DRUG DELIVERYAdvanced

Reviews

interviews

www.journals.elsevier.com/advanced-drug-delivery-reviews

For 25 years Advanced Drug Delivery Reviews has been the flagship journalfor review articles in drug delivery. The journal owes its success tocontributions of leading experts from around the world. The followinginterviews were conducted with prominent drug delivery scientists toprovide perspective, particularly to young investigators, on majoraccomplishments in the field to-date, and future directions in thisresearch area. I hope you enjoy reading these comments.

Sincerely,

Hamid Ghandehari, PhDEditor in ChiefAdvanced Drug Delivery Reviews

PREFACE

INTERVIEWS WITH:

Prof. Vincent Lee Prof. Suzie Pun Prof. Robert S. Langer Prof. Sarah Hamm-Alvarez Prof. Allan Hoffman

Prof. Nicholas A. Peppas Prof. Jindřich Kopeček Prof. Kazunori Kataoka Prof. Thomas Kissel Prof. Paula Hammond

What have been the majoraccomplishments in the field of drugdelivery in your view?

There are many. To me, the game-changingachievement is exponential rise in the qualityof drug delivery research. This is theconsequence of a paradigm shift in favor ofmultidisciplinary science -- the cornerstone ofdisruptive innovations necessary for managingthe molecular complexity of such diseases ascancer, diabetes, and neurodegeneration. Anumber of recent ADDR issues have done anexcellent job in illuminating the synergy thatwe can count on by engaging chemicalengineers, pharmaceutical scientists, molecularbiologists, mathematicians, and clinicians inseeking innovative solutions for solving drugdelivery challenges of the 21st century.

What should future scientists looktowards? What is around the curve, so to speak?

This is a very exciting time in the history ofdrug delivery research. We now have accessto a repertoire of tools and an array ofconcepts that never existed before. Theseadvances theoretically should enable thecreation of drug delivery systems for tacklingunmet medical needs. For example, we nowhave tools based on nano- and digitaltechnology to learn, in real time, where andhow quickly a drug delivery system isaccumulating in the body. If we may collectthat information from every user worldwideand if we may share that clinical informationwithin that community, wouldn’t we be in abetter position to refine the prototype drugdelivery platform and tailor it for a particularpatient with a unique genetic, life style, anddisease profile?

What is it in your area of research thatover the years has really excited you?

It is to learn firsthand how the courage andtenacity of my research team has led tocreative solutions for managing thecomplexity of age-related eye diseases and

for improving the safety of existing eyemedications. I found it exhilarating to let themomentum of research lead me to areas thatI never set out to investigate. I am particularlyproud of our contributions in advancing ourunderstanding of the ion transport and fluidtransport properties of the conjunctiva; itsactive transport capacity with respect topeptides, proteins, and nanoparticles; themolecular underpinning of alveolar epithelia indrug absorption; and the value ofcomputational chemistry to map themolecular configuration of the active site ofthe peptide transporter PepT1. These excitingmoments aside, we always remind ourselvesnot to lose sight of our social responsibility oftranslating our research into life-savingmedicine together with relevant advancesmade by other laboratories.

What role has the journal ADDRplayed in the past 2-3 decades, since its inception?

ADDR was founded 25 years ago by threehighly accomplished visionary scientists withcomplementary expertise – George Poste,Rudy Juliano, and Eric Tomlinson. Thislandmark scientific union has defined thecentral mission of ADDR as an influentialmultidisciplinary, global forum for teams ofexperts to showcase the latest advances indrug delivery and to spark debates andarouse interest in continuing the marathon ofadvanced drug delivery research. I believeADDR has been very effective in providingsuch a platform.

But we are living in a world of unprecedentedchange. I am confident that the editorialleadership team and its community ofpassionate contributors of ADDR will sustainits excellence by keeping pace with theavalanche of knowledge generated everyminute and with the alarming rate ofproliferation in social media that scientists ofthis generation are accustomed to in theirdaily interactions with other scientists in realtime whom they may not have met.

INTERVIEW WITH

Professor Vincent LeeSchool of Pharmacy, Chinese University of Hong Kong Former Editor-in-Chief of Advanced Drug Delivery Reviews (2001-2011)

“THIS IS A VERY EXCITING TIME IN THE HISTORY OFDRUG DELIVERY RESEARCH. WE NOW HAVE ACCESSTO A REPERTOIRE OF TOOLS AND AN ARRAY OF

CONCEPTS THAT NEVER EXISTED BEFORE.”

