Targeted drug delivery system

TDDS ( Current & Recent approaches )

1. TARGETEDDRUGDELIVERYSYSTEM
Presented by : Ms. TabassumKhajuShaikh
F.Y M.Pharmacy[ Pharmaceutics ] Sem-1
Guided By : Mr. DevendraVisokarSir

2. CONTENT’S
▪Introduction
▪Need of Targeted drug delivery system
▪Type’s of Targeted drug delivery
▪Drug delivery vehicle
▪Various Targeting site’s
▪Research works on TDDS
▪TDDS vehicles in Covid-19 patient’s
▪Conclusion
▪Reference

3. INTRODUCTION
•‘Targeted drug delivery system is a special form of drug
delivery system where the medicament is selectively
targeted or delivered only to its site of action or
absorption’.
•Targeted drug delivery system is preferred over conventional
drug delivery systems due to three main reason’s.
i.Pharmaceutical properties –TDDS have Higher solubility &
drug stability
ii.Pharmacokinetic properties –TDDS posses high
Absorption, Good half life & Low volume of distribution.
iii.Pharmacodynamicproperties –TDDS have High specificity
and High therapeutic index.

4. ❑Characteristics of Targeted drug delivery system
•Should be biochemically inert.
•Should be non immunogenic.
•Should have therapeutic amount of drug release.
•Carriers used should be biodegradable.
•Should be physically and chemically stable in vivo and in vitro
conditions.
❑Application of Targeted drug delivery system
•Targeted drug delivery can be used to treat many diseases, such as
cardiovascular diseases and diabetes. Most importantly in cancerous
tumors.
•Liposomes can be used as drug delivery for the treatment of
tuberculosis.

5. ❑Generation of drug delivery system
•There are five generations of drug delivery system.
Generation of drug delivery
First
Generation
DDS:
Tablet,
Capsule
Ointment
Suspension
Emulsion
Suppositories.
Second
Generation
DDS:
Repeat action
Tablet,
Prolong action
Tablet,
Enteric coated
Tablet.
Third
Generation DDS:
Osmotically
controlled system,
Swelling
controlled system,
Diffusion
controlled system
Fourth
Generation DDS:
Targeted drug
delivery system
Modulated drug
delivery system
Self regulated
Drug delivery
system
Fifth
Generation
DDS:
Gene therapy
under various
phase of
development

6. NEEDOFTARGETEDDRUGDELIVERYSYSTEM
•The need of this system is to deliver the certain amount of drug
to the targeted diseased area within the body. This will help to
maintain the required plasma level and tissue drug level in the
body therefore avoiding any damage to the healthy tissue via
drug.
Need of Targeted Drug Delivery
System
Pharmacokinetic
Reasons
Pharmacodynamic
Reasons
Pharmaceutical
Reasons
Low
Solubility
Drug
Instability

7. ❑Advantages of TDDS
•TDDS reduces the side effects and toxicity.
•Dose of the drug reduces.
•It avoids the degradation of drug (first pass metabolism).
•Drug bioavailability increases and fluctuation in concentration
decreases.
❑Disadvantages of TDDS
•Advanced techniques and skilled persons are required.
•Sometimes it may causes toxicity and it is very difficult to
maintain stability of dosage forms.

8. TYPESOFTARGETEDDRUGDELIVERYSYSTEM
▪Active targeting -Employs a deliberately modified drug carrier
molecule capable of recognizing and interacting with specific
cell tissue or organ in the body e.g., antigen specific antibody.
▪Passive targeting -Drug delivery systems which are targeted to
systemic circulation are characterized as Passive delivery
systems.
Level’s of Drug targeting
First order
targeting
Third order
targeting
Second order
targeting

9. There are different approaches to actively target drugs to the
site of action like ligands, immune reaction, external stimuli
etc.

