ICT Role in 21st Century Education & its Challenges.pptx
Drug targeting
1. A seminar on
Targeted Drug Delivery
Presented by,
Deshpande Suraj S.
M.Sc Second Year
Department of Microbiology
Government Institute of science, A’bad
2. What is targeted drug delivery?
Targeted drug delivery, sometimes called smart drug delivery, is a method of delivering
medication to a patient in a manner that increases the concentration of the medication in
some parts of the body relative to others.
The nanoparticles loaded with drugs and targeted to specific parts of the body where there
is solely diseased tissue, thereby avoiding interaction with healthy tissue.
Targeted delivery is believed to improve efficacy while reducing side-effects.
The advantages to the targeted release system is the reduction in the frequency of the
dosages taken by the patient, having a more uniform effect of the drug, reduction of drug
side-effects, and reduced fluctuation in circulating drug levels.
3. • There are Two kinds of targeted drug delivery: active targeted drug delivery, such
as some antibody medications, and passive targeted drug delivery, such as the
enhanced permeability and retention effect (EPR-effect).
• In passive targeting, the drug’s success is directly related to circulation time.
This is achieved by cloaking the nanoparticle with some sort of coating.
• Active targeting of drug-loaded nanoparticles enhances the effects of passive
targeting to make the nanoparticle more specific to a target site.
• There are several ways that active targeting can be accomplished. One way to
actively target solely diseased tissue in the body is to know the nature of a
receptor on the cell for which the drug will be targeted to. Researchers can then
utilize cell-specific ligands that will allow for the nanoparticle to bind specifically
to the cell that has the complimentary receptor.
4. There are different types of Drug delivery vehicles, such as polymeric micelles, liposomes,
lipoprotein-based drug carriers, Nano-particle drug carriers, dendrimers, etc.
• An ideal drug delivery vehicle must be non-toxic, biocompatible, non-immunogenic,
biodegradable, and must avoid recognition by the host's defence mechanisms.
• The most common vehicle currently used for targeted drug delivery is the liposome.
• A liposome is a tiny vesicle consisting of an aqueous core entrapped within one or more
natural phospholipids forming closed bilayered structures.
• Liposomes are non-toxic, non-hemolytic, and non-immunogenic even upon repeated
injections; they are biocompatible and biodegradable and can be designed to avoid clearance
mechanisms (reticuloendothelial system (RES), renal clearance, chemical or enzymatic
inactivation, etc.)Lipid-based, ligand-coated nanocarriers can store their payload in the
hydrophobic shell or the hydrophilic interior depending on the nature of the drug/contrast
agent being carried.
5. • Examples of Conventional Liposomes: 1,2-distearoryl-sn-glycero3-phosphatidyl
choline (DSPC), sphingomyelin, egg phosphatidylcholine, and
monosialoganglioside.
Figure: Schematic representation of liposome-based systems. (a) Conventional liposomes. (b) Stealth liposome coated with a
polymeric conjugate such as PEG. (c) Stealth liposome coupled with a functionalized ligand. (d) Liposome with a single ligand and
antibody. (e) Duplicated ligand with repeated peptide sequence. (f) Liposome loaded with perfluorocarbon gas (adapted from
Zucker et al).
(a) (b) (c)
(d) (e) (f)
7. TargetingtumourcellsbyusingLiposome(AMagicBullet):
• Various strategies have been adopted for targeting liposomes to the tumor
sites.
[A] Passive Targeting:
• Owing to the leaky nature of the tumor-associated blood vessels,
biomacromolecules and nanosized drug delivery systems readily translocate
across the capillary endothelium and enter the interstitial space.
• Solid tumors lack adequate lymphatic drainage that leads to a
nanopreparation's accumulation in the tumor microenvironment known as
enhanced permeability and retention effect.
• The accumulation of liposomes in the tumor strongly depends on the size of
the endothelial gaps in the capillary vasculature for a particular cancer. To
utilize the EPR effect, the liposomes should usually be smaller than 400 nm
in size.
• Anionic or neutral liposomes escape from renal clearance and the cationic
liposomes interact with the anionic species in the blood, resulting in rapid
clearance from circulation by the RES, which reduces the EPR effect.
9. [B] Active Targeting: (Targeting cancer cell surface receptors)
• The most common strategy to target overexpressed cell surface receptors on cancer cells
is the use of receptor-specific ligands or antibodies.