Can you tell us a little about yourresearch in drug delivery?

We are developing biomimetic materials fordrug delivery applications. Right now, we aredeveloping peptide-based polymers thatincorporate sequences to mimic how virusesinfect cells. We are applying these for genedelivery to the central nervous system. Weare also designing materials that willpreferentially affect cells involved in chronicinflammation to try to facilitate resolution atthose sites. Potential applications wouldinclude fibrosis or cancer.

What is it that excites you about drugdelivery?

There are a lot of diseases that are stilluntreatable or have suboptimal treatmentoptions so there is large room forimprovement and impact. I also just enjoyhow much there is to learn in this rapidlygrowing and evolving field.

What is your advice to the futuregeneration that will embark on drugdelivery?

It’s important to understand molecularly whatthe drug is doing, what happens to yourcarrier once it enters to living system andthen have an expertise that allows you tomanipulate this in vivo outcome to affect thedistribution of these drugs.

INTERVIEW WITH

Professor Suzie PunDepartment of Bioengineering, University of Washington

“JUST ENJOY HOW MUCH THERE IS TO LEARN INTHIS RAPIDLY GROWING AND EVOLVING FIELD.”

Could you introduce and tell us a littleabout yourself?

My name is Bob Langer and I am a Professorat the Massachusetts Institute of Technology(MIT) running a lab where a sizable part isdevoted to research on drug deliverysystems. I have been working in the drugdelivery field since 1974 and still think of it asa tremendously exciting field.

In your view what are the majoraccomplishments in the field of drug delivery?

I think the field of drug delivery has reallytransformed medical therapy. If I think back towhen I first started doing research, therewere hardly any advanced drug deliveryproducts on the market. Now, there are allkinds of products: transdermal patches,aerosols, implants, mircospheres, nanospheres.Such developments have totally changed thefield and I really believe it will continue toexpand its impact and change geneticmedicine as well.

How has advanced drug deliveryimpacted patients’ lives?

Well, I think somewhere between 30 to 100million patients a year use advanced drugdelivery systems, so it has had an enormousimpact on patient lives.

Are there any specific diseases wherepatients have particularly benefitedfrom advanced drug delivery systems?

There are just a tremendous number of drugdelivery systems that are transformingpatients’ lives. For example in prostate cancerthere are systems like Lupron Depot thathave really helped patients. Other examplesare schizophrenia with Risperdal Consta, andheart disease is sometimes treated with drug-eluting stents. The list just goes on and on.

What is the next upcoming area indrug delivery?

I think there are a variety of areas which willbe really important in the future; one isnanotechnology. It offers the excitingpossibility of not only targeting drugs right tospecific sites in the body, but also of deliveringDNA and siRNA. Another area which willcontinue to grow is non-invasive drugdelivery. This is an area where we are trying totake complex molecules like genes orproteins and deliver them without using aninvasive method.

I also think the area I like to call “smartdelivery systems” will have a big impact in thefuture. For example, developing a smartmicrochip that can actually sense molecularsignals in the body and deliver drugs inresponse could really transform the field.

What is your message to futurescientists who want to embark in this field?

Working in advanced drug delivery systems isan incredibly exciting area for young people.On the one hand there is really terrificscience and engineering research that will bedone, and on the other hand, there is theability to have a tremendous impact onhuman life and human health.

INTERVIEW WITH

Professor Robert S. LangerDepartment of Chemical Engineering, Massachusetts Institute of Technology

“THERE ARE JUST A TREMENDOUS NUMBER OFDRUG DELIVERY SYSTEMS THAT ARE TRANSFORMING

PATIENTS’ LIVES.”

What have been the majoraccomplishments in the field of drug delivery?

What has emerged over the past severalyears is the wonderful integration that wehave achieved thus far with chemists, physicists,engineers, biologists, informatics scientists aswell as physicians and pharmacists into a trueinterdisciplinary and translationally-focusedscientific discipline. We are so much furtherthan we were when I entered this field abouttwenty years ago, in terms of really trying tointegrate the fabrication of delivery vehiclesand diverse cargo including proteins andDNA/RNA with the ability to specificallytarget this payload to a particular place in thebody. The explosion of “omics” areas such asproteomics and genomics have provided awealth of information on the identification ofunique features of diseased tissue that are ripefor integration into targeted delivery systems.

