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Significance and strategies in develo** delivery systems for bio-macromolecular drugs

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Abstract

Successful development of a new drug is prohibitively expensive, and is estimated to cost approximately $100—500 million US dollars for a single clinical drug. Yet, a newly developed drug can only enjoy its patent protection for 18 years, meaning that after this protected time period, any company can manufacture this product and thus the profit generated by this drug entity would reduce dramatically. Most critically, once a drug is being synthesized, its physical, chemical, and biological attributes such as bioavailability and in vivo pharmacokinetics are all completely fixed and cannot be changed. In principal and practice, only the application of an appropriately designed drug delivery system (DDS) is able to overcome such limitations, and yet the cost of develo** a novel drug delivery system is less than 10% of that of develo** a new drug. Because of these reasons, the new trend in pharmaceutical development has already begun to shift from the single direction of develo** new drugs in the past to a combined mode of develo** both new drugs and innovative drug delivery systems in this century. Hence, for develo** countries with relatively limited financial resources, a smart strategic move would be to focus on the development of new DDS, which has a significantly higher benefit/risk ratio when comparing to the development of a new drug.

Because of the unmatched reaction efficiency and a repetitive action mode, the therapeutic activity of a single bio-macromolecular drug (e.g., protein toxins, gene products, etc.) is equivalent to about 106–108 of that from a conventional small molecule anti-cancer agent (e.g., doxorubicin). Hence, bio-macromolecular drugs have been recognized around the world as the future “drug-ofchoice”. Yet, among the >10000 drugs that are currently available, only ∼150 of them belong to these biomacromolecular drugs (an exceedingly low 1.2%), reflecting the difficulties of utilizing these agents in clinical practice. In general, the bottleneck limitations of these biomacromolecular drugs are two-fold: (1) the absence of a preferential action of the drug on tumor cells as opposed to normal tissues, and (2) the lack of ability to cross the tumor cell membrane. In this review, we provide strategies of how to solve these problems simultaneously and collectively via the development of innovative drug delivery systems. Since worldwide progress on bio-macromolecular therapeutics still remains in the infant stage and thus open for an equal-ground competition, we wish that this review would echo the desire to industrialized countries such as China to set up its strategic plan on develo** delivery systems for these bio-macromolecular drugs, thereby realizing their clinical potential.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Avbor, MI, 48109-1065, USA

    Huining He, Meong Cheol Shin, Kyuri Lee & Victor Yang

  2. Tian** Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tian** Medical University, Tian**, 300072, China

    Huining He, Qiuling Liang & Victor Yang

  3. State Key Laboratory for Chemical Engineering, School of Chemical Engineering and Technology, Tian** University, Tian**, 300072, China

    Junbo Gong, Junxiao Ye, Quan Liu & **gkang Wang

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  1. Huining He
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He, H., Liang, Q., Shin, M.C. et al. Significance and strategies in develo** delivery systems for bio-macromolecular drugs. Front. Chem. Sci. Eng. 7, 496–507 (2013). https://doi.org/10.1007/s11705-013-1362-1

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