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New Drug Delivery
System
Dr Karuna Sree P
Asst. Professor
Dept. Of Pharmacology
KIMS
Contents
–Introduction
–Disadvantages of current routes of
administration
–Novel drug delivery system
–Types : controlled & Target DDS
• Mechanism of CDDS
• Drug carriers in target DDS
–Conclusion
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
3/23/2015
Dr Karuna Sree, Dept. Of
Pharmacology, KIMS
Introduction…
• The method by which a drug is delivered can have
a significant effect on its efficacy.
• Some drugs have an optimum concentration range
within which maximum benefit is derived
(Therapeutic Index) and concentrations above or
below this range can be toxic or produce no
therapeutic benefit at all.
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Introduction…
Pharmaceuticals : Primarily
consists of drugs given either
Orally (as solid pills and liquids)
or injectables or as topical / local
applications.
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Routes
of Administration
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Disadvantages in current therapy
• Inactivation by gastric juice
• Metabolism before reaching target cell – First pass
metabolism in lung / liver / Intestine
• Too many adverse reactions
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
How to overcome this???
• By improving rate of drug delivery
• Decreasing Biodegradation
• Time release medications
• Site-specific targeting
• Finding ways to administer injectable only
medications in oral form
• Costly, multiple-dose, long-term therapies →
Inexpensive, potent, time-releasing or self-
triggering formulations.
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
How to overcome this???
To combat this a multidisciplinary approach that
combine Pharmaceutics, Polymer Science, Bio-
conjugate Chemistry, and Molecular Biology in
controlling the Pharmacokinetics,
Pharmacodynamics, Non-specific Toxicity,
Immunogenicity, Bio recognition and efficacy of
drugs were generated which is called novel drug
delivery systems (DDS).
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Novel Drug Delivery System
Aims to deliver the drug at a rate
directed by the needs of the body
during the period of treatment, and
target the active entity to the site of
action
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Novel Drug Delivery System cont…
–Controlled drug delivery system
–Target drug delivery system
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
CDDS : Mechanism of
drug delivery Drug delivery
activation
Physical
Osmotic
pressure
Hydrodynamic
pressure
Vapour pressure
Mechanically
Magnetically
Sonophoresis
Iontophoresis
Hydration
Chemical
pH activated
Ion activated
Hydrolysis
Biochemical
Enzyme
Feed back
regulated:
Bioerosion
Bio-responsive
Self regulatory
Energy
supplied
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
CDDS
• Some of the examples for CDDS
– Oral CDDS
– Nasal CDDS
– Drug eluting stents
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
CDDS cont…
Advantages of CDDS :
• Patient compliance is improved due to decreased
frequency in dosing
• Reduced severity and toxicity of side effects.
• More constant blood level improves therapeutic action.
Disadvantages of CDDS :
• Cost
• Uncontrolled poisoning if poor formulation result in fast
and high drug release.
• Not suitable for many drugs that are absorbed from
particular region.
• Irritation at site of application.
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Oral CDDS
• Modified Release DDS
• Extended Release DDS
• Delayed Release DDS
• Repeated Action DDS
• Prodrug
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Modified Release DDS : drug is released based
on time course and/or location for therapeutic or
convenience. Eg. Enteric coated-diclofenac EC
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Delayed Release DDS : one or more immediate
release unit → single DF. The delay may be
time-base or based on influence of
environmental conditions as GIT pH.
Oral CDDS
• Extended Release DDS : ↓ dosing frequency. Eg.
Diclofenac SR, nifedipine SR
• Repeated Action DDS : Layer tablet – 2 or 3
compressed together: sustained release +
immediate release unit.
• Prodrug
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Prodrug
• Prodrug is an inactive form of drug
which gets metabolized in the body to
an active drug
• Used to overcome the
pharmacokinetic disadvantage of
useful drug E.g. : levodopa
• To provide longer duration of action.
e.g. – Procaine Penicillin, Benzathine
pencillin
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Nasal drug delivery
• As aerosols, metered dose inhalers, dry powder
inhalers(rotahalers) and Nebuliser
– E.g .: Anti histaminic - Astemizole
– Desmopressin in Rx of Diabetes insipidus
– Calcitonin
– Insulin can be given as inhalers instead of SC
inj. Which have better patient compliance
(approved in june 2014 by FDA)
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Drug Eluting stents
• A metallic stent contains
drug which is gradually
released over 14-30 days
• Drugs used are :
Sirolimus, Paclitaxel,
everolimus
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Computerized Miniature Pumps
• These are programmed
to release drugs at a
definite rate either
continuously or
intermittently in pulses.