What is your specific interest in thefield of drug delivery that reallyinterests you and intrigues you tocontinue in this field?

So my specific interest has always been in thearea of cellular trafficking pathways, specificallyidentifying receptor and uptake pathways thatare unique to target tissues that are affectedby diseases or overexpressed in diseasedtissue, and try to figure out how we mayspecifically exploit those uptake pathways tofacilitate and target to those tissues. Thatmeans that I am involved in the very basicscientific aspects of endocytosis, intracellularsorting of materials and receptor biology, andI am pleased to see that much of this field hasevolved to address translationally-focusedproblems such as targeted drug delivery. So Iwould say that my continued interest andchallenge in the field is really trying tointegrate the basic discovery with the appliedsciences in the area of drug delivery.

What is your advice to futurescientists getting into the field of drugdelivery and what are some of theemerging areas that you can see?

So I think that my advice to scientists who liketo enter the drug delivery area includes reallytrying to cultivate a truly interdisciplinaryapproach to research early on, so no matterwhat kind of PhD program you are in, really tryto take course work and to attend seminarsthat are slightly outside of your major sphere ofinterest so that you can begin to adopt relevanttools from outside your core discipline intoyour science. As well pay attention totranslational research training opportunitieswhich can include ways in which your preclinicalwork can become more translationally focusedand ways in which you may tailor yourcommunications skills to engage with multiplecollaborators in different worlds(pharmaceutical companies, biotechnologycompanies) since the science of the future willrequire engagement on many fronts. It is alwayscritical to hone your written and oralcommunications skills and I would takeadvantage of any writing and communicationsopportunities that come your way. These skillsare essential in any field. From a scientificperspective, I would also say in terms of recentimpact in the field, I think the impact of imagingtechnology and in particular the integration ofsystems which both detect and treat diseases inthe form of theranostics will really continue tobe a hot area in the next ten years.

What do you think has been theimpact of the journal Advanced DrugDelivery Reviews in the field?

I think the journal is obviously the premierreview journal in the field and I personally relyon this journal for my graduate and Pharm Dteaching. I routinely assign the articles whichreflect state of the art advances in the field tomy students, postdoctoral fellows, we readthem in our journal club, and we rely on themas we then plan our advances and our nextsteps and our next grant applications.

INTERVIEW WITH

Professor Sarah Hamm-AlvarezSchool of Pharmacy, University of Southern California

“I THINK THE IMPACT OF IMAGING TECHNOLOGYAND IN PARTICULAR THE INTEGRATION OF SYSTEMS

WHICH BOTH DETECT AND TREAT DISEASES IN THE

FORM OF THERANOSTICS WILL REALLY CONTINUE

TO BE A HOT AREA IN THE NEXT TENYEARS.”

What should the general readers ofADDR know about this field?

I think anybody who is working in this fieldshould have some idea about the variousroutes of drug delivery to the body. Theyshould also have a good understanding of“ADME”, that is, the absorption, distribution,metabolism and elimination of drugs withinthe body. In addition, they should know aboutthe various sites where drugs can act withinthe body, e.g. in the tissues, in the circulation, atcell membranes and within the cell.

How and when did the field ofAdvanced drug delivery originate?

I think it really started about 55 years agowith Judah Folkman at Harvard whoproposed the drugs could be encapsulated insilicone rubber capsules and implanted in thebody for controlled release of the drug, andAlex Zaffaroni in California, who founded acompany dedicated to the controlled deliveryof drugs into and within the body. He calledthe company Alza.

What have been the majoraccomplishments in the field of drug delivery?

Many “smart” controlled release systems havebeen designed and clinically applied over thepast 50 years. They include oral enteric-coated drug tablets, drug-loaded capsules asmucosal inserts, tubular capsules assubcutaneous implants, injected degradablepolymer-drug mixtures, surface-immobilizeddrugs, and topical skin patches. The early drugdelivery systems (DDS) have been macro-and micro-scale devices, while more recentlythe trend has been to develop the verysmallest delivery systems, nanocarriers. Thereare many diverse nano-scale drug deliverysystems that are being developed today. Theseare very exciting and novel delivery systemsand they are now gradually increasing inclinical use. Why are soluble drugnanocarriers so interesting? They canaccumulate in solid tumors due to the EPR

effect, they can avoid the first pass effect andthey can also avoid the P-glycoprotein effluxand multi-drug resistance of some cancer cells.

