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News Round-up

Nanopa r t i c l e s S h own to be

E f f e c t i v e A g a i n s t B r e a s t

C an c e r

Recent findings published in the Journal of

Molecular Pharmaceutics suggest that the

administration of nanoparticles is helping in

the fight against breast cancer. The

University of Pennsylvania-based team

demonstrated that biodegradable nano-

particles containing two potent cancer-

fighting drugs are effective in killing human

breast tumours. The unique properties ofthe hollow shell nano-particles, known as

polymersomes, allow them to deliver two

distinct drugs, paclitaxel and doxorubicin,

directly to tumours implanted in mice.

The properties of these polymersomes are

manipulated to ferry their drug combi-

nation to the tumour. The large polymers

making up the shell allow water-insoluble

paclitaxel to embed within the shell, while

doxorubicin, which is water-soluble, stays

within the interior of the polymersomeuntil it degrades.

Dennis Discher, a professor in Penns

School of Engineering and Applied Science

and a member of Penns newly established

Institute for Translational Medicine and

Therapeutics commented that the system

provides a number of advantages over other

Trojan horse-style drug delivery systems,

and should prove a useful tool in fighting a

number of diseases.

The lead author of the study, and a fellow

at Harvard Medical School, Fariyal

Ahmed, added: recent studies have shown

that cocktails of paclitaxel and doxorubicin

lead to better tumour regression than

either drug alone, but there hasnt been

any carrier system that can carry both drugs

as efficiently to a tumour. Polymersomes

get around those limitations.

This research was supported by grants from

the US National Institutes of Health (NIH),

the National Science Foundation (NSF)

Materials Research Science and Engineering

Center and the Nanotechnology Institute.

T a r g e t ed D ru g D e l i v e r y

B r eak th rou gh

A peptide that can specifically and

directly deliver molecules to the inside of

cells like a nanosyringe has been

developed by Yale and the University ofRhode Island scientists, creating a new

tool for drug delivery, gene control and

tissue imaging.

The cargo carrier peptide, named pH

(low) insertion peptide (pHLIP),

accumulates in the membranes of cells in

acidic environments and spontaneously

transfers attached molecules across the

membrane. The cargo is then released by

cleavage of a sulphursulphur bond that is

only unstable if it is inside the cell.

The study, published in the Proceedings of the

National Academy of Sciences USA, shows that

pHLIP entry into the cell membrane and

the translocation of molecules into cells are

not mediated by the usual entry pathways

endocytosis, interactions with cell receptors,or by formation of pores in cell membranes.

pHLIP may provide a new approach for

imaging, diagnosis and treatment of diseases

with naturally occurring or artificially

created low-pH extracellular environments,

12 F U T U R E D R U G D E L I V E R Y 2 0 0 6

The Drug De l ive ry Arena In Br ie f

An Authori t a t i ve Round-up o f T r ends , S t a t i st i c s and C l i n i ca l Re s ea r ch

1. Robin A L, Landry T, Bergamini M V W, Clark A F, A single anterior juxtascleral anecortave acetate injection lowers intraocular pressure greater than

3 months in patients with open angle glaucoma, Program and Abstracts of the Association for Research in Vision and Ophthalmology , April30May 4, 2006; Fort Lauderdale, Florida. Abstract 1541.

2. Lee V, Harnessing nanotechnology for ocular drug delivery, Program and Abstracts of the Association for Research in Vision and

Ophthalmology, April 30May 4, 2006; Fort Lauderdale, Florida. Abstract 2339.

0

5

10

15

20

25

2002 2004 2006 2008 2010 2012

0

50%

100%

150%

200%

250%

Growth$US Billions

Figure 1: Drug Delivery Technologies Market Value and Annual Growth Rate

0

2002 2004 2006 2008

20

40

60

80

100

120

0

2%

4%

6%

8%

10%

12%$US Billions Growth

Figure 2: Injectable Drug Delivery Market Value and Value Forecasts

Source: Based on data from Jain PharmaBiotech

Source: Based on data from Datamonitor

7/30/2019 The Drug Delivery Arena In Brief

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News Round-up

such as tumours, infarcts, stroke-afflicted

tissue, atherosclerotic lesions, sites of

inflammation or infection, or damagedtissue resulting from trauma, commented

Donald Engelman, professor of molecular

biophysics and biochemistry at Yale

University. He added: Our system offers a

new technology for the fast and efficient

delivery of drugs, imaging probes, or cell

and gene regulation agents into living cells.

