Detailed idea on nanotechnology, nanomedicine, types, uses, pharmacotherapy, and future prospects of the nanotechnology. Drug delivery systems, Pharmacokinetics and pharmacodynamics of the nanoparticles are dealt in detail

1. Dr. Siddhartha Dutta
Mamc
New Delhi

2. Introduction
Nanotechnology
Engineered Nano- Materials
PK of ENM
Types of ENM
Approved ENMs & ENMs under clinical
investigation
Future prospects

3.  “Nanos” means DWARF
 One-billionth part of something
 “Nanoscience: Involves research and technology development
at nanoscale(0.1 nm to 100nm range)”
 NIH started in the year 2000 the National Nanotechnology
Initiative

5.  Nanoporous ceramic filters were indeed already being used in
the19th century to separate viruses
 1902 structures smaller than 4 nanometers were successfully
detected in ruby glasses using the ultra microscope developed
by Richard Zsigmondy
 Proposed by Richard Feynman in his book titled
“There’s Plenty of Room at the Bottom”
 Why cannot we write the
entire 24 volumes of the
Encyclopedia Britannica on the head of a pin?”

6.  The understanding and control of matter at dimensions
between approximately 1 and 100 nanometers (nm), where
unique phenomena enable novel applications not feasible
when working with bulk materials or even with single atoms
or molecules

8. Why
Nano-
therapeutics??
Better PK
Improved
dosing
requirements
Controlled
release of
drugsFaster
Biochemical
reaction
Better Side
Effect profile
Smaller &
Faster
devices

9. 1-100 nm
Man- made
Properties that arise as a result of nano-sized
dimension

12.  Fouling or opsonization of NPs by
proteins.
How to prevent fouling?
1. Neutral Antifouling coats
 Phosphatidylcholine groups,
sulfobetaines and carboxybetaine
2. Steric repulsion-Hydrophilic
polymer coats
PEG, polyoxazolines, HPMA,
polysaccharides, such as chitosan,
dextran, and hyaluronic acid

15. Membrane Wrapping
Endocytosis

16.  The concept here is to
envelop a targeted
nanoparticle with an
antifouling coating,
which will prevent
biological entities from
accessing the targeting
ligands
 Once the nanoparticle is
delivered to the tumoral
area, which then is
cleaved away, exposing
the ligands and allowing
for binding to the
intended cellular targets

17.  Drug delivery vehicles by Gregoriadis(1970)
 “Old drugs in new clothing”
 Aqueous inner space, or several of them,
which are surrounded by one or more
phospholipid bilayers
Diameters ranging 50-200
nm

18. Better efficacy & safety
Alters PK of a free drug by:
1. Enhanced permeability and retention effect (EPR effect)
2. Targeting of the mononuclear phagocytic system (MPS)
3. Multilamellar liposomes (MLVs) are the liposomes of
choice when using them as a slow or sustained release
drug carrier

19. Name Description Mechanism of action Approval/ Indication
AmBisome Amphotericin B
encapsulated in 60-
70 nm liposomes
Mononuclear
phagocytic system
targeting
FDA 1997
Systemic fungal infection
DaunoXo
me
Daunorubicin
citrate
encapsulated in 45
nm liposomes
Passive targeting FDA 1996
HIV- related Kaposi
sarcoma
DepoCyt Cytarabine
encapsulated in
multivesicular 20
μm liposomes
Sustained release:
cytotoxic conc. Of
drug in CSF for more
than 14 days after a
single 50 mg injection
FDA 2007
Lymphomatous
malignant meningitis
DepoDur Morphine sulphate
encapsulated in 17-
23 μm
multivesicular
liposomes
Sustained release FDA 2004
Treatment of chronic pain
in patients requiring long
term daily round-the-
clock opioid analgesic
(epidural space)26-02-2018 21