• Active targeting via cell surface receptor targeting has been explored widely in cancer
since many cancer cell types display upregulation of tumor-specific receptors. For
example, TfRs and folate receptors (FRs) are greatly overexpressed by many tumor cell
types in response to their increased metabolic demand.
Targeting FRs:
• Folic acid has recently been used as a targeting ligand for specialized drug delivery owing
to its ease of conjugation to nanocarriers, its high affinity for FRs and the relatively low
frequency of FRs, in normal tissues as compared with their overexpression in activated
macrophages and cancer cells.
• FRs are overexpressed in certain ovarian, breast, lung, colon, kidney and brain tumors.
• Folate-linked nanoparticles deliver their cargo(drug) intracellularly through receptor-
mediated endocytosis.
11. • The attachment of folate directly to the lipid head groups is unfavorable for intracellular
delivery of folate-conjugated liposomes, since they do not efficiently bind to cells expressing
FR. By contrast, folate attached to the liposomal surface by a PEG spacer arm enters cancer
cells very efficiently.
• Several folate-conjugated liposomal systems have been reported which have the higher
cytotoxicity than unmodified plain liposomes. Examples: Folate-GSH-PEG-DSPE, doxorubicin-
loaded PEGylated liposomes, etc.
12. Product name Drug Indications Status Ref.
Approved drugs
Doxil®/Caelyx® (Janssen
Pharmaceuticals, NJ, USA)
Doxorubicin
AIDS-related Kaposi's sarcoma, recurrent
ovarian cancer, metastatic breast cancer and
multiple myeloma
Approved [114]
Lipusu® (Luye Pharma
Group Ltd, Shanghai,
China)
Paclitaxel Solid tumors Approved [115]
DaunoXome® (Galen Ltd,
Craigavon, UK)
Daunorubicin Kaposi's sarcoma Approved [116]
Myocet® (Enzon
Pharmaceuticals, NJ, USA)
Doxorubicin Metastatic breast cancer Approved [117,118]
Lipo-dox® (Sun Pharma,
Mumbai, India)
Doxorubicin Kaposi's sarcoma, breast and ovarian cancer Approved [119,120]
Marqibo® (Talon
Therapeutics, CA, USA)
Vincristine Acute lymphoblastic leukemia Approved [121–123]
Products in clinical trials
EndoTAG®-1 (Medigene,
Martinsried, Germany)
Paclitaxel
Antiangiogenic properties, breast cancer,
pancreatic cancer
Phase II [124,125]
Atragen™ (Aronex
Technologies Inc., KS,
USA)
Tretinoin Acute promyelocytic leukemia,
hormonerefractory prostate cancer
Phase II [124]
Lipoplatin™ (Regulon Inc.,
CA, USA)
Cisplatin
Pancreatic cancer, head and neck cancer,
breast and gastric cancer and non-squamous
non-small-cell lung cancer
Phase III [124,126–
128]
SPI-077 Cisplatin Head and neck cancer, lung cancer Phase I/II [124,129,130]
ThermoDox® (Celsion, NJ,
USA)
Doxorubicin Primary hepatocellular carcinoma
Colorectal liver metastasis
Phase III
Phase II
[131–133]
Table: Liposome-based drugs marketed and in clinical development for cancer therapy.
13. References
1. Deshpande P.P., Biswas S., Torchilin P.V., Currents trends in the use of liposomes for tumor
targeting, Nanomedicine(Lond.), Sept.2013;8(9).
2. Mufamadi M.S., Pillay V., choonara Y.E., Lisa C., Modi G., Naidoo D., A review on composite
Liposomal technology for specialized drug delivery, Journal of drug delivery, volume 2011,
ID939851.
3. Samad A., Sultana Y., Aquil M., Liposomal drug delivery system: An update review, Current
drug delivery, 2007,4, 297-305.
4. Basu M.K., Liposomes in drug targeting, Biotechnology and Genetic engineering reviews,
volume12, December1994.UK.
5. Mishra P., Nayak B., Dey R.K., PEGlyation in anticancer therapy: An overview, Asian Journal
of Pharmaceutical sciences, Volume11, issue3, june2016, 337-348.
6. Singh B.D., Biotechnology: Expanding Horizons, fourth edition, kalyani publishers, New
Delhi, 479-481.