–Insulin pump
–GnRH pump
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Site Specific / Targeted DDS
• Specific medium / carrier is required that can
control the therapy’s administration by means of
either a physiological or chemical trigger
• To achieve this vast research going in micro &
nano technology.
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Drug carriers
• Polymeric microspheres
• Polymer micelles
• Biodegradable polymers (natural-cellulose or
synthetic-polyanhydrides/polyesters/polyacrylic
acids/polyurethane)
• Dendrimers (star polymers)
• Electro-active polymers
• Magnetic microcarriers
• Modified C-60 fullerenes (bucky balls)
• Hydrogel-type materials
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Some Drug carriers…
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Types of polymers
• Polymer Microspheres : Two types
– Reservoir type (drug is encapsulated-chocolate
wrapper)
– Matrix like (drug physically entrapped in a
polymer network-cookie with chocolate crunch in
between)
• Polymers micelle may be single or polymeric
micelle (hydrophobic and hydrophilic)
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Polymer microspheres
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Targeted drug delivery cont…
Examples
• Ocusert
• Progestasert
• Transdermal drug delivery / subcutaneuous
delivery
• Liposomes
• Monoclonal antibodies
• Erythrosomes
• Dendrimers
• Nanotechnology- nanosomes, nanorobots
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Ocusert
• Thin elliptical micro units
containing drug in reservoir
• Eg : Pilocarpine ocusert used
in Glaucoma placed
– Site : Under lower eyelid
delivers the drug for a
period of 7 days
– Adv. – Pilocarpine is a
short acting drug given 6th
hrly is avoided.
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
3/23/2015
Dr Karuna Sree, Dept. Of
Pharmacology, KIMS
Retisert –
Fluocinolone
acetonide – Rx non
–infectious uveitis
Gancyclovir –
Rx of CMV
retinitis
Latanoprost
Progestasert
• Drug is entrapped in solid polymer i.e., silicon
rubber and implanted or injected in to the body.
• Progestasert : It is an IUCD inserted into uterus
delivers progesterone at a constantly specified rate
for 1yr.
• ADV. : No missing of dose
• DISADV. : Ectopic pregnancy
– Chances of PID
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Transdermal Adhesive Patch
• Drug is incorporated into a
polymer reservoir
• Provides steady & smooth
plasma conc. for a period of 1-
7 days
• Site of application : Chest,
Abdomen, Upper Arm, lower
Back, Buttock Or Mastoid
Region
• Size : 5-20 cms and available
in various shapes.
• E.g. : Nitroglycerin, Nicotine,
Estradiol, Hyoscine, Fentanyl
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Transdermal Adhesive Patch cont…
• Adv. – more convenient and
better patient compliance
• ADR : Local Irritation,
Erythema
• Disadvantage : Drug
delivery is slow & passive,
large molecular wt drugs
cannot be delivered, lack of
dosage flexibility.
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Transdermal Drug
delivery…
• Iontophoresis : Galvanic
current allows the penetration
of drug applied to the skin into
deeper tissues.
– Anode iontophoresis -
compounds with positive
charge
– Cathode iontophoresis –
compounds with negative
charge.
– E.g. Salicylates
• Laser-assisted Transdermal
drug delivery
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Special delivery forms in
Subcutaneous route
• Dermojet : Needle is not used.
– A high velocity jet of drug
solution injected using gun
like implement and Solution
gets deposited in
subcutaneous tissue.
– Essentially painless and
suited for mass inoculations.
– Eg. Insulin
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Special delivery forms in SC route
• Pellet implantation : Drug in solid pellet form
introduced with a trochar and canula.
– Provides sustained release of drug over weeks
and months. Eg. DOCA, Testosterone
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Special delivery forms in
SC route cont…
• Sialistic (Non biodegradable)
and Biodegradable implants :
Crystalline drug is packed in
tubes or capsules made of
suitable materials and
implanted under skin.
• NORPLANT - Levonorgestrel
subdermally implanted
provides
contraception for a period of 5
yrs.
ADV. : No missing of dose
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Liposomes as Drug carriers
• These are minute vesicles and consists one or
more phospholipids bilayers.
