Drugs having pleiotropic effects, Neutraceuticals and Role of antioxidants in pharmacotherapeutics.

1. DRUGS HAVING PLEIOTROPIC EFFECTS
NUTRACEUTICALS
ROLE OF ANTIOXIDANTS IN PROPHYLAXIS AND THERAPY
Dr.Swaroopa, 2nd year PG,
Department of Pharmacology,
Rangaraya Medical College
1

2. DRUGS HAVING PLEIOTROPIC
EFFECTS
2

3. INTRODUCTION
• In pharmacology, pleiotropy includes all of a drug's actions other
than those for which the agent was specifically developed.
• These effects may be related or unrelated to the primary
mechanism of action of drug & they are usually unanticipated.
• It may include adverse effects which are detrimental ones, but is
often used to denote additional beneficial effects
3

4. Various drugs having pleiotropic effects
• Statins
• SGLT2 inhibitors
• Metformin
• Thiazolidinediones
• Cardio selective Glycosides
• Antithrombotic drugs
• Erythropoietin
4

5. STATINS
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• Reversibly inhibit HMG-CoA reductase.
• Binds to enzymes active site & block the substrate product
transition state of enzyme.
• All statins competitively inhibit the HMG-CoA reductase

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MEVALONATE PATHWAY

7. Pleiotropic effects of statins
7
• Cholesterol is an essential component of cell membrane & is the
immediate precursor of steroid hormones & bile acids.
• The rate limiting step of cholesterol biosynthesis in the liver is
HMG-CoA reductase
• Catalyses the conversion of HMG-CoA to Mevalonic acid

8. Pleiotropy of statins
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 Improvement of endothelial dysfunction
 Reduced inflammatory response
 Stabilization of atherosclerotic plaques
 Reduced thrombogenic response
 Antioxidant properties
 Inhibit vascular SMC proliferation
 Inhibit cardiac properties
 Decrease in the incidence of ischemic strokes

9. Statins & endothelial function
• Statins increase endothelial NO production by stimulating and
upregulating endothelial NO synthase(eNOS).
• Inhibition of RhoA by statins, mediates the increase in eNOS
expression.
• Prolong eNOS mRNA half-life.
9

10. Antioxidant effects
10
Inhibit the production of reactive oxygen species(ROS),such as
superoxide and hydroxyl radicals.
Statins attenuate angiotensin-2 induced free radical production
in vascular smooth muscle cells.
Inhibits Rac1 mediated NADH oxidase activity.
Downregulates angiotensin AT1receptor expression.

11. Statins & endothelial progenitor cells
11
Increase the number of circulating endothelial progenitor cells.
Statins induce angiogenesis
Promotes the proliferation, migration and survival of circulating EPCs
Rapidly mobilize EPCs from the bone marrow
Accelerate vascular structure formation
Effects via Activation of phosphatidylinositol 3-kinase(PI3K)/protein
kinase Akt and eNOS.

12. Statins & smooth muscle proliferation
12
Statins attenuate vascular proliferative disease.
Arresting cell cycle between the G1/S phase transition.
Inhibition of isoprenoid synthesis by statins decrease PDGF-
induced DNA synthesis in vascular SMCs

13. Statins and platelet function
13
Inhibition of platelet aggregation
Statin-mediated upregulation of eNOS
Reduction in the production of TXA2
Statins inhibit tissue factor expression by macrophages
Decrease cholesterol content of platelet and erythrocyte membranes.

14. Statins and plaque stability
14
Contains thrombogenic materials in the lipid core separated from
the bloodstream by a fibrous cap.
Secretion of proteolytic enzymes such as metalloproteinases by
activated macrophages may weaken the fibrous cap.
Plaque stabilization properties of statins are mediate through a
combines reduction in lipids, macrophages and MMPs(Matrix
Metalloproteinases).

15. Statins and vascular inflammation
15
Atherosclerosis is a complex inflammatory process.
Statins reduce the number of inflammatory cells in atherosclerotic
plaques.
Inhibition of adhesion molecules.
Reduced levels of C-reactive protein.

16. Effects of statins on myocardium
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 Inhibit cardiac hypertrophy.
Mechanism:
 Antioxidant mechanism involving inhibition of Rac1 geranylgeranylation.
 Statins inhibit angiotensin 2 induced oxidative stress.