Where do you think this field is headed?

The drug delivery field is becoming more andmore biological and less and less materials-oriented. The materials used in DDS arepretty well understood, but the biology is stilla big black box. There is much to learn in theareas of cell biology and DNA and the effectsof drugs on a specific patient’s body. Predictingthe effects of drugs and their combinations onindividual patients will be a big focus in thefuture, as the fields of pharmacogenomics andpersonalized medicine grow.

What inspired you to embark on this field?

I really liked the interdisciplinary combinationof so many fields of science; it was veryappealing to me. The drug delivery fieldcombines polymeric materials, their synthesisand their degradation, molecular diffusion ofdrugs and metabolites, chemical and biologicalreactions, and the fundamentals of cell biology.It’s everything you want to know in onepackage.

What is your own area of expertiseand how are you excited about it?

I am a polymer materials scientist/engineerand I am most excited by the ability tocontrol the synthesis of polymers in theirvarious forms, eg, block copolymers, graftcopolymers, star polymers and dendrimers,using RAFT and ATRP controlled free radicalpolymerization techniques. All of thesemethods have come about in the last 10-15years and this has been very exciting time fora polymer chemist and materials scientistworking in the field of biomaterials.

INTERVIEW WITH

Allan Hoffman, Professor EmeritusDepartment of Bioengineering, University of Washington

PHYSICAL MATERIALS ARE FAIRLYWELL UNDERSTOODCOMPAREDTO BIOLOGICAL MATERIALS. BIOLOGY ISSTILL A BIG BLACK BOX, BUT ASWE IMPROVE OURUNDERSTANDING OF DNA AND CELLS, NEW ANDIMPROVED “BIO-SMART” DRUG DELIVERY SYSTEMSWILL BE DEVELOPED.

What has been the majoraccomplishment of the field of drugdelivery over the past few decades?

The main accomplishment has been the abilityto design a new series of systems, devices andformulations that improve the quality of life ofour patients. This development can take thepatients from the simple everyday use of aparticular medicine or a variety of medicines toa more advanced level where they will begiven a particular drug only at specific times, aformulation that will work very well for theparticular application. So, this has been really amajor success. At the same time, the reductionof cost of health care in the United States andthe world is part of the drug delivery success.

What about success of the field inspecific therapeutic areas?

Going back to the historical systems if youwish, we can imagine what a great “liberation” itwas for patients to use the pilocarpine ALZAsystems once a day instead of having to takeeye drops for glaucoma treatment four times aday! This was a huge development. This deliverysystem (Ocusert ®) worked for quite a fewyears, it was eventually withdrawn from themarket for a number of reasons, but it was anexample of how things could be done.

So what do you think are going to bethe most exciting future advances inthe field of drug delivery? What shouldthe young people look for and focus onfor the field to move forward?

It is a very difficult question to answer, becausethere are two aspects of that question. One iswhat is scientifically satisfying- what the younggeneration of academic and industrial scientistsare going to be pursuing in their research andtrying to solve. There are many problems thatneed to be answered. But the most importantpoint we have to understand is that the field ofdrug delivery does not work in a vacuum. Itworks in a society, where we have to pay forthe health care expense, where we have torecognize that the pharmaceutical companies

are under a tremendous pressure to deliver,and to deliver with profit in a market wherethe generics have become extremelyimportant.

So when scientists say they want to work on anew polymer carrier that will improve GIabsorption, they have to understand, and theydon’t necessary understand, that such newpolymers are very expensive to test andproduce and that the present regulatory andbusiness system does not allow for suchpolymers to be used immediately. Again, thisgoes back to a question of financial and politicalquestions that have to be answered, and at thesame time to the need to develop betterdevices, better systems or better treatments.Having said that I think the pharmaceuticalindustry is under tremendous pressure. Theycannot continue to work and develop newtablets or capsules, simply because the addedvalue of such pharmaceutical products isextremely low. And of course, as you know,many of these systems are now being made inother countries not in the United States, andare sold here as generic products.

I believe our young generation of scientistsshould address questions related to majordiseases that are causes of death right now inthe United States and the world and come upwith better solutions, more cost effective andperhaps better for the patients. So for me“cancer treatment” would be the number onechoice. Really developing techniques that willprovide therapy to patients by treating thespecific sites, the specific cells.