• May be unilamellar, multilamellar or multivesicular
• Filled with non lipid soluble drugs and retained until
liposome is disrupted.
• Niosomes : similar to Liposomes but has non-ionic
surfactants instead of phospholipids in the bilayer
formation
• Eg : Amphotericin, Daunorubicin, Doxorubicin,
Azithromycin, Vincristine(approved in 2012)
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Advantages of Liposomes in DDS:
• Increased stability and decreased toxicity
of encapsulated drug.
• Better pharmacokinetic, good therapeutic
index.
• Both hydrophilic and hydrophobic drugs
can be carried.
• Biologically inert, biodegradable, non-
toxic, non-antigenic, non- pyrogenic.
• Disadvantage: Highly expensive
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Monoclonal antibodies
• These are Antibodies produced by a single clone
and are directed against a single antigenic
determinant (epitope)
• Mabs are produced on large scale using
Hybridoma technique.
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Mouse inj. With Ag
having epitopes
a & b
Expansion &
elusion of MAb
It produces
B-lymphocytes
to each epitope
B1 B2
a b
B1-My
a
B1-My
a
a a a
a a
The desired
activated Bi fused
with Myeloma cell
in Polyethylene
glycol
Growth of hybridoma in HAT medium & cloning
MAbs cont…
• Murine MAbs not preferred now a days due to
shorter half life and ability to induce allergic
reactions
• Chimeric MAbs : partly human and partly mouse
antibody
• Humanised MAbs –least Antigenic
• In the name of Mabs the letter before mab
indicates source of antibody i.e., “O” for murine
(Muromonab)
– “Xi” – chimeric (Rituximab, Abciximab)
– “Zu” - human (Omalizumab, Pavlizumab)
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Dendrimers
• Dendritic macromolecules (highly branched,
globular) :
• Used to encapsulate individual small drug
molecules (unimolecular nanocapsule)
• Can also serve as “hubs” onto which large
numbers of drug molecules can be attached via
covalent bonds.
• Eg. : Anticancer agents 5-fluorouracil to
polyaminoamine dendrimers
• Methotrexate to hydrazide-terminated dendrimers
formed from poly aryl ether.3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Dendrimer…
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Bacterial ghosts/Artificial cells as carriers
• Different species of microorganisms have been
used to produce ghosts like Salmonella,
Pasteurella hemolytica, Actinobacillus
pleuropneumoniae, E.coli
• Artificial Cells : Size & structure same as biological
cell with some functional property of biological
cells.
• E.g. Microencapsulation of islets of pancreas,
hepatocytes, cholesterol removing3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Bacterial Ghost
Hydrogel carriers
• Hydrogels are hydrophilic, polymeric networks
capable of imbibing large amounts of water or
biological fluids.
• Hydrogels are stimuli-sensitive gel systems
modulate release in response to pH, temperature,
ionic strength, electric field, or specific analyte
concentration differences.
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Micro Electro Mechanical System
(MEMS)
• Dorian Liepmann and Boris Stoeber developed MEMS
syringe, the size of a fingernail.
• It is pre-loaded with a lyophilized, or freeze-dried, drug
stored in its silicone rubber reservoir.
• The "shot/drug" is delivered by pressing the device
against the skin for a few seconds.
• The dry drug is pushed through the microneedles into
the skin where the body's interstitial fluids assist in
rapidly absorbing the drug directly into the
bloodstream.
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
MEMS
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Nano particles
• Nanoparticles includes Nanospheres and
Nanocapsules of size 10-200 nm which are solid
particles, either amorphous or crystalline formed
from biodegradable or non biodegradable
polymers.
• Nanocapsules : These are vesicular systems in
which the drug is confined to a cavity surrounded
by a unique polymer membrane
• Nanospheres : These are matrix systems in which
the drug is physically and uniformly dispersed.3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Nanoparticles as carriers
• Nanoparticles have many applications, including
anti-tumour therapy, gene therapy, AIDS therapy,
radiotherapy, in the delivery of proteins, antibiotics,
virostatics, vaccines and as vesicles to pass the
blood-brain barrier.
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Nano - Erythrosomes as carriers
• Drug loaded in body’s own
erythrocytes.
• Also called GOLDEN EGGS.
ADVANTAGES:
• Biocompatible
• Nontoxic with minimum ADR.
