COMPLETE DESCRIPTION ABOUT DENDRIMERS ALONG THEIR ROLE IN CURRENT MEDICAL SYSTEM,THEIR USEAGE IN CHEMOTHERAPUTIC PURPOSES ETC IS PROVIDED IN THIS PRESENTATION.

1. PHARMACEUTICS –VA
(Biopharmaceutics & Pharmacokinetics)

2. DENDRIMERS

3. INTRODUCTION

4. • Dendrimers are Nano-sized, radially symmetric molecules with a
well- defined, homogeneous, and monodisperse structure
that has a symmetric core, inner shell, and outer shell.
• In 1978, Fritz Vogtle, reported first dendrimer and the study of
dendrimers has been increased from last four decades.
• The highly well-defined polymers with three dimensional
branched structure are used in different biomedical and therapeutic
applications.
• Their chemistry playing very vital role in modern chemistry
studies, with multiple functions and distinct physicochemical
properties.
• Because of distinctive features of these polymers, they are mostly
used in Pharmaceutical, medicinal nanotechnology.

5. Conti….
• A variety of dendrimers exist and each has biological properties such
as poly-valence, self-assembly , electrostatic interactions, chemical
stability, low cytotoxicity, and solubility.
• It is mostly used in research studies by researchers due to their unique
properties.
• Dendrimers have improved the biocompatibility in the biological
system that are in vitro and in vivo.
• Dendrimers are nano carrier for drug delivery system in carrying
different therapeutic agents.

6. Properties of Dendrimers
● Dendrimers are a new class of compound(polymeric) materials . They are highly branched,
monodisperse macromolecules, and has a great impact on their physical and chemical
properties. They are suitable for a wide range of medical speciality and industrial
applications and their possible use in various areas of analysis, technology and treatment for
developing immunosensors.
● (1) Dendrimer-based FLISA was very effective in Arthropods borne virus detection.
● AuNPs-dendrimers were utilized to detect CA15-3 cancer markers in blood sample.
● PAMAM-based voltammetric immunoassay were used for detection of α-
Fetoprotein(serum glycoprotein).
● (2) Electrochemical immunosensors detected prostate-specific antigen. They can be
successfully used in cancer treatments as drug carriers due to covalent conjugation or by
physical enclosed.

7. §Conti…
. Dendrimers are increasingly used in oncological therapies . The implement of the use of
dendrimers in oncological therapies enables the delivery of drugs in an effective dose and
the observation of the effectiveness of anticancer therapy.(3)
The applications of dendrimers as drug and gene carriers, including
1) Active drug release strategies to separate gene from dendrimer in response to
stimuli.
2) Size-adaptive, charge reversal dendrimer delivery systems can better take head of
the size and surface properties of dendrimer
3)Bulk and micro dendrimer gel delivery systems.(4)

8. Synthesis of dendrimers
● Dendrimers are monodisperse polymers
grown in a fractal manner from a central point.
They are poised to become the cornerstone of
nanoscale devices in several fields, ranging
from biomedicine to light-harvesting.

9. Synthesis of dendrimers through
divergent Theorems:
● It is reported that a novel base-mediated
thioetherification of thioglycerol with
bromoesters, or the "Click" reaction, has been
developed bromoesters.

10. Synthesis of glycoporphrin dendrimers :
● Using convergent technique and click
chemistry, a series of porphyrin-cored
glycodendrimers with 8, 12, 16, and 24 -d-
glucopyranose units at the periphery have
been created.

11. ● In recent years dendrimers are in great demand for drug
delivery due to their property and characteristics of
structure. The formulation of dendrimers as nano-
carriers increases it’s water solubility, bioavailability
and increase drug delivery to a specific site. [1]
● The concept of click chemistry introduced by Sharpless
et Al. In 2001, consist of no of reactions that give
products with 100% yield. The most used click reaction
is CuAAC reaction.
Chemistry:

12. Conti…
The CuAAC reaction has many advantages, to prepare
unsymmetrical dendrimers that are difficult to obtain by any
other reaction. Dendrimers possess thiadiazole as a core,
triazole as branching unit and chalcones as terminal group.
Recently, click chemistry is in very demand and advanced
technology for synthesis of dendrimers in which small units
are joined together. Reagents easily available, and solvents
and advantages of click chemistry. Highly pure and excellent
yields are obtained as by Cu(1)-catalyzed click chemistry
reaction and by using chromatographic procedure [3]

13. Types of dendrimers

14. Ø Polyamidoamine (PAMAM) dendrimers
Ø Poly(propylene imine) (PPI) dendrimers
Ø Triazine dendrimers
Ø Citric acid dendrimers
Ø Polyester dendritic system
Ø Polyether dendrimers
Ø Phosphorous dendrimers
Ø Carbosilane dendrimers.

