular carcinoma xenografts in nude mice. Drug Deliv. 2013;20(3–4):127–33.
Agarwal NB, Jain S, Nagpal D, Agarwal NK, Mediratta PK, Sharma KK. Liposomal formulation of curcumin attenuates seizures in different experimental models of epilepsy in mice. Fundam Clin Pharmacol. 2013;27(2):169–72.
Xiao Y, Wang S, Zong Q, Yin Z. Co-delivery of metformin and paclitaxel via folate-modified pH-sensitive micelles for enhanced anti-tumor efficacy. AAPS PharmSciTech. 2018;19(5)2395–406.
Xu P, Yu H, Zhang Z, Meng Q, Sun H, Chen X, et al. Hydrogen-bonded and reduction-responsive micelles loading atorvastatin for therapy of breast cancer metastasis. Biomaterials. 2014;35(26):7574–87.
Andalib S, Molhemazar P, Danafar H. In vitro and in vivo delivery of atorvastatin: a comparative study of anti-inflammatory activity of atorvastatin loaded copolymeric micelles. J Biomater Appl. 2018;32(8):1127–38.
McDonald BF, Quinn AM, Devers T, Cullen A, Coulter IS, Marison IW, et al. In-vitro characterisation of a novel celecoxib microbead formulation for the treatment and prevention of colorectal cancer. J Pharm Pharmacol. 2015;67(5):685–95.
Hill EE, Kim JK, Jung Y, Neeley CK, Pienta KJ, Taichman RS, et al. Integrin alpha V beta 3 targeted dendrimer-rapamycin conjugate reduces fibroblast-mediated prostate tumor progression and metastasis. J Cell Biochem. 2018;119:8074–83.
El-Moslemany RM, Eissa MM, Ramadan AA, El-Khordagui LK, El-Azzouni MZ. Miltefosine lipid nanocapsules: intersection of drug repurposing and nanotechnology for single dose oral treatment of pre-patent schistosomiasis mansoni. Acta Trop. 2016;159:142–8.
Roney C, Kulkarni P, Arora V, Antich P, Bonte F, Wu A, et al. Targeted nanoparticles for drug delivery through the blood-brain barrier for Alzheimer’s disease. J Controll Release. 2005;108(2–3):193–214.
Nath SD, Linh NT, Sadiasa A, Lee BT. Encapsulation of simvastatin in PLGA microspheres loaded into hydrogel loaded BCP porous spongy scaffold as a controlled drug delivery system for bone tissue regeneration. J Biomater Appl. 2014;28(8):1151–63.
Thapa RK, Nguyen HT, Jeong J-H, Kim JR, Choi H-G, Yong CS, et al. Progressive slowdown/prevention of cellular senescence by CD9-targeted delivery of rapamycin using lactose-wrapped calcium carbonate nanoparticles. Sci Rep. 2017;7:43299.
The authors are grateful to Thomases Family Endowment and Dr. Colene Young Memorial Fund. Dharani Manickavasagam helped with literature compilation.
Conflict of Interest
The authors declare that they have no conflict of interest.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Guest Editors: Mahavir Bhupal Chougule, Vijaykumar B. Sutariya and Sudip K. Das
About this article
Cite this article
Czech, T., Lalani, R. & Oyewumi, M.O. Delivery Systems as Vital Tools in Drug Repurposing. AAPS PharmSciTech 20, 116 (2019). https://doi.org/10.1208/s12249-019-1333-z
- drug delivery systems
- drug development
- combination drugs