• Non-nucleated so large space
available for drug
incorporation.
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Nano - Erythrosomes as carriers
• Eg. : Insulin, L-asparginase, Heparin
• Antiviral Agents: Acyclovir.
• Cancer Chemotherapy drugs : Methotrexate,
Bleomycin, Adriamycin.
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Nanotechnology in healthcare…
• Nanotechnology offers tools
and techniques for more
effective detection, diagnosis
and Rx of diseases
• Lab on chips help detection &
diagnosis of diseases more
efficiently
• Nanowire help in early
detection of cancer biomarkers
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Nanotechnology in Cancer
• The mixture of two
different-sized
nanoparticles work with the
body's bloodstream to seek
out, stick to and kill
tumors.
• One is designed to find the
cancerous tumor and
then adhere to it, while
the
second is designed to
then kill the tumor cells.3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Nano-Robots
• Nano-Robots in treatment of cancer.
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Magnetic Micro carriers
• Include Magnetic Microspheres, Magnetic
Liposomes, Magnetic Nanoparticles, Magnetic
Resealed Erythrocytes, Magnetic Emulsion etc.
• Magnetic Micro/Nanoparticle & molecular magnetic
labels have been used for great number of
application in various areas of biosciences,
targeted drug delivery, imaging & in bio separation
technology.
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Future Challenges in nanotechnology
– The main goals are to improve their stability in
the biological environment
– To mediate the bio-distribution of active
compounds
– The cytotoxicity of nanoparticles or their
degradation products remains a major problem
– Improvements in biocompatibility
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
Conclusion
• NDDS – is for controlled & targeted delivery of
drug for better absorption, site specific action with
minimal adverse reactions.
• Future of drug delivery influenced by micro
fabrication / nanotechnology.
• The question is how best to achieve this goal.
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,
3/23/2015
Dr Karuna Sree, Dept. Of Pharmacology,

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New drug delivery systems

  • 1. New Drug Delivery System Dr Karuna Sree P Asst. Professor Dept. Of Pharmacology KIMS
  • 2. Contents –Introduction –Disadvantages of current routes of administration –Novel drug delivery system –Types : controlled & Target DDS • Mechanism of CDDS • Drug carriers in target DDS –Conclusion 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 3. 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology, KIMS
  • 4. Introduction… • The method by which a drug is delivered can have a significant effect on its efficacy. • Some drugs have an optimum concentration range within which maximum benefit is derived (Therapeutic Index) and concentrations above or below this range can be toxic or produce no therapeutic benefit at all. 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 5. Introduction… Pharmaceuticals : Primarily consists of drugs given either Orally (as solid pills and liquids) or injectables or as topical / local applications. 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 6. Routes of Administration 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 7. Disadvantages in current therapy • Inactivation by gastric juice • Metabolism before reaching target cell – First pass metabolism in lung / liver / Intestine • Too many adverse reactions 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 8. How to overcome this??? • By improving rate of drug delivery • Decreasing Biodegradation • Time release medications • Site-specific targeting • Finding ways to administer injectable only medications in oral form • Costly, multiple-dose, long-term therapies → Inexpensive, potent, time-releasing or self- triggering formulations. 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 9. How to overcome this??? To combat this a multidisciplinary approach that combine Pharmaceutics, Polymer Science, Bio- conjugate Chemistry, and Molecular Biology in controlling the Pharmacokinetics, Pharmacodynamics, Non-specific Toxicity, Immunogenicity, Bio recognition and efficacy of drugs were generated which is called novel drug delivery systems (DDS). 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 10. Novel Drug Delivery System Aims to deliver the drug at a rate directed by the needs of the body during the period of treatment, and target the active entity to the site of action 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 11. Novel Drug Delivery System cont… –Controlled drug delivery system –Target drug delivery system 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 12. CDDS : Mechanism of drug delivery Drug delivery activation Physical Osmotic pressure Hydrodynamic pressure Vapour pressure Mechanically Magnetically Sonophoresis Iontophoresis Hydration Chemical pH activated Ion activated Hydrolysis Biochemical Enzyme Feed back regulated: Bioerosion Bio-responsive Self regulatory Energy supplied 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 13. CDDS • Some of the examples for CDDS – Oral CDDS – Nasal CDDS – Drug eluting stents 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 14. CDDS cont… Advantages of CDDS : • Patient compliance is improved due to decreased frequency in dosing • Reduced severity and toxicity of side effects. • More constant blood level improves therapeutic action. Disadvantages of CDDS : • Cost • Uncontrolled poisoning if poor formulation result in fast and high drug release. • Not suitable for many drugs that are absorbed from particular region. • Irritation at site of application. 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 15. Oral CDDS • Modified Release DDS • Extended Release DDS • Delayed Release DDS • Repeated Action DDS • Prodrug 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 16. 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology, Modified Release DDS : drug is released based on time course and/or location for therapeutic or convenience. Eg. Enteric coated-diclofenac EC
  • 17. 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology, Delayed Release DDS : one or more immediate release unit → single DF. The delay may be time-base or based on influence of environmental conditions as GIT pH.
