1. PROTEIN AND PEPTIDE
DRUG DELIVERY SYSTEM
PRESENTED BY
BRAJESH KUMAR
M. PHARM (1ST YEAR)
PHARMACEUTICS
BBAU LUCKNOW
,
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2. Contents
I. Protein & Peptides
II. Structure of protein
III. Classification of protein
IV. Drug delivery system
V. Stability testing
VI. Conclusion
VII. References
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3. 1. Protein & Peptides
 PROTEINS: Proteins are the large organic compounds made
of amino acids arranged in a linear chain and joined together by
peptide bonds.
Protein > 50 amino acids
 PEPTIDES: These are short polymers formed from the linking,
in a defined order of amino acids.
peptide < 50 amino acids
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 Why protein and peptide are used;
 The protein and peptides are very important in biological cells.
 Lack of proteins and peptides causes diseases like Diabetes
mellitus.
 Diabetes mellitus is caused due to the lack of protein called
INSULIN.
 Now a days R-DNA technology and hybridoma techniques also
used in protein and peptide based pharmaceuticals.
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ADVANTAGES
 Erythropoietin used for production of RBC.
 Tissue plasminogen activator is used for Heart attack, Stroke.
 Oxytocin maintain labor pain.
 Bradykinin increases the peripheral circulation.
 Somatostatin decrease bleeding in gastric ulcer.
 Gonadotropin induce ovulation.
 Insulin maintain blood sugar level.
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FUNCTIONS
 Transport and storage of small molecules.
 Coordinated motion via muscle contraction.
 Mechanical support from fibrous protein.
 Generation and transmission of nerve impulses.
 Enzymatic catalysis.
 Immune protection through antibodies.
 Control of growth and differentiation via hormones
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7. 2. Structure of protein
The structure of protein divided in to four types:
1. Primary structure : The amino acid sequence.
2. Secondary structure: Regularly repeating local structures
stabilized by hydrogen bond.
3. Tertiary structure : Three dimensional structure of
polypeptide.
4. Quaternary structure: The structure formed by several protein
molecules (polypeptide chains).
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9. 3. Classification of protein
 Depending on the number of amino acids they are classified as
follows:
 Polypeptides protein
 Oligopeptides protein
 Fibrous proteins
 Globular proteins
 Oligo meric proteins
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10. 4. Delivery of proteins
DRUG DELIVERYCLASSIFICATION
Pulmonary Parenteral Transdermal
Implants Ocular Nasal
Miscellaneous Oral
Route ofAdministration
PEGylation Pro-drug Polymerdepot
DrugModification
DrugDelivery
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Parenteral routes of administration;
 Parenteral route is most efficient way for systemic delivery of
proteins and peptides.
 This is the best choice to achieve therapeutic activity
 Mainly 3 routes of administration
 Intravascular
 Intramuscular
 Subcutaneous
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Advantages
Route of delivery for 95% of proteins
Allows rapid and complete absorption .
Avoids first pass metabolism
Disadvantages
Problems with overdosing, necrosis
Local tissue reactions/hypersensitivity
Everyone hates getting a needle
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INTRAVENEOUS ROUTE:
 Excessively metabolized and tissue drug bound at the site of
IM can be administered by this route such as Insulin ,
Interferon etc.
DISADVANTAGES:
Causes pain, tissue necrosis and thrombocytopenia.
ADVANTAGES: Antibiotics can be administered.
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 INTRAMUSCULAR ROUTE:
 Gamma globulins given by this route are proved to have long-
term protection from hepatic infection. some drugs given by this
route include long acting insulin, GH.
DISADVANTAGES:
Not used for all proteins and peptide drugs because of
metabolism of drugs at the site of injection.
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 SUBCUTANEOUS ROUTE;
 Controlled release is obtained from implantable polymeric
devices.
 These are prepared from crossed linked polymers which are
biocompatible and biodegradable e.g. Poly lactic acid.
Release of Insulin, bovine serum albumin, LH was prolonged by
this route.
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16. 4. PARENTERAL DRUG DELIVERY SYSTEM
 Polymer based drug delivery system.
 Liposome based drug delivery system.
 Hydro gel based drug delivery system.
 Emulsion based drug delivery system.
PUMPS:
 Implantable infusion pumps
 Mechanical pumps
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18. Parenteral routes of administration
 Parenteral route is most efficient way for systemic delivery of
proteins and peptides.
 This is the best choice to achieve therapeutic activity.
 Mainly 3 routes of administration
 INTRAVASCULAR
 INTRAMUSCULAR
 SUBCUTANEOUS
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19. • Route of delivery for 95% of proteins
• Allows rapid and complete absorption .
• Avoids first pass metabolismAdvantages
• Problems with overdosing, necrosis
• Local tissue reactions/hypersensitivity
• Everyone hates getting a needleDisadvantages
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20. INTRAVENEOUS ROUTE
 Excessively metabolized and tissue drug bound at the site
of IM can be administered by this route.
EX: Insulin, Interferon.
DISADVANTAGES:
 Causes pain, tissue necrosis and thrombopenia.
ADVANTAGES:
 Antibiotics can be administered.
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21. INTRAMUSCULAR ROUTE
 Gamma globulins given by this route are proved to have long-
term protection from hepatic infection.
 some drugs given by this route include long acting insulin, GH.
DISADVANTAGES:
 Not used for all proteins and peptide drugs because of
metabolism of drugs at the site of injection.
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22. Subcutaneous route
 Controlled release is obtained from implantable polymeric
devices.
 These are prepared from crossed linked polymers which are
biocompatible and biodegradable.