10. •Ligand mediated targeting –Achieved using specific
mechanisms such as receptor dependent uptake of natural LDL
particles and synthetic lipid microemulsionsof partially re
constituted LDL particles coated with the apoproteins.
Ligands Target Tumortarget
Folate Folatereceptor Overexpression of
folate
receptor
Transferrin Transferrin receptorOverexpression of
transferrin
receptor
Galactosamine Galactosamine
receptors
on hepatocytes
Hepatoma

11. ▪Inverse targeting -This approach leads to saturation of RES and
suppression of defensemechanism. This type of targeting is a effective
approach to target drug to non-RES organs.
▪Dual targeting -In this targeting approach carrier molecule itself have
therapeutic activity and thus increase the therapeutic effect of drug. Ex,
Anti-viral Drug
▪Double targeting –Targeting drug at specific site & Controlling the
rate of drug delivery to the target site, these both activity combined to
to target a carrier system, then targeting may be called double
targeting.
▪Combination targeting -These targeting system is equipped with
cariers, polymers and homing devices of molecular specificity that
could provide a direct approach to target site.

12. DRUGDELIVERYVEHICLE
•Most important for successful transportation of the loaded
drug at the specific site.
❑Characteristics of an ideal drug Vehicle
•Should be able to cross Blood Brain Barrier.
•It must be recognized by target cell’s.
•After recognition, system should release the drug inside the
target organs, tissues or cells.
•Non-toxic
•Non-immunogenic
•Biodegradable

13. ❑Vehicles for targeting drugs :
▪Liposomes -Liposomes are small artificially designed vesicles
composed of phospholipid bilayers surrounding with the size
ranging from 20 to 10 000 nm. Encapsulation of drug used for
both active & passive targeting. These are extensively
researched for their application in non-viral vector mediated
gene therapy.
▪Monoclonal antibodies and fragments -MABs are highly
specific and recognize only are antigenic determinant or
receptor site. MABs coupled with an active drug hold great
promises for site specific delivery of biological substances,
particularly in cancer chemotherapy.

14. .
▪Modified plasma proteins –Intelligent drug vehicle, Bczof
there solubility & low Molecular weight, Easily get modified
with attachments of different molecules( sugar, peptides,
ligands ) . Extensive modification are used in liver cell
targeting.
▪Quantum dots -Quantum dots are miniscule semiconductor
particles that can serve as sign posts of certain types of cells
or molecules in the body. Technique has potential for
targeting cancerous drug.

15. ▪Microspheres and nanotechnology –Microspheres are,
Microcapsulationin which solid is envolopedin membrane that
may be impermiableor semi-permiable. With particle size
200μm, important approach in delivering drug with sustain &
controlled manner EX, Narcotic, Antagonist, Steroid hormones.
▪Lipoproteins –LDL & HDL are natural targeted liposomes, it’s
core used to incorporate lipophilic drugs and it does not require
covalent bonding with the drug. Used for drug targeting liver.

16. ADVANCEDCARRIERSFORTARGETINGDRUGS
▪NanoTubes-They are hollow cylinder made of carbon,
atoms which can be filled and sealed for potential drug
delivery.
Cellular scale needle for attaching drug molecule to cancer
cells. As an electrode in thermo cells.
▪Nano wires -the nanowire pinpoint damage from injury and
stroke, localize the cause of seizures,

17. and detect the presence of tumorsand other brain
abnormalities.
Technique has potential as a treatment for Parkinson's and similar
diseases.
▪Nanoshells-Nanoshellsare hollow silica spheres covered with
gold. Scientists can attach antibodies to their surfaces, enabling
the shells to target certain shells such as cancer cells.

18. Technique has potential for targeting cancerous drug.
Nano pores -Engineered into particles, they are holes that are
so tiny that DNA molecules can pass through them one strand at
a time, allowing for highly precise and efficient DNA sequencing.
Potential in genetic engineering and bio technology.