I also believe that diabetes treatment hasnumerous problems that are unsolved. Weexpect that by the year 2025 about 25% of theAmerican population will suffer from diabetes.We need to answer this problem; the solutionmay not be simply an injection. We may haveto need to come up with better drugs andbetter administration methods. So I think theseare areas which need to be answered.

INTERVIEW WITH

Professor Nicholas A. PeppasDepartments of Biomedical Engineering, Chemical Engineering and College of Pharmacy, The University of Texas at Austin

“I BELIEVE THAT DIABETES HAS A LOT OF PROBLEMSTHAT ARE UNSOLVED. WE EXPECT THAT BY THEYEAR 2025 ABOUT 25% OF THE AMERICANPOPULATIONWILL HAVE DIABETES.”

What have been the majoraccomplishments in the field of drug delivery?

The commercial success of Luprolide wasimportant; it demonstrated the potential ofsustained drug delivery systems. Polymer-modified proteins have shown the potential ofwater-soluble polymers in the design of efficienttherapeutics. My laboratory focuses on water-soluble polymer – drug conjugates. Numerousconjugates have been in clinical trials and thereis a clear understanding what needs to be donefor the wide application of bioconjugates in theclinics. Last but no least, the development ofnew non-invasive imaging techniquescontributed to the efficient design ofnanomedicines.

Speaking about the future, what are the areas you see as emerging in thefield of drug delivery?

I certainly hope that in the near future water-soluble bioconjugates will reach the clinics.Several new developments indicate that thisgoal is achievable. Examples of importantadvances include the development of backbonedegradable multiblock polymeric carriers ofanticancer drugs and the design ofmacromolecular therapeutics based on a newconcept – apoptosis induction initiated bycrosslinking of cell surface receptors mediatedby the biorecognition of two coiled-coil formingpeptides. The latter approach is called drug-freemacromolecular therapeutics since no lowmolecular weight drugs are involved.

I hope that there will be a breakthrough in theDNA/RNA delivery. I guess a totally newdesign of non-viral carriers is needed to achievea high degree of transfection and expression.

What do you think has been thecontribution of the journal AdvancedDrug Delivery Reviews in this field?

It is a very important journal; interdisciplinaryfields such as drug delivery need a forumwhere researchers may receive informationfrom top scientists with different backgrounds.Such knowledge is crucial for the successfuldesign of new approaches to solve importantproblems in life sciences.

Finally, a good journal such as Advanced DrugDelivery Reviews might help to attract youngscientists into active research in drug delivery. Itis a great research area and I strongly advocateit. If asked what else to recommend to youngscientists, here is the answer: Work hard; don’ttry to just modify the research topic of yourmentor, choose a new direction; major factorsfor your success are persistence, curiosity, goodanalytical skills, communications skills, the abilityto listen to advice, work easily with others, donot change after success, and lead yourcolleagues by example and not by force.

INTERVIEW WITH

Professor Jindřich KopečekDepartment of Pharmaceutics and Pharmaceutical Chemistry & Department of Bioengineering , University of Utah

“...LISTEN TO ADVICE, WORK EASILY WITH OTHERS,DO NOT CHANGE AFTER SUCCESS AND LEADYOUR

COLLEAGUES BY EXAMPLE AND NOT BY FORCE.”

What have been the majoraccomplishments in the field of drug delivery?

For a long time, people used to think drugdelivery was just a science fiction. It was really onlyPaul Ehrlich who thought about Salvarsan(arfsenamine).

When I was a high school boy, the US created theApollo aircraft in order to send a human to themoon. By utilizing a very small nano-scale carriersystem we have realized our dream of sendingdrugs, genes or any other substances into thedesired part in the body. Today, we have manycarrier systems and targeting moieties. So I thinkthat we can say the nano-carrier system has beenthe Apollo to the micro cosmos of our body.

You have worked a lot with blockcopolymer micelles over the years. What do you think is special about blockcopolymer micelles in drug delivery?

There are many advantages, but from a polymerscience view point, as you may know, if you putthese block copolymers into an aqueous solution,they spontaneously self-assemble into very distinctcompartments. By utilizing block copolymers wecan get very well-defined nanocompartments andof course these nanocompartments can beutilized for the delivery of drugs. Other segmentscan work to increase the solubility and stericproperties and then maybe we can attach somesimilar responsive segments. So, by conjugating thefunctional segments in tandem, we can reachmany nanoscale compartments.