17. Statins & ischemic stroke
17
 MOA:- attenuation of signalling pathways associated small GTP binding
proteins by inhibiting isoprenylation.
eNOS derived NO
NADPH oxidase & Ros
lipoprotein associated phospholipase A2 & CRP
Proinflammatory cytokines
Thrombaxanes A2
metalloprotein
Inhibition
 Decreases stroke risk & decreases ischemic damage volume

18. Statins & Dementia
18
Alzheimer's disease
MOA:- prevention of Rac and Rho isoprenylation, upregulation of the heme
oxygenase-1.
Effects:- dec oxidative stress & inflammation,
inc SOD activity,
inc eNOS
inc glutamatergic transporters
dec oxidized cholesterol
Therapeutic outcome :- improved cognitive function,
dec senile plaques
inc performance in mile to moderate AD subjects
dec development of AD.

19. PLEIOTROPIC EFFECTS OF SGLT2
INHIBITORS
19
SGLT2 INHIBITORS
MOA:-
• Inhibits the Na-glucose co-transporter
2 (SGLT-2) in the kidney to reduce
glucose reabsorption, resulting in
increased urinary glucose excretion,
and lower plasma glucose.
• SGLT-2 is expressed in the proximal
tubule and mediates reabsorption of
~90% of filtered glucose

20. SGLT2 INHIBITORS
20

21. Thiazolidinediones /Glitazones
21
• Used for the treatment of
type 2 diabetes.
• act by activating PPARs
(peroxisome proliferator-
activated receptors), a
group of nuclear receptors,
specific for PPARγ (PPAR-
gamma, PPARG)

22. Pleiotropic effects of TZDs
22
• Improves dyslipidaemias – dec TG, inc HDL
• Improves insulin sensitivity
• Reduce thrombotic markers – PAI-1, fibrinogen, platelet aggregation
• Reduce blood pressure
• Improve endothelial function
• Reduce inflammatory markers – CRP, IL-6, TNF-alfa, MCP-1
• Improve other vascular markers – MMP-9, VCM-1, ICAM-1, inhibits smooth muscle
proliferation, inhibits myocyte migration
• Adipocyte differentiation – inc adiponectin

23. METFORMIN
23
• Metformin is the first-choice therapy to lower hyperglycaemia
and manage type 2 diabetes.

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• Novel evidence suggests that
metformin reshapes the human
microbiota, promoting the growth of
beneficial bacterial species and
counteracting the expansion of
detrimental bacterial species.
• In turn, this action would influence
the balance between pro- and anti-
inflammatory circulating factors,
thereby promoting glycemic control
and healthy ageing.

25. Pleiotropic effects of anti-thrombotic drugs
25

26. Pleiotropic effects of Erythropoietin
26
 Erythropoietin is a
glycoprotein cytokine
secreted mainly by
the kidneys in
response to cellular
hypoxia; it stimulates
red blood cell
production in the
bone marrow

27. Pleiotropic effects of cardiac glycosides
27
 Cardiac glycosides are indicated for CHF, AF
 Pleiotropic effects :- Anti-cancer (lung, Breast),
Neuroblastoma, prostate
 MOA: pro-apoptopic effects, inhibiting Na+/K+ ATPase

28. NUTRACEUTICALS
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29. Nutraceuticals
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The term “Nutraceutical” was coined from “Nutrition” &
“Pharmaceutical” in 1989.
~ Stephen DeFelice, MD, Founder and Chairman, Foundation for Innovation in
Medicine (FIM), USA
Nutraceuticals can be defined as
“A food or part of food or nutrient, that provides health benefits,
including the prevention and treatment of a disease.”

30. 30

31. 31
nutraceuticals
Dietary
supplements
Functional food
& beverages
Vitamins &
minerals
Herbals
Protein
supplements
Probiotics
Functional food
Functional
beverages
Omega fatty acid
probiotic fortified
Energy drinks
Sports drink
Fortified drinks
Plant extracts
Ayurvedic
extracts
Algae extracts
Categories:-

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Nutraceuticals for
geriatrics
coenzymeQ10
Antioxidants
Polyphenols&
catechins
Carotenoids
phytosterols
B-vitamins
Whey proteins
Omega-3
fattyacids
Calcium & vit-D
Glucosamine
Chondroitin
Collagen
quercetin
Zinc
pre & probiotics
Potassium
Dietary fiber

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34. ROLE OF ANTIOXIDANTS IN
PROPHYLAXIS AND THERAPY
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35. Definition & importance
35
“Antioxidants are substances which counteract free radicals and
prevent the damage caused by them.”
• In recent years, antioxidants have gained a lot of importance
because of their potential as prophylactic and therapeutic agents in
many diseases.
• The discovery of the role of free radicals in cancer, diabetes,
cardiovascular diseases, autoimmune diseases, neurodegenerative
disorders, aging and other diseases has led to a medical revolution
that is promising a new paradigm of healthcare.