19. ▪Gold Nano Particle -Scientist uses gold nanoparticle to
develop ultrasensitive detection system for DNA and protein
markers associated with many forms of cancer, including breast
prostrate cancer.
In cancer Treatment and Genetic engineering.
▪Dendrimers-Dendrimersprecisely defined, synthetic
nanoparticles that are approximately 510 nm in diameter. They are
made up of layers of polymer surrounding a control core. The
dendrimerssurface contains many different sites to which drugs
may be attach.

20. In gene transfection, medical imaging.

21. VARIOUSTARGETINGSITES
▪Targeting GIT :
•Various site-specific oral controlled release systems have
been developed depending upon the target site which can be
classified as:
I. Systems targeted at stomach / duodenum
II. Systems targeted at small intestine
III. Systems targeted at lymphatic
IV. Systems targeted at colon
▪Systems targeted at stomach \duodenum:
•Prolongs stomach residence time, Active ingredients reach at
optimum absorption site, Generally includes drugs ( insoluble
in GIT fluid, Drugs having site-specific action on
stomach\deodenum,Highlyacidic drugs ).

22. ▪Systems targeted at small intestine:
•Used to permit safe passage of system through acidic
environment of the stomach. Generally includes ( drugs
destroyed by gastric acid, drugs irritating to gastric mucosa &
with site specific action ).
▪Systems targeted at lymphatic:
•Lymphatic system consists of a network of vessels through
the small and large intestines which are involved in the
potential uptake of particulate administered drug in
micrometerrange. Generally used for ( To avoid first pass
metabolism, mesenteric lymphatic treatment, Inhibition of
cancer cell metastasis, highly hydrophobic drugs )

23. ▪Systems targeted at colon:
•The delivery of drugs to the colon for local effect is valuable
in a variety of conditions like inflammatory bowel diseases
(e.g., Ulcerative colitis and Crohn’sdisease), infectious
diseases and colon cancer. Have a higher residence time so
increase the absorption of poorly absorbing drug material.
•Mainly this system is used for,
i.Drugs with site-specific action in colon
ii.For macromolecules like proteins & peptides
iii.Poorly absorbing drugs
iv.To avoid first pass metabolism

24. ▪Targeting the respiratory tract :
•Generally Bronchodilator & Anti-inflammtorysteroids used
for effective control on asthma.
•Used for local & systemic effect & also for,..
i.Avoiding first pass effect.
ii.Rapid onset of action.
iii.Better patient compliance.
iv.To enhance bioavailability.
v.For protein & peptide
drug moieties.

25. ▪Targeting the brain :
•The blood brain barrier (BBB) is a unique protective barrier that
provides a very efficient exclusion of variety of blood
components by obstructing free flow of blood between brain &
rest of body. Also restricts the penetration of hydrophilic drugs,
unless these are transported to the brain by an active transport
system.
•Ex, dopamine was delivered using the N1-substituted
dihydropyridinepyridiniumsalt type redox system.

26. RESEARCHWORKSONTARGETEDDRUGDELIVERYSYSTEM
S.N
o
Active
ingredient
Other
ingredient
Method
employed
Effect
1 Meloxicam Ethyl celluloseTablet
Compre-
ssion
and coating
Retarded the drug
release upto12hrs and
shows
max. of 98.69% drug
release
2 ParacetamolDextrin,
Polysaccha
ride
Wet
granulation
Tablet containing dextrin
as a carrier and ethyl
cellulose as a binder
found to be suitable for
targeting paracetamolfor
local action in the
colon Matrix tablets
containing dextrin
released
95-98% paracetamol.

27. .
S.
No
Active
ingredient
Other
ingredient
Method
employed
Effect
3Doxorubicn
hydrochloride
ChitosanHPLC In-vitro release of
doxorubicin is of zero
order kinetic. This shows
that release is independent
of the concentration of
drug loaded in the
nanospheres.
4DiltiazenHCL
and
indomethacin
Polysaccha
ride,
inulin and
shellac
Tablet
compression
and coating
Studies revealed that the
tablet coated with
inulin and shellac have
limited the drug release
in stomach and small
intestine. And released
maximum amount of drug
in in colonic
environment.