I know you have many of these blockcopolymer micelle drugs in clinical trials.At what stage do you think these willactually be used in real patients?

Now, all different formulations of block copolymermicelles are either in phase 1 or phase 2 clinicaltrials. The most advanced one is micelle loadedwith paclitaxel, that has just completed the phasetwo study and is in preparation for phase 3.Usually, phase three clinical studies take severalyears to complete but we will know more inroughly two or three years.

What do you think will be the actualbenefit for the patients? How will cancerpatients benefit from it?

By utilizing this kind of drug delivery system,there will be a decrease in patient’s side effects.Also, we recently found out this kind of system isquite effective for the treatment of parietal cellcancer. It is also quite effective for the treatmentof metastases and for the treatment of drugresistant tumors. So we are finding out that withthis kind of system, we can treat patients whosuffer from intractable tumors.

What is your advice for futuregenerations of drug delivery scientists?

Let’s see, one thing especially with regards totargeting, is that the main focus is on cancertumors and that will be a major topic in thefuture. Also, we need to develop and preparecarrier systems which cross the blood brainbarrier and hopefully treat other diseases forexample Alzheimer’s or Parkinson’s; that shouldbe fantastic.

Also, we are finding that we can prepare verywell organized carrier systems and add someimaging agents so that they become ananocarrier that can be utilized for imaging. Thatwould, of course, be an advantage for the clinicbut would also have a big impact onfundamental biology.

How do you think Advance DrugDelivery Reviews has played a role in the development of this science?

ADDR is very important as a reviews journal forthe community of drug delivery. However, as Imentioned before, the delivery of biologicalcompounds to the desired site is quite useful forfundamental biologists and I also know thatmany people in the chemistry field are veryinterested in drug delivery, so the journal isbecoming relevant beyond the community ofdrug delivery scientists.

INTERVIEW WITH

Professor Kazunori KataokaDepartment of Materials Science, University of Tokyo

“SO NOW I THINKWE CAN SEND THE DRUG,GENE OR ANY OTHER SUBSTANCES INTO THE

DESIRED PART IN THE BODY BY UTILIZING A VERY

SMALL NANO-SCALE CARRIER SYSTEM....”

What have been the milestones andchallenges in the field of drug delivery?

In the 70’s the concept emerged thatpharmacokinetics, physiology and also materialsscience have to work together and this wasproven with the scopolamine patch. It is a veryinteresting example because this “drug” wasused as an ointment as far back as the middleages, but didn’t find its way into treatmentbecause it was too toxic. Modulating therelease from the polymer devices, in the sense“the flatter the better”, really achievedsomething of value for treatment of motionsickness. This was expanded very rapidly intoother things like parenteral delivery systemsand osmotic systems. If you define success ascommercial success, these were tremendouslysuccessful products, blockbusters in a sense andI think this was the side of the drug deliveryfield which attracted a lot of people.

Now, after this initial success it became morecomplicated. Again, we have a blockbuster, apeptide, Lupron, but the success could notgenerally be extended to proteins. This hasbeen one of the biggest disappointments. I stillthink this is an area for future research asyoung people getting into this field have anample playing ground for a lot of differentproteins, growth factors and antibodies- youname it - that could be beneficially delivered bythe use of polymeric systems.

Looking further ahead there is still a bigchallenge, an area of unmet needs; Gene andsiRNA delivery. Despite 10 years or even moreof intensive research there has not really beena break through. I think the concepts we haveabout biology, the body, how things get intocells and how we can reach diseased tissues ina very specific way is something whereprobably a lot of progress still has to be made ifyou want to translate it into clinical success.

Being of “the older generation” you also startto get worried about central nervous systemdiseases such as Alzheimer’s. Another famouschallenge waiting for the young generation isthe blood brain barrier which still doesn’t havea real efficient delivery system. Again, this is anarea where you can make a lot of progress.

What is the cutting edge research indrug delivery today?

I still believe nanotechnology is an area thatremains cutting edge. It is interesting because itpulls in a different set of researchers, those notso familiarized with drug delivery, such as thephysics and imaging departments. It isextremely attractive to build multimodality intonano-delivery systems allowing imaging,targeting, and possibly triggered release.