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• Free radicals are highly reactive molecules or chemical species
containing unpaired electrons that cause oxidative stress, which is
defined as “an imbalance between oxidants and antioxidants in favor of
the oxidants, potentially leading to damage”
• Oxidative stress can damage lipids, proteins, enzymes, carbohydrates
and DNA in cells and tissues
• resulting in membrane damage, fragmentation or random cross linking
of molecules like DNA, enzymes and structural proteins and even lead
to cell death induced by DNA fragmentation and lipid peroxidation

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• These consequences of oxidative stress construct the molecular
basis in the development of cancer, neurodegenerative
disorders, cardiovascular diseases, diabetes and autoimmune
disorders.
Human antioxidant defense is equipped with enzymatic
scavengers like superoxide dismutase (SOD), catalase (CAT)
and glutathione peroxidase; hydrophilic scavengers like urate,
ascorbate, glutathione and flavonoids; lipophilic radical
scavengers such as tocopherols, carotenoids and ubiquinol.
The defense also comprises enzymes involved in the reduction
of oxidized forms of molecular antioxidants like glutathione
reductase, dehydroascorbate reductase.

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 In disease conditions, the defense against ROS is weakened or
damaged and the oxidant load increases.
 In such conditions, external supply of antioxidants is essential to
countervail the deleterious consequences of oxidative stress.

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ROLE OF OXIDANTS IN VARIOUS DISEASES
DISEASE ROLE OF FREE RADICALS IN PATHOPHYSIOLOGY
1. Atherosclerosis Superoxide-mediated endothelial dysfunction, activation of
macrophages
2. Myocardial infarction ROS driven ischemic reperfusion injury and myocyte
necrosis and/or apoptosis
3. Hypertension ROS-mediated vascular smooth muscle cell proliferation,
oxidant production via NADH/NADPH oxidase and
endothelial dysfunction
4. Diabetes ROS accelerated formation of advanced glycation end
products (AGEs) Superoxide-mediated endothelial
dysfunction
5. Aging Cell damage and metabolic abnormalities
6. cancer ROS-mediated gene mutations (modification of pyridine and
purine bases) and post-translational modifications leading
disruption of cellular processes

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DISEASE ROLE OF FREE RADICALS IN PATHOPHYSIOLOGY
7. Parkinson's disease ROS-mediated mitochondrial dysfunction
8. Alzheimer's disease Amyloid peptide and advanced glycation end products.
ROS-mediated neurotoxicity to hippocampal cells and the
synaptosomal membranes
9. Huntington's chorea ROS-mediated transcriptional dysregulation and
mitochondrial impairment
10. Auto immune disorders ROS-mediated inflammation and tissue destruction
11.Age-related macular
degeneration
Photochemical reactions in the oxygen-rich environment of
the outer retina lead to the liberation of cytotoxic (ROS)
12. Acute lung injury, acute
respiratory distress syndrome,
inflammation and hyperoxia
ROS-mediated inflammation and endothelial dysfunction

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Some selected
antioxidants and their
mechanisms of action
SOD = superoxide dismutase, CAT = catalase, NAC
=N-acetyl cysteine, GSH = glutathione, EGCG =
epigallocatechin-3-O-gallate, CoQ10= coenzyme
Q10, I3C =indole-3-carbinol.

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Role of pharmaceutics in development of antioxidants

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Antioxidants in diet:-
 Evolution of human diet reveals that the modern day intake of
antioxidants is far less from our ancients.
 The organized agriculture which had instigated some thousands of years
ago started depriving us from the antioxidant-rich diet constantly.
 Human antioxidant defense system is incomplete without dietary
antioxidants.

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 Humans lack the ability to synthesize ascorbic acid endogenously, for
which we have an absolute requirement.
 The ascorbic acid needs can be met only by the dietary sources.
 Apart from ascorbic acid other antioxidants like vitamin E, CoQ10,
carotenoids and polyphenols are obtained from external sources and play
an important role in maintaining human health.