15. ● Poly(amidoamine) (PAMAM) dendritic nanostructures
for controlled site-specific delivery of acidic anti-
inflammatory active ingredient.
● PAMAM dendrimers are a family of highly branched
and mono-disperse synthetic macromolecules with
well-defined structures and compositions. Synthesis of
these nanocarriers can be carried out through the
divergent route
1.PAMAM

16. ● Poly (propylene imine) (PPI) dendrimer has recently received
remarkable attention due to its large surface area together
with the numerous functional groups present in its end,
which helps in binding biological materials or molecules. PPI
dendrimers are regarded as nanoscopic architecture and a
synthetic macromolecule with highly branched molecular
structure with a discrete number of functional end-groups.
Interestingly, these functional groups play significant roles in
the immobilisation of biological molecules
2.PPI

17. Method of analysis:
Dendrimers are spheroid polymeric
nanostructures that repeatedly branch
outward from an inner multimeric core.
2:Dendrimers are highly homogeneous
with very low polydispersity and in many
cases monodisperse.

18. Conti….
Three method use:
1-Nuclear magnetic resonance
2-Microscopy
3-Small angle X ray scattering

19. ØNuclear magnetic resonance:
Nuclear magnetic resonance is certainly the
most widely used routine analysis to
characterize dendrimers, but special techniques
have also been used to examine their size and
shape.

20. Conti….
Microscopy:
Two types of microscopy:
1-Transmission Microscopy
2-Scanning microscopy

21. Conti….
Small angle X ray analysis:
It provides information about their average radius of gyration
(Rg) in solution. Scattering intensity as a function of angle also
provides information on the arrangement of the polymer
segments, hence on the segment density distribution within the
molecule

22. Conti….
This technique applied:
fluorinated carbosilane dendrimers and
PAMAM dendrimers to afford their RG
values.

23. ● ROLE OF DENDRIMERS IN
NANOPARTICLES DRUG DELIVERY
AND ITS LIMITATIONS

24. ● Nano scale materials have unique properties
● The best dendrimer must have a low molecular weight to be
effortlessly filtered by the kidneys
● Drug molecules can be physically trapped inside the
dendrimers or be adsorbed on the dendrimer surfaces
● Drug molecules can also be covalently attached on the
dendrimer surfaces to provide dendrimer-drug conjugates
Dendrimers and various routes of drug
delivery

25. Conti…
Oral drug delivery:
● The oral route is mostly favored by patients and clinicians. For example peptidomimetics,
oral bioavailability is in the most of cases below passable levels
● An effective oral macromolecular drug carrier should have the capability to prevent the
drugs from degrading.
Occular drug delivery:
● Dendrimers have attracted remarkable attention as ocular drug delivery systems, because of
their tailorable structure, well-defined size and potentially favorable ocular biodistribution.
Transdermal drug delivery:
● The permeability of dendrimers via the skin is determined by physicochemical parameters
● Dendrimers are effective as transdermal drug delivery systems for NSAIDs, antimicrobial,
antiviral, anticancer.

26. Conti…
Targeted drug delivery:
● Targeted drug delivery is a technique of delivering a therapeutic agent to a specific cell
type or tissue in a site-specific manner. e.g: chemotherapeutics.
Magnetic Resonance Imaging (MRI):
● The most generally used MRI contrast agents are gadolinium-based contrast agents.
● The covalent attachment of Gd(III) complexes to PAMAM dendrimers to generate unique
macromolecular contrast agents for MRI.
Photodynamic therapy:
● PDT was planned as a helpful oncology tool more than 30 years ago, but it has restrictions.
● Diseased cells and tissues are destroyed by reactive oxygen species by using a combination
of light and photosensitizers.

27. ● Nanotechnology is a multidisciplinary scientific field. Nanotechnology advances in drug
delivery deal with the development of synthetic nanometer sized.
● Currently used drug delivery systems, such as liposomes, micelles, nanoemulsions,
polymeric nanoparticles and many others demonstrate a broad variety of useful
properties.
● They have a lot of advantages. As well as, they have disadvantages.
● So, each system was developed to overcome the disadvantages of another system.
● The last developed systems are SLN and NLC.
● SLN have been developed to eliminate each other’s disadvantages, SLN does not include
other systems disadvantages, but it provides all the advantages.
● Conclusion of this review, we found that solid lipid nanoparticles have the most
advantages in drug delivery systems, but nano lipid nanoparticles (NLC) have not been
disadvantages of SLNs.
● So, these systems have been developed in the future(1)
Advantages and Disadvantages