Also, I think the area of gene and siRNAdelivery particularly when it translates intoclinically relevant areas is very relevant. This isthe secret of drug delivery in my opinion,having a multidisciplinary platform technology.From the very start, it was not specifically justfor the pharmacy department or just for thechemistry department; you had to pulleverything together to make it happen. This isthe true challenge (and attractiveness) of drug delivery!

What has been the impact of Advanced Drug Delivery Reviews(ADDR) in the field?

There are a number of journals in thepharmacy field and the attractiveness ofAdvanced Drug Delivery Reviews, in mypersonal opinion, is the thematic issues. You geta more balanced view from having not just onearticle, but different opinions from differentexperts in one subject area.

The second thing I like about ADDR is the mixbetween biology and material sciences. Toeducate people in chemistry about biology isdifficult and vice versa. So to have a platformwhere both things are explained to therespective areas is really the true value of ADDR.

INTERVIEW WITH

Professor Thomas KisselDepartment of Pharmaceutics & Biopharmaceutics, Philipps-Universität Marburg

“NOW IF YOU LOOK FURTHER AHEAD, I THINKTHERE IS A BIG CHALLENGE AND I THINK THAT ISAN AREA OF UNMET NEEDS AND THIS IS GENE

AND SIRNA DELIVERY AND I THINK DESPITE 10YEARS OF INTENSIVE RESEARCH OR EVEN MORE....”

What do you think are the majoraccomplishments in the field of drugdelivery over the past 3 or 4 decades?

In the past three or four decades, I think wehave made a huge amount of advancementtowards delivering oligonucleotides, DNA,siRNA and we are already seeing the impactof those developments. I think that we havealso come a very long way in terms ofdesigning systems that can actually get to thetumour, but we still have a long way in termsof going beyond just getting into the cell. Wehave to get therapeutics out of theendosome and to the intracellularcomponents that are relevant for a giventherapy – RNAi to the RISC complex, andDNA to the nucleus for example.Intracellular trafficking is really needed totarget different kinds of therapeutic strategies.

What are the things that really exciteyou in the field of drug delivery and inthe research that you are doing?

What really excites me is the ability tounderstand more about how cell biologyworks and using that as a way to leveragedrug delivery. For example being able tounderstand what types of ligands work, whatkinds of environments are present in tumoursor infectious disease that we can takeadvantage of to trigger drug release. Soresponsive material systems get me excited,being able to use them as a way to deliverdrugs gets me very excited.

What are the new upcoming areas ofdrug delivery research that youngerscientists should pay attention to?

Younger scientists should be aware of thekinds of tools that have been introduced to usnow. We have heard about new imaging tools,new ways of being able to combine imagingand targeting together. New ways ofintroducing physical stimuli such as ultrasoundand temperature that can actually triggerrelease under certain conditions. Youngpeople have to be aware of that.

Young people need to be able to learn thelanguage of biology. They need to be able totalk to cell biologists, they need to be able totalk to pharmacologists, they need to reallyunderstand pharmacokinetics, because thereare a number of barriers we are experiencingnow. These barriers include the fact that wecan design something extremely clever thatworks in vitro, but once we try to get it intothe body we can’t get it to circulate over thetime periods that we need, or to accumulatein the target organs versus filtration organslike the liver. We also can’t get the release wewant at the desired times in many cases, andfor multicomponent release systems, wecannot always control loading, timing andsequence of release.

What do you think has been theimpact of ADDR in the field?

In my view ADDR has been really crucial. Iactually entered this field coming from a basicpolymer science background. Being able topull down articles that gave me a review ofthe field and some perspective, and also someadvice on where things are going wasincredibly important for me as I began tolaunch into this area. I know it’s incrediblyimportant for my colleagues, and now that Iam in the field, I actually use these reviews asways to determine where the pulse is, tounderstand what is going on now.

INTERVIEW WITH

Professor Paula HammondDepartment of Chemical Engineering, Massachusetts Institute of Technology

“YOUNG PEOPLE NEED TO BE ABLE TO LEARN THELANGUAGE OF BIOLOGY. THEY NEED TO BE ABLE TOTALK TO CELL BIOLOGISTS, THEY NEED TO BE ABLETO TALK TO PHARMACOLOGISTS, THEY NEED TOREALLY UNDERSTAND PHARMACOKINETICS.”