20. Name Description Mechanism of action Approval/ Indication
Doxil Doxorubicin
hydrochloride
encapsulated in 100 nm
Stealth liposomes
Passive targeting FDA 1995
AIDS related Kaposi sarcoma
Multiple myeloma
Ovarian cancer
Inflexal V Influenza virus antigens
on surface of 150 nm
liposomes
Liposomes mimic
native virus
structure
Switzerland 1997
Influenza vaccine
Marqibo Vincristine sulphate in
100 nm liposomes
Passive targeting FDA 2012
Acute lymphoid leukemia
Mepact Mifamurtide
incorporated into
multilamellar liposomes
Mononuclear
phagocytic system
targeting
Europe 2009
Non metastatizing resectable
osteocarcoma
Myocet Doxorubicin in 180 nm
liposomes
Mononuclear
phagocytic system
targeting
Europe 2000
Metastatic breast cancer
Visudyne Verteporfin in liposomes Drug solubilisation FDA 2000
Photodynamic therapy of age
related macular degeneration,
pathological myopia, ocular
histoplasmosis syndrome 22

21. FEATURES PREPARATION ROA
 Solid core – drug dissolved or dispersed in
solid high melting fat matrix
 Surfactant added for physical stabilization
(poloxamer 188, polyorbate 80, lecithin)
 High pressure
homogenization
 Microemulsion
formation
 Precipitation
 Parenteral
 Pulmonary
 Topical
 Oral
delivery of
lipid nano
pellets

22. Advantages
 Nontoxic compared to polymeric nanoparticles
 Cationic SLN can be effective, potent non viral transfection
agent
 Lipid components degrade slowly – provide long lasting
exposure to immune system

23. PEGylation of biologically active macromolecules generally
Increases their hydrodynamic radius
Prolongs their circulation and retention time
Decrease their proteolysis
Decreases their renal excretion
Shields antigenic determinants from immune
detection without obstructing the substrate-
interaction site

24. Name Description Approval/ Indication
Adagen Adenosine deaminase FDA 1990
Severe Combined Immunodeficiency
Syndrome
Cimzia Antibody (TNF-α) FDA 2008
Crohns disease
Rheumatoid arthritis
Neulasta Filgrastim FDA 2002
Febrile neutropenia
Oncaspar L- asparaginase FDA 1994
Acute lymphoblastic leukemia
Pegasys Interferon α-2b FDA 2002
Hepatitis B and C
PegIntron Interferon α-2b FDA 2002
Hepatitis C
Somavert Human growth hormone
receptor antagonist
FDA 2003
Acromegaly
Macugen Anti- VEGF FDA 2004
Intravitreal neovascular age related macular
degeneration
Mircera Erythropoeitin receptor
activator
FDA 2007
Anemia associated with chronic renal

25.  NPs with a core of silica & a coating of thin metallic shell
(gold)
 Can be guided to particular tissues such as cancer cells
 On exposure to infrared rays they are heated up to cause
selective tissue destruction

27.  Artificial macromolecules
 Tree like structures
 Atoms arranged in many branches
 Multivalent property
 Covalent attachment of special targeting moieties (sugar, folic
acid, antibody, biotin, EGFs) to achieve active targeting drugs
to tumor tissues

29.  Carbon allotrope Fullerenes are closed hollow cages consisting
of carbon atoms interconnected in pentagonal and hexagonal
rings.
 Bucky balls
 Light used to produce reactive oxygen from molecular
oxygen trigger apoptosis destroy most organic molecules
nearby (like tumors)
 Investigated for ability to "interrupt” allergy/immune
response
 Prevent mast cells from releasing histamine into blood & tissues
 Bind to free radicals better than other anti-oxidants

30.  Self-assembling sheet of atoms arranged in the form of tubes
and thread-like structures of nanoscale range
 Carbon based cage like structures – nanotubes and fullerenes
 Single walled and double walled
 Single walled more promising for drug and gene delivery
system

31. Modified gold nanoparticles (GNPs)
 Rod, multipod, star or a hollow structure such as shell,
box, cage
 Have promising applications in
 Fields of drug delivery
 Photothermal therapy in oncology
Due to their
 Unique optical & photothermal properties
 Ability to modify the surface & conjugate drugs/
molecules with gold nanomaterial

32.  Albumin has gained significant attention as a potential
carrier for therapeutic agents
 Albumin particles alter the PK of the free drug, subsequently
leading to its passive accumulation at the site of solid tumors
via the EPR effect
 Abraxane®, which comprises130 nm-sized nanoparticles
prepared from albumin with conjugated paclitaxel

