Drug-Delivery Technology is Needed
Why IsTechnology For Effective Drug Delivery Still Not Available?
Jun 23, 2009
Creating new, more effective medicines using biotechnology products such as proteins, DNA and RNA needs enabling technology that can get these compounds to their site of action. It is Paul Ehrlich who is credited with the vision of “magic bullets” - compounds designed with specific features capable of treating specific diseases while “leaving all else alone”. His concept certainly captured the imagination and minds of scientists and inventors over the last 100 years – however, “magic” has not happened yet. While the future advanced therapies depend on it, effective technology to deliver drugs to their putative disease targets is not available.
Publications versus Progress
A PubMed database literature search for the period from 2000 up to January 31, 2009 using “drug delivery” search term produces some 20,646 “hits”, 5,806 of these being reviews (giving a ratio of 1 review for every 3.6 original publications). The search term “nanoparticle” gives for the same period 21,297 “hits”. Many of these publications conclude that the technology being reported shows a “great promise” for the future but as yet no therapeutically effective site-specific drug delivery systems are available.
Why this lack of progress?
Why is it that after years of research and tens of thousands of publications, little progress has been made? The principle reason is the lack of understanding on the part of the researchers of what requirements of the biological system need to be satisfied, and even more the lack of attention to meeting these basic demands. Doing the same thing and expecting different results is often described as lunacy. A recent review by Whitehead et al. [Whitehead KA, Langer R, Anderson DG. Knocking down barriers: advances in siRNA delivery. Nat Rev Drug Discov. 2009 Feb;8(2):129-38] places its hopes on materials that “failed to deliver” many times before, such as cyclodextrin,
polyethyleneimine, “dynamic PolyConjugates”, oligofectamine, liposomes, etc. An Expert Opinion review by Aneja et al. [Aneja MK, Geiger J-P, Himmel A and Rudolph C. targeted gene delivery to the lung. Expert Opin. Drug Deliv. (2009) 6(6) 567-83] concluded that “…although targeted gene delivery …has been demonstrated…, the clinical translation of this know-how still needs to be attained”.
Old ideas with new names?
Quite often, old ideas are given new names, like calling small particles “nanomaterials”,
somehow hoping that this will “solve the problem”. Statement such as “Their small size and readily modifiable chemical and physical properties make them attractive for protecting and transporting payloads…” as stated by Yamanaka et al. (2008) [Yamanaka YJ, Leong KW. Engineering strategies to enhance nanoparticle-mediated oral delivery.
J Biomater Sci Polym Ed. 2008;19(12):1549-70] does nothing to address the essential problems of delivery.
Meeting this challenge must start with understanding fully what is “allowed by biology”.
Relevant properties of new materials can easily be tested in vitro as shown for example by Artursson et al. [Artursson P and O’Mullane J. Cellular and biochemical interactions of macromolecular drug delivery systems. Advanced Drug Delivery Reviews volume 3, No. 2 (Editor K. Petrak) (March-April 1989) 165-190]. Materials that fail such early
tests should not be pursued further. Further, ability of a new system to interact
specifically with its target can easily be tested easily in vitro, and so can the drug attachment to the carrier and its release. In any case, it is unethical to use live animals in testing to answer questions that can be answered by other means. Only the systems that show in vitro all the relevant properties should be considered for testing in vivo.
It as self-evident that in developing “biomaterials” one must take into full recognition all the pertinent features of the biological system. A lack of progress in developing site-selective and other drug-delivery systems suggests that this is not always the case in practice.