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Physicochemical and biopharmaceutical properties
Dose, solubility, permeability, stability, bioavailability and pharmacokinetic
parameters absorption, distribution, metabolism and excretion are the
important properties that affect the fate of drugs through oral route.
Solubility and permeability of drugs can be correlated to their absorption
through gastrointestinal tract.
According biopharmaceutical classification these two are the main
parameters affecting the oral bioavailability.

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 While designing a dosage form for any drug candidate,
it is important to consider the solubility, permeability and pre-systemic
loss as major contributors for the drugs having poor bioavailability
That could help in successful design of the suitable dosage form or
delivery system which can markedly improve the drug's performance
through oral route.

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DOSE:-
Gives a fair idea of potency.
The dose is inversely proportional to the bioavailability of a compound.
The first and foremost step in a formulation design is the pre-formulation
study, which will provide the factors influencing the bioavailability and in
turn potency
SOLUBILITY:
 Solubility enhancement can be achieved by increasing the available
surface area by particle size reduction, complex formation, micelle
formation, etc,.

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 Solubility of antioxidants is very diverse depending on the class, source
and type of conjugation.
eg:
EGCG is considered to be less soluble compound among green
tea catechins.
 The solubility of highly soluble drugs can be modulated to sustain
release or prolong the activity; eg: vitamin C
Coenzyme Q10 is practically insoluble attributing to its
lipophilic10 carbon chain

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PERMEABILITY:
 Permeability through the GIT is one of the major factors affecting the
performance of drugs administered through oral route. Permeability of
the compound mainly depends on the partition coefficient.
 Unfortunately, permeability, remained unaddressed in the case of
several antioxidants, which are being evaluated for the improvement
of human health.
Stability:
Many of the antioxidants are unstable in aqueous solutions.

51. 51
Bioavailability:-
• It is mainly dependent on the solubility, permeability as well as the
stability in the GIT and biotransformation before reaching the blood
through oral route.
• Most of the carotenoids including lycopene, when administered along
with high-fat diet result in better bioavailability.
• CoQ10's bioavailability is only 10% from meal and oil suspension
because of the poor solubility and permeability of the drug.

52. 52
Vitamin C has good bioavailability when administered in small
doses; however the bioavailability decreases with increase in
dose.
At 200 mg dose, the bioavailability was 100%, but as the dose
was increased up to 1250 mg the bioavailability was decreased
below 50%. This may be because of the urinary excretion, which
is increased with the dose.

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DELIVERY APPROACHES
1) Conventional delivery:-
• Conventional dosage forms usually consist of tablets, capsules and
liquid orals through the most acceptable oral route. These conventional
forms are easy to formulate and are relatively less expensive.
• Antioxidant enzymes are generally administered through intravenous
route.
• At times, these dosage forms lead to loss of efficacy of the active agent
which may be due to various reasons like poor bioavailability, first pass
effect or instability of the active agent in GI tract.

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Vitamins have been formulated mainly into tablets and capsules.
Generally, these agents were found in combinations rather than individual
products.
Vitamin C especially has been reported to be stable in the tablets at least for
20 weeks.
Storage at 25 °C or daily opening of bottles stored at room temperature
resulted in 0–2% loss of ascorbic acid.

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• Vitamin C has relatively less bioavailability problems in comparison
to other antioxidants, but the elimination was reported to be very
rapid for this agent and absorption is saturable.
• For this reason, sustained release formulations have been
developed for vitamin C
• Other antioxidants like EGCG, quercetin, lycopene, ellagic acid and
CoQ10 are difficult to deliver by these conventional dosage forms.
• Many of these are not formulated in the pure forms; instead the plant
extracts of these agents are generally formulated and marketed.

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• The choice of dosage form is affected by the properties
of the molecule, cost of dosage regimen, patient
compliance and intended use in prophylaxis or therapy.
• Prophylaxis desires oral dosage forms, which can act
for prolonged periods of time.

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2) Inclusion complexes:-
• Cyclodextrins (CDs) are cyclic α(1–4) linked glucose oligomers.
• CD molecules easily form inclusion complexes with a wide variety
of molecules and molecular ions.
• These complexes were employed to increase the aqueous
solubility of drugs and the stability of labile drugs resulting in
improved bioavailability.
• Lycopene and CoQ10 are among the major lipophilic antioxidants,
solubility of which has been increased using inclusion complexes

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3)Chemical modifications:-
Numerous modifications of endogenous as well as exogenous
antioxidants have been attempted in order to
(i) prolong the half-life of these agents in vivo,
(ii) get more stable derivatives,
(iii) protect these agents from degradation/ inactivation in GIT and reduce
their immunogenicity, and
(iv) attain targeting to the tissues or cells

59. 59
• Coupling of polyethylene glycol (PEG) to the antioxidant
enzymes increases their bioavailability and enhances their
protective effect.
• In particular, the coupling of SOD and CAT amino groups with
PEG minimizes their elimination by the reticuloendothelial system
and prolongs their circulation by increasing their half-lives from
few minutes to several hours in rats and mice.
• Chemical modification of ascorbic acid has led to more stable
derivatives such as ascorbyl esters with C6 to C18 fatty acids or
ascorbyl phosphate salts.