33. Name Description Mechanism of action Approval/ Indication
Abraxane Nanoparticles (130
nm) formed by
albumin with
conjugated
paclitaxel
Passive targeting FDA 2005
Metastatic breast cancer,
non-small-cell lung cancer
Kadcyla Immunoconjugate.
Monoclonal
antibody (against
human epidermal
growth factor
receptor-2)
No mechanism
attributable to nano
size
FDA 2013
Metastatic breast cancer
Ontak Recombinant fusion
protein of fragment
A of diphtheria
toxin and subunit
binding to
interleukin-2
receptor
Fusionproteinbindsto
IL-2receptor,followed
byreceptor-mediated
endocytosis;fragmentA
ofdiphtheriatoxinthen
releasedintocytosol
whereitinhibitsprotein
synthesis
FDA 1994/2006
Primary cutaneous T-cell
lymphoma

34.  Composed of 100% water-insoluble drug without any added
excipient or any associated nanocarrier system
 Increase in saturation solubility it increases with decreasing
particle size below 1000 nm
 Noyes and Whitney equation(1897)
Increase of dissolution velocity by
surface area enlargement
 Drug nanocrystals possess increased Saturation solubility,
which in turn increases the concentration Gradient between
gut lumen and blood, and thereby increases the absorption by
passive diffusion

35. Name Description Mechanism
of action
Approval/ Indication
Emend Aprepitant
Increased
dissolution
rate
FDA 2003
Emesis, antiemetic
(oral)
Megace
ES
Megestrol acetate FDA 2005
Anorexia, cachexia
(oral)
Rapamune Rapamycin
(sirolimus)
FDA 2002
Immunosuppressant
(oral)
Tricor Fenofibrate FDA 2004
Hypercholesterolemia,
hypertriglyceridemia
(oral)
Triglide Fenofibrate
FDA 2005 37

37. Name Description Mechanism of
action
Approval/
Indication
Fungizone Lyophilized powder
of amphotericin B
with added sodium
deoxycholate.
Forms upon
reconstitution
colloidal (micellar)
dispersion
Drug solubilization:
Rendering drug
biocompatible and
enhancing ease
of administration
after Iv injection
FDA 1966
Systemic fungal
infections (Iv)
Diprivan Oil in water
emulsion of
propofol
Drug
solubilisation
FDA 1989
Induction and
maintenance of
anesthesia
Estrasorb Emulsion of
estradiol in
soyabean oil
Drug
solubilisation
FDA 2003
Hormone
replacement
therapy

38. Name Description Mechanism of action Approval/ Indication
Copaxone Glatiramer Based on its resemblance
to myelin basic protein,
glatiramer is thought to
divert as a “decoy” an
autoimmune response
against myelin
FDA 2014
Multiple sclerosis (SC)
Eligard Leuprolide acetate
incorporated in NP
composed of PLGH
copolymer
Sustained release FDA 2002
Advanced prostate cancer (SC)
Genexol Paclitaxel Passive targeting South Korea 2001
Metastatic breast cancer,
pancreatic cancer (Iv)
Opaxio Paclitaxel Passive targeting FDA 2012
Glioblastoma
Renagel Cross-linked poly
allylamine
hydrochloride
Phosphate binding FDA 2000
Hyperphosphatemia (oral)
Zinostatin
stimalame
r
Conjugate protein
or copolymer of
styrenemaleic acid
and an antitumor
Passive targeting Japan 1994 Primary
unresectable
hepatocellular carcinoma

39. Name Description Mechanism of action Approval/ Indication
Feridex Superparamagnetic
iron oxide
nanoparticles
coated with dextran
MPS targeting: 80%
taken up by liver and
up to 10% by spleen
within minutes of
administration. Tumor
tissues do not take up
these particles and
thus retain their native
signal intensity
FDA 1996
Liver/spleen lesion MRI
Feraheme Superparamagnetic
iron oxide
nanoparticles
coated with
dextran.
MPS targeting FDA 2009
Treatment of iron
deficiency anemia in
adults with chronic
kidney disease
NanoTher
m
Aminosilane-coated
superparamagnetic
iron oxide 15 nm
nanoparticles
Thermal ablation Europe 2013
Local ablation in
glioblastoma, prostate,
and pancreatic cancer

52.  Nanotechnology offers potential developments in
pharmaceuticals, medical imaging and diagnosis, cancer
treatment, implantable materials, tissue regeneration, and
even multifunctional platforms combining several of these
modes of action into packages a fraction the size of a cell