28. Therapeutic Application of dendrimers
Dendrimer effects on various pro-inflammatory mediators such as cyclooxygenase (COX)-1,
COX-2, nitric oxide and interleukin (IL)1β show that all these dendrimers (G4, G4-OH and G4.5)
have significant inhibitory effects on nitric oxide production in rat peritoneal macrophages.
The authors found that the in vivo anti-inflammatory activity of these
dendrimers was mainly due to the selective inhibition of COX-2; the inability to inhibit COX-1
further infers that dendrimers are potent and safe anti-inflammatory agents. Functionalised dendrimeric
structures as antimicrobial agents
The antibacterial activity of cationic dendrimers is due to the electrostatic interaction between
the negatively charged bacteria and the positively charged dendrimer. Dendrimer biocides are
bacteriostatic at low concentration by causing a slight change in membrane permeability. At a
higher concentration, they denature the membrane protein and begin to penetrate the lipid bilayer,
which causes the leakage of potassium ions. This leads to a complete breakdown of the bacterial
membrane and a corresponding bactericidal effect.

29. Antitumor effects of dendrites nanostructures
● Carbohydrate receptors and their ligands has proven useful in targeting and treating tumors,
● including breast and kidney melanomas. Changes in the exact collection of surface carbohydrates
● on cells showed the way for the process of malignant transformation. This trick has been
● explored to investigate immune responses against tumors. Prevention of scar tissue formation after
glaucoma surgery
● Glaucoma, a key cause of permanent blindness, can be treated surgically by creating a new
● channel to drain the ventricular fluid from the eye, reducing intraocular pressure and preventing
● damage to the optic nerve.
● Toxoplasmosis
● Toxoplasmosis is a parasitic infection caused by Toxoplasma gondii, an obligate intracellular
● Protozoan.
Conti…

30. §Role of dendrimers for cancer treatment
Activation of photosensitizer directly kill the tumor cells and
have
several advantages for other conventional cancer treatment
It is non invasive because irradiation is restricted to tumor
site
When it compare to other therapy it produce higher cure
Tumor consume high level of glucose than normal
cells phenomenon is know as warburg effect .

31. Conti...
Activation of photosensitizer directly kill the tumor cells and
have several advantages for other conventional cancer
treatment
● It is non invasive because irradiation is restricted to tumor
site
● PDT has widely applied against tumors to Which irradiation
can be applied such as breast, lungs neck and bladder
● When it compare to other therapy it produce higher cure
● Tumors consume high level of glucose than normal cells
phenomenon is know as warburg effect

32. ● IN CANCER CHEMOTHERAPY
Recently dendrimers are being used in cancer chemotherapy, as
nano carriers.
● TO TREAT BRAIN DISORDERS
Few invasive strategies, such as reversible disruption of the BBB
or direct delivery of drug-loaded nanocarriers, are effective but
suffer from a lack of patient compliance and other drawbacks.
Among the non-invasive strategies for systemic drug delivery
across the BBB, dendrimers have gained significant interest from
researchers
USE OF DENDRIMERS ACCCORDING TO
CURRENT RESEARCHES

33. ● TO TREAT INFECTIOUS DISEASES
They represent a very significant contribution in the field of
infectious diseases as a supplement to other therapeutic
approaches.Best example of dendrimer use In infectious
disease is its use to treat bacterial vaginosis.
● DENDRIMERS AS ANTIFUNGAL AGENTS
To some extent dendrimers also have anti funngal property
depending on its types (chemical structure)
They may directly affect the infectious fungi or may act as
adjuvants or carriers or as solubilizers etc
Conti...

34. ● We can conclude that dendrimers that can classified based on
the different types of generation and these generation
includes branching system
● Multiple steps are needed to produce a dendrimers and
resulting product will be macromolecules. Dendrimers are
very important for the detection of arthropods borne virus as
well as cancers marks present in a blood and
● involve in it’s treatment
Conclusion :

35. Conti....
● Dendrimer delivered through various routes which are
● Oral,occular, transdermal,targeted,MRI, photodynamic therapy
● Application of dendrimers include
● Antimicrobial effect
● Antiviral activity
● Antitumor effect
● Scar tissue prevention
● Parasitic infection prevention
● Toxoplasmosis

36. ● If we will see about the types of dendriems which are
basically
● 1.. dendriems having triazine
● 2.. having citric acid
● 3.. having polyester
● 4.. having phosphorus
● 5.. having carbosilans
● In short we can conclude that dendriems are very
diverse group and have Great demand in field and
produce 100% yield and also have Great scope