  • 18. Oral CDDS • Extended Release DDS : ↓ dosing frequency. Eg. Diclofenac SR, nifedipine SR • Repeated Action DDS : Layer tablet – 2 or 3 compressed together: sustained release + immediate release unit. • Prodrug 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 19. Prodrug • Prodrug is an inactive form of drug which gets metabolized in the body to an active drug • Used to overcome the pharmacokinetic disadvantage of useful drug E.g. : levodopa • To provide longer duration of action. e.g. – Procaine Penicillin, Benzathine pencillin 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 20. Nasal drug delivery • As aerosols, metered dose inhalers, dry powder inhalers(rotahalers) and Nebuliser – E.g .: Anti histaminic - Astemizole – Desmopressin in Rx of Diabetes insipidus – Calcitonin – Insulin can be given as inhalers instead of SC inj. Which have better patient compliance (approved in june 2014 by FDA) 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 21. Drug Eluting stents • A metallic stent contains drug which is gradually released over 14-30 days • Drugs used are : Sirolimus, Paclitaxel, everolimus 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 22. Computerized Miniature Pumps • These are programmed to release drugs at a definite rate either continuously or intermittently in pulses. –Insulin pump –GnRH pump 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 23. Site Specific / Targeted DDS • Specific medium / carrier is required that can control the therapy’s administration by means of either a physiological or chemical trigger • To achieve this vast research going in micro & nano technology. 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 24. Drug carriers • Polymeric microspheres • Polymer micelles • Biodegradable polymers (natural-cellulose or synthetic-polyanhydrides/polyesters/polyacrylic acids/polyurethane) • Dendrimers (star polymers) • Electro-active polymers • Magnetic microcarriers • Modified C-60 fullerenes (bucky balls) • Hydrogel-type materials 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 25. Some Drug carriers… 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 26. Types of polymers • Polymer Microspheres : Two types – Reservoir type (drug is encapsulated-chocolate wrapper) – Matrix like (drug physically entrapped in a polymer network-cookie with chocolate crunch in between) • Polymers micelle may be single or polymeric micelle (hydrophobic and hydrophilic) 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 27. Polymer microspheres 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 28. Targeted drug delivery cont… Examples • Ocusert • Progestasert • Transdermal drug delivery / subcutaneuous delivery • Liposomes • Monoclonal antibodies • Erythrosomes • Dendrimers • Nanotechnology- nanosomes, nanorobots 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 29. Ocusert • Thin elliptical micro units containing drug in reservoir • Eg : Pilocarpine ocusert used in Glaucoma placed – Site : Under lower eyelid delivers the drug for a period of 7 days – Adv. – Pilocarpine is a short acting drug given 6th hrly is avoided. 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 30. 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology, KIMS Retisert – Fluocinolone acetonide – Rx non –infectious uveitis Gancyclovir – Rx of CMV retinitis Latanoprost
  • 31. Progestasert • Drug is entrapped in solid polymer i.e., silicon rubber and implanted or injected in to the body. • Progestasert : It is an IUCD inserted into uterus delivers progesterone at a constantly specified rate for 1yr. • ADV. : No missing of dose • DISADV. : Ectopic pregnancy – Chances of PID 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 32. Transdermal Adhesive Patch • Drug is incorporated into a polymer reservoir • Provides steady & smooth plasma conc. for a period of 1- 7 days • Site of application : Chest, Abdomen, Upper Arm, lower Back, Buttock Or Mastoid Region • Size : 5-20 cms and available in various shapes. • E.g. : Nitroglycerin, Nicotine, Estradiol, Hyoscine, Fentanyl 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 33. Transdermal Adhesive Patch cont… • Adv. – more convenient and better patient compliance • ADR : Local Irritation, Erythema • Disadvantage : Drug delivery is slow & passive, large molecular wt drugs cannot be delivered, lack of dosage flexibility. 