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• In case of vitamin E, the acetate and acid succinate esters are
commonly used clinically for their high stability.
• The hydrochloride salt of D-α-tocopheryl N,Ndimethylaminoacetate
is another prodrug of vitamin E which has high solubility and
stability.
• Vitamin E succinate was coupled to PEG similarly as enzymatic
antioxidants to improve the efficacy

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4)Novel drug delivery systems:-
• Delivery systems help compounds to be delivered in efficient manner
rather than altering their chemical nature or biological activity.
• Sometimes, chemical modifications may not help for the efficient delivery.
• little or no changes in drug's properties are observed when delivered
through the delivery systems.
• This facilitated the doorway of novel delivery systems in the development
of antioxidants.

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• For the drug to have better efficacy, it should reach the site of action,
for example drugs should cross blood brain barrier to treat
neurodegenerative disorders and target the malignant tumors in
treatment of cancer.
• Novel drug delivery systems would make antioxidant reach site of
action and improve the efficacy of therapy, generally by improving
the bioavailability.
• These delivery systems are applicable to overcome various
pharmacokinetic problems associated with antioxidants.

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COMPARISION

64. 64
5)Self-emulsifying drug delivery systems (SEDDS) :-
• SEDDS offer the potential for enhancing the absorption of poorly
soluble and/or poorly permeable compounds through oral route.
• SEDDS were shown to improve the delivery of lipophilic compounds
such as CoQ10 by the oral route.
• Following oral administration, SEDDS provided a two-fold increase in
the bioavailability compared to a powder formulation.
• For drugs that are poorly soluble and/or poorly permeable, a significant
improvement in reproducibility in performance and bioavailability might
be achieved with SEDDS.

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6) Liposomes :-
 Liposomes are potential systems for drug delivery because of their size,
hydrophilic and hydrophobic character and biocompatibility.
 Properties of liposomes are very versatile and vary with lipid
composition, size, surface charge and method of preparation.
 Lectin modification of liposomes promotes binding to Peyer's patches in
the GIT and facilitates delivery of the agents loaded in the liposomes
through oral route.
 Antioxidant liposomes hold great promise in the treatment of many
diseases in which oxidative stress plays a significant role.

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 The intra-tumor administration of liposomes is a highly effective
approach for the treatment of local solid tumors.
 Liposomes of catechin, epicatechin and EGCG were prepared and
shown that the these preparations are retained for longer durations
in the tumor in comparison to aqueous solutions of these agents.
 Liposomes of vitamins C and E were used in combination or
individually and reported that liposomal antioxidants were able to
prevent the ischemia and reperfusion where the free forms of
antioxidants failed or showed little effect.
 This could be because of the faster penetration rate of the liposomal
antioxidants into the brain cells than the free forms.

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7) Microparticles:-
 Microparticles have been designed and evaluated as delivery
systems for both endogenous as well as exogenous antioxidants.
These particles are either matrix type entrapping the active moiety or
capsule type encapsulating the drugs.
 Administration of EA microspheres (mcEA) to rats, reduced the
severity of dextran sulfate sodium (DSS) induced colitis in a dose-
dependent manner, and a significant effect was observed at 10
mg/kg, the ED50 being 2.3 mg/kg.
 This suggests that ellagic acid microspheres can be used to treat
ulcerative colitis through oral route effectively.

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8) Nanoparticles:-
 Nanoparticles are colloidal particles varying in size from 10 nm to 1000 nm.
 Either direct nano sizing of drug or incorporation into lipidic and polymeric particles
can help deliver drugs with poor aqueous solubility and permeability
 After oral administration, these particles also protect the drug from GI degradation.
In recent years, the focus is on developing biodegradable polymeric nanoparticles
for drug delivery.
 These particles apart from increasing the bioavailability provide sustained release
of drug.
 Antioxidants like EGCG and ellagic acid which have marked anti-cancer activity
would benefit in terms of efficacy and patient compliance when delivered by
means of nanoparticles.