I n j e c t ab l e and P ro t e i n

De l i v e r y Ma rk e t s S e t t o G row

Both the injectable drug delivery and proteintherapeutic markets are forecast to grow

even further. Already both markets have

shown a huge increase in sales and

investments, and this trend is expected to

continue, with compound annual growth

rates of 10% to the year 2008 for the

injectable delivery market, and 10.5% to

2010, almost double the value in the protein

therapeutic market. These marked increases

are due to the increasing use of

reformulation techniques earlier in product

life-cycles, which is changing the dynamicsof the injectables field, and the increased use,

development and discovery of protein

therapeutics.

Improv i n g G l au c oma D ru g

De l i v e r y S y s t ems

In a recent annual meeting of the

Association for Research in Vision and

Ophthalmology (ARVO), the important

topic of novel systems for the delivery ofglaucoma medications was highlighted. A

review of current topical delivery revealed

that current drop therapy has caused side

effects including increased incidence of

cataract and of heart attacks due to elevated

cholesterol from beta-blocker use. As such,

several alternatives to this traditional

therapy were discussed. Robin1 spoke

about juxtascleral injection of an analogue

of cortisol known as anecortave acetate.

Lee2 of the US Food and Drug

Administration (FDA) spoke aboutharnessing nanotechnology in ocular drug

delivery systems.

The appeals of nanotechnology include

the ability to access specialised

transportation systems of the body and

thus achieve high local levels of drug, and

the possibility of providing

pharmacologic intelligence on the effects

of a drug. Dowdy3 of the Howard Hughes

Medical Institute spoke of the potential of

short interfering RNAs (siRNAs) inocular pharmacology of the future, and

Tao, Chief Scientific Officer of

Neurotech,4 discussed a new modality

that would involve the encapsulation of

mammalian cells genetically modified to

secrete a desired substance within a

membrane-bound structure that is then

introduced into the eye.

Dru g D e l i v e r y S y s t em Con t ro l s

A r t e r i a l P r e s su r e , C a rd i a c

Ou tpu t and L e f t H ea r tF i l l i n g P r e s su r e

Japanese researchers have developed a

novel automated drug delivery system for

simultaneous control of systemic arterial

pressure (AP), cardiac output (CO), and

left atrial pressure (Pla).5 Uemura and

colleagues at the National Cardiovascular

Research Institute in Suita explained:

Previous systems attempted to directly

control AP and CO by estimating their

responses to drug infusions. This approachis inapplicable because of the difficulties of

estimating simultaneous AP, CO and Pla

responses to the infusion of multiple drugs.

The circulatory equilibrium framework

developed previously indicates that AP,

CO and Pla are determined by an

equilibrium of the pumping ability of the

left heart, stressed blood volume and

systemic arterial resistance.

Umura futher explains: Our system directly

controls the pumping ability of the left heartwith dobutamine, the stressed blood volume

with dextran/furosemide, and systemic

arterial resistance with nitroprusside, thereby

controlling the three variables. By directly

controlling the mechanical determinants of

circulation, our system has enabled

simultaneous control of AP, CO and Pla

with good accuracy and stability.

F U T U R E D R U G D E L I V E R Y 2 0 0 6 13

3. Dowdy S, Can we deliver siRNA efficiently into cells?, Program and Abstracts of the Association for Research in Vision and Ophthalmology,

April 30May 4, 2006; Fort Lauderdale, Florida. Abstract 2340.

4. Tao W, Application of encapsulated cell technology for treating ophthalmic diseases, Program and Abstracts of the Association for Research inVision and Ophthalmology, April 30May 4, 2006; Fort Lauderdale, Florida. Abstract 2341.

5. Uemura K, Kamiya A, Hidaka I et al., Automated drug delivery system to control systemic arterial pressure, cardiac output, and left heart filling pressure

in acute decompensated heart failure,J Appl Physiol, 2006;100(4): pp. 1,2781,286.

0

2003 2008

10

20

30

40

Market Value ($US Billions)

Sustained release

(oral, injectable, topical)

Transdermal drug

delivery systems

Transmucosal

delivery systems

Implants and IUDs

Targeted drug

delivery systems

Other

Figure 3: Advanced Drug Delivery Systems: New Developments and Technologies,

Market Value and Value Forecast

Sustained release (oral,

injectable topical) 51%

Implants and IUDs 2%

Transdermal drug

delivery systems 6%

Targeted drug

delivery systems 19%

Transmucosal drug

delivery systems 22%

Figure 4: Drug Delivery New Technologies

Market 2005

Source: Business Communications Company Source: Based on data from Business Communications Company