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 34. Transdermal Drug delivery… • Iontophoresis : Galvanic current allows the penetration of drug applied to the skin into deeper tissues. – Anode iontophoresis - compounds with positive charge – Cathode iontophoresis – compounds with negative charge. – E.g. Salicylates • Laser-assisted Transdermal drug delivery 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 35. Special delivery forms in Subcutaneous route • Dermojet : Needle is not used. – A high velocity jet of drug solution injected using gun like implement and Solution gets deposited in subcutaneous tissue. – Essentially painless and suited for mass inoculations. – Eg. Insulin 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 36. Special delivery forms in SC route • Pellet implantation : Drug in solid pellet form introduced with a trochar and canula. – Provides sustained release of drug over weeks and months. Eg. DOCA, Testosterone 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 37. Special delivery forms in SC route cont… • Sialistic (Non biodegradable) and Biodegradable implants : Crystalline drug is packed in tubes or capsules made of suitable materials and implanted under skin. • NORPLANT - Levonorgestrel subdermally implanted provides contraception for a period of 5 yrs. ADV. : No missing of dose 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 38. Liposomes as Drug carriers • These are minute vesicles and consists one or more phospholipids bilayers. • May be unilamellar, multilamellar or multivesicular • Filled with non lipid soluble drugs and retained until liposome is disrupted. • Niosomes : similar to Liposomes but has non-ionic surfactants instead of phospholipids in the bilayer formation • Eg : Amphotericin, Daunorubicin, Doxorubicin, Azithromycin, Vincristine(approved in 2012) 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 39. 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 40. Advantages of Liposomes in DDS: • Increased stability and decreased toxicity of encapsulated drug. • Better pharmacokinetic, good therapeutic index. • Both hydrophilic and hydrophobic drugs can be carried. • Biologically inert, biodegradable, non- toxic, non-antigenic, non- pyrogenic. • Disadvantage: Highly expensive 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 41. Monoclonal antibodies • These are Antibodies produced by a single clone and are directed against a single antigenic determinant (epitope) • Mabs are produced on large scale using Hybridoma technique. 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology, Mouse inj. With Ag having epitopes a & b Expansion & elusion of MAb It produces B-lymphocytes to each epitope B1 B2 a b B1-My a B1-My a a a a a a The desired activated Bi fused with Myeloma cell in Polyethylene glycol Growth of hybridoma in HAT medium & cloning
  • 42. MAbs cont… • Murine MAbs not preferred now a days due to shorter half life and ability to induce allergic reactions • Chimeric MAbs : partly human and partly mouse antibody • Humanised MAbs –least Antigenic • In the name of Mabs the letter before mab indicates source of antibody i.e., “O” for murine (Muromonab) – “Xi” – chimeric (Rituximab, Abciximab) – “Zu” - human (Omalizumab, Pavlizumab) 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 43. Dendrimers • Dendritic macromolecules (highly branched, globular) : • Used to encapsulate individual small drug molecules (unimolecular nanocapsule) • Can also serve as “hubs” onto which large numbers of drug molecules can be attached via covalent bonds. • Eg. : Anticancer agents 5-fluorouracil to polyaminoamine dendrimers • Methotrexate to hydrazide-terminated dendrimers formed from poly aryl ether.3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 44. Dendrimer… 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 45. Bacterial ghosts/Artificial cells as carriers • Different species of microorganisms have been used to produce ghosts like Salmonella, Pasteurella hemolytica, Actinobacillus pleuropneumoniae, E.coli • Artificial Cells : Size & structure same as biological cell with some functional property of biological cells. • E.g. Microencapsulation of islets of pancreas, hepatocytes, cholesterol removing3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 46. 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology, Bacterial Ghost
  • 47. Hydrogel carriers • Hydrogels are hydrophilic, polymeric networks capable of imbibing large amounts of water or biological fluids. • Hydrogels are stimuli-sensitive gel systems modulate release in response to pH, temperature, ionic strength, electric field, or specific analyte concentration differences. 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 48. Micro Electro Mechanical System (MEMS) • Dorian Liepmann and Boris Stoeber developed MEMS syringe, the size of a fingernail. • It is pre-loaded with a lyophilized, or freeze-dried, drug stored in its silicone rubber reservoir. • The "shot/drug" is delivered by pressing the device against the skin for a few seconds. • The dry drug is pushed through the microneedles into the skin where the body's interstitial fluids assist in rapidly absorbing the drug directly into the bloodstream. 