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• In case of the drugs where efflux mechanisms play major role in poor
oral bioavailability, these nanoparticles will help to improve their
bioavailability by virtue of the unique absorption mechanism through
lymphatic system.
• Literature also suggests that polysorbate 80 coated nanoparticles can
cross blood brain barrier and deliver the drug to brain.

70. 70
9) Gel-based systems:-
 An alternative and promising research field deals with particles obtained from hydrogel
systems.
 The hydrogels may be sensitive to environmental stimuli such as pH, ionic strength,
electric/magnetic fields, light and temperature depending on the substrate used.
 Thermo responsive gels for the controlled delivery of vitamin E had been shown to
release the drug in a controlled fashion.
 These gel based systems could help in encapsulating antioxidants for sustained
release..

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10) Targeting approaches :-
The delivery of antioxidants to tissue or organ of interest is not
possible by the conventional delivery approaches.
To attain the delivery of these agents to the sites where they are
required, many targeting approaches have been adopted.
Targeted drug delivery promises a significant improvement over the
current therapeutic means and, therefore, has remained the focus of
intense research.

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The blood–retina barrier and the extra ocular epithelia represent the
obstacle in the drug delivery to the choroid, retina, and vitreous.
Only a fraction of the drug administered orally or by subcutaneous or
intramuscular routes reaches the retina, requiring large doses to be
therapeutically effective.
 A possible approach to improve retinal drug delivery is to facilitate
localized delivery to the posterior segment of the eye by using Anopore
nanoporous filter.

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11) Novel methods to treat oxidative stress
Gene therapy in contrast to the delivery of human recombinant
antioxidant enzymes makes the antioxidant therapy free of immune
reactions.

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Antioxidants and their functions
The food factor was named “Vitamin A” in 1920. It comes in two
different sources:
1. Retinol and retinoids
2. Carotenoids
The vitamin A is usually used to refer to both the metabolically
active form (retinol) and other chemical forms that are converted
into retinol within the body (carotenoids).
Retinol is called preformed vitamin A and the carotenoids, of
which beta carotene is most active are called provitamin A
PROTECTIVE ROLES OF ANTIOXIDANTS IN CARCINOGENESIS

75. 75
Beta-carotene
1. Precursor of Vitamin A.
2. Anti-oxidant and free radical
scavenging.
3. It immunomodulate and stimulate
production of T-helper and NK cells
and IL-2 receptors.
4. Inhibition of mutagenesis
5. Inhibition of cancer cell growth
Vitamin A (retinoids)
1. Inhibits keratinization and terminal
differentiation of epidermal cells.
2. Enhancement of cellular
immunity.
3. Arrest/reverse leukoplakia
progression.
4. Induction of cytotoxic and
cytostatic effects on cancer cells.
5. Influence DNA, RNA, and gene
expression.
6. Interfere with carcinogenic
stimulation and binding.

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Vitamin E (A-tocopherol)
1. Scavenger of free radicals.
2. It maintains the integrity of membrane and immune function.
3. It inhibits the cancer cell growth and differentiation.
4. Has role in inhibition of mutagenicity and formation of nitrosamines.
5. In cancer cells it inhibits DNA, RNA and protein synthesis.
6. Cytotoxicity

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Vitamin C (ascorbic acid)
1. Has potent antioxidant activity
2. It inhibits vitamin E degradation.
3. It reduces the formation of nitrosamines.
4. Reduces oncogene expression.
5. It has also plays a important role in enhancement of detoxification
via cytochrome P450
6. Blocks formation of fecal mutagens.

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CONCLUSION
 Antioxidants are molecules with multifunctional activities in various diseases, unlike the drugs in
current use which serve for specific disease.
 Therefore, considering the therapeutic potential of the antioxidants, there is every need to
implicate novel drug delivery technologies to improve their performance.
 It has been estimated that more than two-thirds of human cancers, which are contributed by
mutations in multiple genes, could be prevented by modification of lifestyle including dietary
modification.
 Increasing understanding of the free radicals role in diseases is opening new area for the
antioxidants to manifest in prevention and therapy of the healthcare system, along with promising
role as supportive remedies in many regimens of mainline therapy.
 However, more number of animal and human studies are required to establish the efficacy and
safety of these agents in various chronic and or acute oxidative stress related diseases.

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79
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81. THANK YOU
81