Editorial

A Personal Reflection on the Career of the 2004 Life-timeAchievement Award Winner

R.L. JULIANO*

Department of Pharmacology, 1017 Mary Ellen Jones Building, University of North Carolina, Chapel Hill, North Carolina, USA

I would like to start by thanking Saghir Akhtar, the Editor

of the Journal of Drug Targeting, for initiating this

special issue of the journal. I would also like to thank

those who contributed articles, including many friends,

colleagues and former trainees. I am deeply touched and

honored by your efforts. Although I have worked in the

field of drug delivery for many years, I do feel that there

are others who are much more deserving of this honor

than I am. Nonetheless I am very gratified and I will try to

do my part by providing a brief and very personal account

of my association with drug targeting and delivery

research.

I started off years ago as a recently minted Ph.D.

biophysicist interested in membrane structure. At that time

Alec Bangham had just described liposomes, phospholipid

bilayer vesicles that could serve as model membranes.

As a postdoctoral fellow at Roswell Park Memorial

Institute in Buffalo NY, I interacted with Dimitri

Papahadjopoulos (regrettably now deceased) one of the

pioneers in the liposome area. I was also influenced from

afar by the work of Gregory Gregoriadis in the UK, who

was advocating the use of liposomes as a drug delivery

system. When I started my own laboratory at the Hospital

for Sick Children in Toronto in 1972, I still considered

myself to be a membrane biochemist/biophysicist.

However, I plunged into studies of liposomes as drug

delivery agents, with one of our first efforts being an

evaluation of how particle size and charge affected the

in vivo clearance behavior of liposomes. Surprisingly this

very basic question had not yet been explored. Other

studies followed concerning how liposome encapsulation

could affect the kinetics and biodistribution of anti-cancer

drugs. By this time I was beginning to think of myself

more and more as a drug delivery investigator. I decided

that I wanted to learn more about the overall field, since

up to that point the only aspect that I knew about was

liposomes.

The opportunity came during a move to the Department of

Pharmacology at the University of Texas Medical School in

Houston. While I was waiting anxiously to hear whether my

first NIH grants would be funded, I undertook editing a

volume (Drug Delivery Systems, Oxford University Press,

1980) that included chapters on many different areas

including polymeric delivery systems, transdermal delivery,

and other topics. This task introduced me to some of the

excellent work on the physical and chemical aspects of drug

delivery that was taking place at that time. Among the key

contributors in this area were Tak Higuchi (now deceased)

ISSN 1061-186X print/ISSN 1029-2330 online q 2004 Taylor & Francis Ltd

DOI: 10.1080/10611860400000631

*Tel.: þ1-919-966-4383. E-mail: arjay@med.unc.edu

Journal of Drug Targeting, July 2004 Vol. 12 (6), pp. 313–314

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and his many talented colleagues at the University of

Kansas. Although I was still primarily a biologist, I was very

impressed by the their work on the physical pharmacy and

pharmacokinetics of delivery systems. However, just as

I needed to learn more about the physical aspects of drug

delivery it also seemed clear that the physical pharmacists

needed to learn more about the biology of the problem.

One approach to this was a lengthy review article that

I co-authored with Marc Poznansky (Pharmacol. Reviews

36: 277–336, 1984). In that review we elaborated the

concept of biological barriers to drug delivery, including the

reticuloendothelial system, the capillary wall, the extra-

cellular matrix and others. Not that these ideas were

completely novel, but I do believe that the review article

presented them in an integrated and coherent manner and

thus had an impact on the field.

While I was in Houston our work on liposomal drug

delivery continued. I was fortunate to find some excellent

colleagues, particularly Gabriel Lopez-Berestein,

Roy Hopfer (now deceased), Kapil and Reeta Mehta and

later Sayed Daoud. It was Gabe Lopez who first raised the

issue of using liposomes to deliver the antifungal

antibiotic amphotericin B. Our team worked on this for

several years, eventually laying the groundwork for

the development of one of the forms of liposomal

amphotericin that is currently used in the clinic.

The late 1980s saw the development of the first wave

of commercially successful liposomal drugs. At that

time there were several strong academic laboratories

active in liposome research including those of Dimitri

Paphadjopoulos, Frank Szoka, Leaf Huang, Terry Allan,

Pieter Cullis, Gerritt Scherphof and others. In addition,

there were many fine scientists at the several liposome-

based biotech companies that had come into being. All of

this effort has resulted in at least a half dozen liposomal

drugs currently in clinical use. Of particular interest,

so-called “Stealth” liposomes, with long circulation times,

embodied many of the current ideas regarding overcoming

biological barriers to drug delivery.

In 1987, I moved to the Department of Pharmacology at

the University of North Carolina. At that point I decided to

leave liposome research and take up something new.

I became intrigued by the potential of antisense

oligonucleotides as highly selective therapeutic agents,

but also realized that there were important delivery issues

to be addressed. With the collaboration with my young

colleagues Saghir Akhtar, Yoko Shoji and Jeff Hughes we

investigated the transport of antisense oligonucleotides

by cells and tissues, and their interactions with artificial

membranes (back to liposomes!). In additional work

we also examined in vivo and hepatic clearance of

oligonucleotides (with Arno Nolting). Over the last few

years a major emphasis has been developing strategies to

enhance the intracellular delivery of antisense. One

approach has been to use polycationic dendrimers as a

delivery agent; this tactic was explored by Rob DeLong

and Hoon Yoo of our laboratory. Another very successful

approach has been the use of antisense coupled to “cell

penetrating peptides”. This was initiated by Anna Astriab-

Fisher and is being continued by Hyunmin Kang.

I have been very pleased to witness the recent evolution

of the drug delivery/drug targeting field. A cohort of

talented young investigators has been attracted to this

sophisticated, dynamic, and important area. Moreover,

there is far less of a schism between the biologists and the

physical scientists in the field. It seems that it is now

generally recognized that creative work on the physical

and chemical aspects of delivery formulations must be

coupled with an insightful approach to the biology of the

system. I think this attitude is reflected in the several

excellent articles contained in this volume. They range

from very basic studies regarding the design and synthesis

of novel liposomes and novel oligonucleotides, to studies

of the kinetics of delivery systems, to very new applica-

tions in the delivery of nutraceuticals and agents used in

orthopedics. Thus I look forward to reading these and

many more interesting and exciting articles in the Journal

of Drug Targeting.

EDITORIAL314

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