NANOTECHNOLOGY IN DRUG DELIVERY

DR. POOJA ROYDEPARTMENT OF PHARMACOLOGY,

VIMS & RC, BANGALORE

OUTLINE

need for new delivery systems Definition – nanotechnology Definition - nanomedicine Nanomedicineso Nanoporeso Quantum dotso Fullereneso Nanoshellso Dendrimerso Nanorobots

Need for New Drug Delivery Systems

Introducing a new drug to market costs on an average US $ 897 million / 4485 crores

Process for approval may take upto 15 yrs

Already existing time tested drugs are effectively used by interdisciplinary approaches to increase their efficacy

Its Advantages..

To improve the drug delivery i.e. increases drug bioavailability in required zone

Prevent / minimize harmful side effects

Minimize drug degradation and loss

Prolonged duration of drug action

For better patient compliance

Routes of Administration

ORAL

SUBLINGUAL

RECTAL

INHALATION

PARENTERAL .

NEWER DELIVERY SYSTEMS

Ocusert , Progestasert Liposomes , Polymer based drug delivery system Insulin pen , Insulin pump

Transdermal drug delivery system , Prodrugs

Nanomedicines (Nanotechnology)

Iontophoresis , phonophoresis

Computerized miniature pumps , Monoclonal antibodies

NANOTECHNOLOGY & NANOMEDICINE

Breakthroughs in HealthcareEnabled by Nanotechnology

BIGGER ISN’T ALWAYS BETTER

- SIR RICHARD FEYNMAN (1959)

HISTORY

Richard Feynman – 1959 lecture at California Institute of Technology

Title : There is plenty of

room at the bottom (the idea of building objects from the bottom up, i.e. from individual atoms )

HISTORY

Mid 1980s: Eric Drexler (1986)-

published Engines of Creation.

Envisioned a molecular nanotechnology discipline – allow to fabricate products from the bottom up and allows every molecule to be inserted into its specific place

NATIONAL NANOTECHNOLOGY INITIATIVE - DEFINITION

R & D at atomic, molecular and macromolecular levels in sub-100 nm range (1 to 100 nm).

COMPARISON OF SIZES

(WITH LIVING SYSTEM)

THE IMAGINARY WORLD OF NANOMEDICINE!

NANOMEDICINE

Monitoring, repair, construction, and control of human biological systems at the molecular level, using engineered nanodevices and nanostructures

NANOTECHNOLOGY AND NANOMEDICINE

NANOTECHNOLOGY NANOMEDICINE Science dealing with

nanoparticles.

E.g.- nanodevices like Q-dots, dendrimers widespread and broadly marketed.

Established discipline

Clinical application of this science to the practice of medicine.

Yet to find their way into clinical devices.

Nascent stage of development

Characteristics of Nanoparticles

Target specificity Extreme small size Encapsulation efficiency Carry high concentrated drug Zeta potential (surface charge) Efficient drug release

NANOPORES

Tiny cell containing chambers within single crystalline silicon wafers

Chambers interface with surrounding biological environment

Present high density of pores

NANOPORES

Pores large enough to allow passage of small molecules like – insulin, glucose and oxygen

Pores not large enough to permit immune system molecules – Ig’s, graft borne virus particle

Thus immunosuppressants not required

EXAMPLES OF NANOPORES

Immunoisolated encapsulated rat pancreatic cells

Microcapsules containing isolated islets of Langerhans cells, can be implanted beneath skin of diabetic patients

Similarly can be used to replenish any enzyme or hormone deficiency conditions

NANOPORES IN FUTURE

In neurodegenerative disorders like Alzheimer’s disease and Parkinsonism.

Encapsulated neurons placed in brain

Things Used so far..

Fluorescent tags

Used in HIV test, in experiments to image the inner functions of cells

Limitations – 1) Different dyes for different colour2) Colour matched lasers for each dye to

fluoresce3) Dye colours fade quickly after one use

The New Era..

QUANTUM DOTS

Colour defined by particle size and composition.

Linked to biomolecules to form long lived sensitive probes to –

a) Identify specific compoundsb) To track biological events

Structure and application of Quantum (Q dots) dots

FULLERENES Form of C-60 composed of C-atoms arranged in a

soccer ball like configuration

Also called bucky balls

Ideal drug delivery vehicles due to their size and shape

Good bioavailability , low toxicity even at high dosages

Is it fullerenes or soccer balls?

USES OF FULLERENES

As anti-viral agents (e.g.- HIV)

Anti-tumor and anti-cancer therapy.