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 49. MEMS 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 50. Nano particles • Nanoparticles includes Nanospheres and Nanocapsules of size 10-200 nm which are solid particles, either amorphous or crystalline formed from biodegradable or non biodegradable polymers. • Nanocapsules : These are vesicular systems in which the drug is confined to a cavity surrounded by a unique polymer membrane • Nanospheres : These are matrix systems in which the drug is physically and uniformly dispersed.3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 51. Nanoparticles as carriers • Nanoparticles have many applications, including anti-tumour therapy, gene therapy, AIDS therapy, radiotherapy, in the delivery of proteins, antibiotics, virostatics, vaccines and as vesicles to pass the blood-brain barrier. 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 52. Nano - Erythrosomes as carriers • Drug loaded in body’s own erythrocytes. • Also called GOLDEN EGGS. ADVANTAGES: • Biocompatible • Nontoxic with minimum ADR. • Non-nucleated so large space available for drug incorporation. 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 53. Nano - Erythrosomes as carriers • Eg. : Insulin, L-asparginase, Heparin • Antiviral Agents: Acyclovir. • Cancer Chemotherapy drugs : Methotrexate, Bleomycin, Adriamycin. 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 54. Nanotechnology in healthcare… • Nanotechnology offers tools and techniques for more effective detection, diagnosis and Rx of diseases • Lab on chips help detection & diagnosis of diseases more efficiently • Nanowire help in early detection of cancer biomarkers 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 55. Nanotechnology in Cancer • The mixture of two different-sized nanoparticles work with the body's bloodstream to seek out, stick to and kill tumors. • One is designed to find the cancerous tumor and then adhere to it, while the second is designed to then kill the tumor cells.3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 56. Nano-Robots • Nano-Robots in treatment of cancer. 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 57. Magnetic Micro carriers • Include Magnetic Microspheres, Magnetic Liposomes, Magnetic Nanoparticles, Magnetic Resealed Erythrocytes, Magnetic Emulsion etc. • Magnetic Micro/Nanoparticle & molecular magnetic labels have been used for great number of application in various areas of biosciences, targeted drug delivery, imaging & in bio separation technology. 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 58. Future Challenges in nanotechnology – The main goals are to improve their stability in the biological environment – To mediate the bio-distribution of active compounds – The cytotoxicity of nanoparticles or their degradation products remains a major problem – Improvements in biocompatibility 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 59. Conclusion • NDDS – is for controlled & targeted delivery of drug for better absorption, site specific action with minimal adverse reactions. • Future of drug delivery influenced by micro fabrication / nanotechnology. • The question is how best to achieve this goal. 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,
  • 60. 3/23/2015 Dr Karuna Sree, Dept. Of Pharmacology,

Notes de l'éditeur

  1. Vapour pressure eg ; implanted infusion pump for heparin as anti coagulant therapy, morphine, in ca pain Mechanically – metered dose inhalers pH activated- encapsulated forms Hydrolysis-LHRH subdermal implant releases Goserelin for 1 month in Rx of prostatic Ca Enzyme – albumin micropshere encapsule of 5FU, released by action of protease enzyme Bio erosion – release of hydro cortisone with urase enz. Bioresponsive – glucose triggering insulin release Self reg.- insulin delivery system
  2. Insulin pump - also provided with glucose sensor devices which trigger the desired dose as per the body needs.
  3. Drug is incorporated into a polymer reservoir usually poly-isobutylene which in turn bonded to an adhesive plaster and delivered at skin surface by diffusion for percutaneous absorption into circulation.
  4. Mouse myeloma cells are first grown in a culture deficient in hypoxanthine phosphoribosyl transferase enzyme to inactivate Ag and prevent subsequent formation of immunoglobulins as tumour cell has specific antigen on its surface.
  5. The networks are composed of homopolymers or copolymers, and are insoluble due to the presence of chemical crosslinks (tie-points, junctions), or physical crosslinks, such as entanglements or crystallites.