28. TARGETEDDELIVERYVEHICLESOFTHERAPEUTICS
COVID-19 PATIENT’S
•All treatments rely on systemic delivery but COVID-19 damages
the lungs preferentially.
•So use of a targeted delivery approach is reviewed where
engineered products are able to reach damaged lung tissue
directly.
•Only 2 pharmaceuticals have demonstrated signals toward
efficacy, Remdesivir& Dexamethasone.
•Targeted drug delivery of these promising pharmaceuticals
might prove to be more effective, enhancing the local effect.
•SARS-CoV-2 has an affinity for 2 host cell factors, ACE-2 and
TMPRSS2.

29. SOMEOFTHENEWERAPPROACHESFORTARGETEDDRUG
DELIVERYINCOVID-19 PATIENTS
▪Microbubbles-Microbubblesspecifically have shown to adhere
to sites of damaged vascular endothelium and thus may be a
method of systemically targeting delivery of therapeutics to
damaged lungs with SARS-CoV-2.
▪Extracellular Vesicles (EV)-EVs play a critical role in cell-to-
cell communications and can be used as unique drug carriers to
deliver protease inhibitors to treat COVID-19.

30. Covid-19 & Extracellular Vesicles (EV)
(Isolation and drug encapsulation techniques employed to engineer EVs
could result in the loss of functional properties of the Evs.)

31. ▪Adenosine Nanoparticles -The efficacy in mitigating
inflammation was demonstrated through the targeted delivery of
adenosine and of multidrug formulations. This nanoparticle
improves the bioavailability of both drugs with significant
pharmaceutical activity, so several clinical studies planned to use
this technology in patients with COVID-19.
▪Direct Pulmonary Delivery -Direct pulmonary delivery (e.g.,
aerosol, inhalers, etc.) is a more selective mode of drug delivery.
Currently, 2 studies are enrolling -the NOSARSCOVID Phase II
Trial and the Pulsed Inhaled Nitric Oxide for Treatment of
Patients with Mild or Moderate COVID-19.
▪Catheter-Based Drug Delivery -Catheter-based local drug
delivery of antivirals (liquid remdesivir) and/or pro-
inflammatory cytokine inhibitors (tocilizumab) can be
performed trans-pulmonary, with a Swan-Ganzcatheter.

32. CONCLUSION
•Delivery of drug molecule to reach its specific site is itself a
difficult task. Finally, a targeted drug delivery is coming towards
as an advanced technique used in the treatment of lethal
diseases.
•The advantage of this technique has been the reduction in dose
and side effects of the drug.
•Overall it may be concluded as wiser technique.

33. REFERENCE
▪AmanKumar1*, UjjwalNautiyal1, CharanjeetKaur, Vaishali
Goel1,Neha Piarchand.Targeted Drug Delivery System: Current and
Novel Approach, (Review article)
▪Mrs Jaya Agnihotri*1, Dr.ShubhiniSaraf2, Dr.AnubhaKhale
.11,3M.E.S. Instititute’s, TARGETING : NEW POTENTIAL CARRIERS
FOR TARGETTED DRUG DELIVERY SYSTEM( Review article)
▪Gupta Manish and Sharma Vimukta. Targeted drug delivery system:
(A Review )
▪: H. S. Mahajan, S. B. Patil*, S. G. Gattani*, B. S. Kuchekar**Targeted
drug delivery systems
▪,KirtiRani*, SaurabhPaliwalA Review on Targeted Drug Delivery:
its Entire Focus on Advanced Therapeutics and Diagnostics.

34. ▪Nicholas Kipshidze, Patrick Iversen, Thomas R. Porter, Nodar
Kipshidze, FakihaSiddiqui, George Dangas, and Jawed Fareed,
Targeted, Site-Specific, Delivery Vehicles of Therapeutics for
COVID-19 Patients.
•Banker GS, Rhodes CT. In: Modern Pharmaceutics, 3rd ed.
MarcelDeckerInc: New York;1996.

35. THANKYOU