Anti-oxidants

Anti-apoptotic agents (e.g.- Parkinson’s disease)

NANOSHELLS Developed at Rice University in Houston

Platform for nanoscale drug delivery

Di-electric metal nanospheres with a core of silica and a golden coating

Each slightly larger than polio virus

GOLD NANOSHELLS

Gold Nanoparticle

NANOSHELLS IN CIRCULATION

MECHANISM OF ACTION OF NANOSHELLS

Consist of drug containing tumour-targeted hydrogel polymer injected into the body

Shells accumulate near the tumour

Heated by IR laser, polymer melts and releases drug at the desired site

Nanoshell Delivery causes Cancer Cell Death

Nanospectra Biosciences

At University of Texas, developing commercial applications of nanoshells

Animal studies carried out to specifically target micro-metastasis

CANCER SMART BOMBS

FDA approved targeted radioimmunotherapeutic agents

Deliver radioactive Yttrium or Iodine to lymphoma directed antibody (anti CD-20 antibody).

NANOGENERATOR

Alpha emitting actinium based ,use internalizing monoclonal antibodies to penetrate the cell.

Useful in – leukaemia lymphoma breast CA Ovarian CA Neuroblastoma

DENDRIMER BASED DEVICES

Tree like synthetic nanostructured particle with branches emanating out.

Branches act as hooks to which important molecules like DNA can be attached.

Enters cells by endocytosis.

DENDRIMERS

TECTO - DENDRIMERS

Single core dendrimer surrounded by additional dendrimer modules of different types

Ethylene diamine core surrounded by folic acid, fluorescein, and methotrexate

100 fold improvement in cytotoxic response to methotrexate

GENOMIC REVOLUTION

At least one unique protein has been identified in half dozen cancers

As genomic revolution progresses, mostly proteins unique to each type of cancer will be identified

Dendrimers will target these proteins

GENOMIC REVOLUTION

LIPID BASED DRUGS First nanodrugs to be used

Phospholipids chemically

ABRAXANE – used for metastatic breast cancer A formulation of anti-cancer drug Paclitaxel with

micro-fine albumin

Advantages Capable of paclitaxel delivery to the body at a

50% higher dose over 30 mins Avoids toxic effects.

CONTD….

Paclitaxel , due to its poor solubility in blood,if given bound with various solvents can cause hypersensitivity reactions

This may neccesitate of steroids administration

which may in turn cause Hyperglycemia Immunosuppression Insomnia

Multicomponent Targeting Strategies

NANOROBOTS

Has carbon nanotube body, biomolecular motor that propels it and peptide limbs to orient itself

in vivo use

NANOROBOTS

Used for – Targeted drug delivery Taking biopsies Reopening of blocked arteries

Magnetically controlled karyobots and cytobots to perform wireless intracellular surgery

CARDIOVASCULAR NANOMEDICINE

FDA approved nano-cardio

products not available

May help in preventing blood vessel occlusion by thrombi (detects even small thrombi)

NEUROLOGICAL NANOMEDICINE

Repair of CNS following trauma

Critical target To be able to take brain biopsy to

detect beta amyloid plaques (currently possible only after death at autopsy) in Alzheimer’s disease

ONCOLOGY AND NANOMEDICINE

Advantages over conventional cancer therapy ---

higher payload capacity increased blood circulation times improved anti-tumor efficacy reduced toxicity to healthy tissues

ONGOING CLINICAL TRIALS

Nanoparticles in ophthalmology (Retina implants, age-related macular

degeneration, glaucoma)

Nanoparticles in OA and inflammatory arthritis

NANOMEDICINE AND FUTURE

More medical benefits in next 10 yrs

Exhaustive research both in India and abroad

Government granting huge funds

REFERENCES

C A Haberzettl. Nanomedicine: destination or journey?.INSTITUTE OF PHYSICS PUBLISHING NANOTECHNOLOGYNanotechnology 13 (2002) R9–R13.

K. John Morrow, Jr, RajBawa, Chiming Wei. Recent Advances in Basic and Clinical Nanomedicine. Med Clin N Am 91 (2007) 805–843.

Robert A. Freitas, Jr. Current Status of Nanomedicine and Medical Nanorobotics. Journal of Computational and Theoretical Nanoscience Vol.2, 1–25, 2005.

REFERENCES

ELVIN BLANCO, CHASE W. KESSINGER, BARAN D. SUMER, JINMING GAO. Multifunctional Micellar Nanomedicine for Cancer Therapy. 2009 by the Society for Experimental Biology and Medicine.

S. MoeinMoghimi, A. Christy Hunter, and J. Clifford Murray. Nanomedicine: current status and future prospects. The FASEB Journal. 0892-6638/05/0019-0311.

Volker Wagner, AnwynDullaart, Anne-Katrin Bock & Axel Zweck. The emerging nanomedicine landscape. NATURE BIOTECHNOLOGY VOLUME 24 NUMBER 10 OCTOBER 2006.

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