EX: polylactic acid
 Release of Insulin, bovine serum albumin, LH was prolonged by
this route.
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23. Parenteral drug delivery system
 Polymer based drug delivery system.
 Liposome based drug delivery system.
 Hydro gel based drug delivery system.
 Emulsion based drug delivery system.
PUMPS:
 Implantable infusion pumps
 Mechanical pumps
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25. Polymer based drug delivery system
polymers are used as carriers in this drug
 Pug delivery system.
CHARACTERS OF POLYMERS
 It should be biodegradable.
 It should be bio compatible.
 And non-toxic.
Two types of polymers are used widely
 natural polymers
 synthetic polymers
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26.  Natural polymers: Collagen , hemoglobin and gelatin.
 Synthetic polymers: mainly poly esters like PLA and PGA are
used widely.
 Diffusion of drug out of the polymer
 Drug Release by Polymer Degradation
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27. Liposome based drug delivery
 Spherical vesicles with a phospholipid bilayer
 Liposome's are microscopic vesicles composed of one or more
aqueous compartments.
Liposome’s in Proteins delivery :
 Example: Lecithin used in controlled drug release.
Liposome’s in peptide drug delivery:
 Bleomycin : A peptide with anti tumor activity, reduces normal
tissue toxicity.
 Negatively charged liposome's produces a prolonged
hypoglycemic effect in diabetic drugs, which are injected by
subcutaneous injection.
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28. ADVANTAGES OF LIPOSOME DRUG DELIVERY
 Soluble in both organic and aqueous media.
 Liposome’s are important for targeting drugs directly to the
liver, and brain. Lipsosomes easily crosses blood brain barrier.
EXAMPLE: Dopamine converted to L-Dopa.
 Used as a vehicles for vaccines.
DISADVANTAGES
 Less stable , easily susceptible to oxidation.
 Hence liposome’s are replaced by noisome an alternate for
liposome’s.
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29. Hydrogel based dds
Hydrogels are three dimensional networks of hydrophilic
polymers that are insoluble-
 Hydro gels are polymers which have the ability to swell in
water .
 Biodegradable hydro gels are used, due to its biocompatibility .
Examples: Hydroxymethylacrylate, used to minimize mechanical
irritation to surrounding tissue.
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30. EMULSION BASED DELIVERY
 Emulsions can be used for parenteral drug delivery of proteins
and peptides used to prolong the release of drug.
 e.g. subcutaneous administration of muramyl dipeptide in a
w/o emulsion. It is used to potentiate immune system.
CELLULAR CARRIERS
 Protein and peptides can be incorporated in erythrocytes to
achieve the prolong release or targeting.
 Resealed erythrocytes as delivery system for c-reactive protein,
and mainly used to target liver and spleen.
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31. PUMPS
Types of pumps:
1. IMPLANTABLE PUMPS
 Drug is implanted subcutaneously, and delivered by I.V
infusion.
 Pumps are filled with drug through a septum with a needle.
 Pumps deliver drugs to central vein for 7-14 days a constant rate.
2. MECHANICAL PUMPS
 Easily manipulated to deliver protein and peptide drugs.
Example: insulin has been successfully delivered by portable
syringe.
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32. NON PARENTERAL ROUTES OF ADMINISTRATION
Parenteral route is not properly achievable, hence other routes are
preferred.
 Oral route.
 Rectal route.
 Nasal route.
 Pulmonary route.
 Buccal route.
 Transdermal route.
 Ocular route
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33. ORAL ROUTE
 Encapsulated peptides or proteins in amino acids with
microsphere of approximately 10 micron in diameter , used for
oral delivery.
Example: Insulin and heparin.
 Orally administered insulin produces hypoglycemic effect .
DISADVANTAGES:
Acid catalyzed degradation in stomach.
 Proteolysis in GIT.
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34. Transdermal route of administration
 This is topical medication.
 Drug is absorbed through the skin.
EX: Insulin, vasopressin
ADVANTAGES:
 Controlled administration of drug is possible.
 Improved patient compliance.
 Drugs with short half lives can be administered.
DISADVANTAGES:
 High intra and inter patient variability.
 Low permeation because of high molecular weight.
 Hydrophilicity and lipophilicity of stratum corneum.
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35. Number of approaches are available for effective protein and peptide drug
delivery.
 They are
 IONTOPHORESIS
 PHONOPHORESIS
 PENETRATION ENHANCERS
 PRODRUG
 Iontophoresis: Used for local and systemic delivery of proteins and
peptides. In this an electric current is used to drive the molecules across
the skin surface.
Example: Transport of insulin using iontophoresis.
 Phonophoresis: The absorption is enhanced by thermal effect of
ultrasonic waves and subsequent alteration of physical structure of skin
surface.
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36. Pulmonary route of administration
 Lungs are attractive site for systemic delivery of proteins and
peptides because of their enormous surface area(70 sq.m)
 Alveoli and lungs are the absorption sites.
 Drugs are absorbed through lungs by simple diffusion, carrier
mediated transport
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37. ADVANTAGES:
 Decrease in dose requirement.
 Fast absorption
 Increased patient compliance
DISADVANTAGES:
 Inflammation may be observed in lungs.
 Degree of bioavailability was less due to hydrolytic enzymes
present in lungs
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38. Rectal route of administration
 Rectum is highly vascularised body cavity.
 Rectal mucosa is devoid of villi.
 Drugs are in form of suppositories, gel, dry powders.
EX: Insulin, calcitonin
ADVANTAGES:
 Reduced proteolytic degradation.
 Improved systemic bioavailability with co-administration of
absorption enhancers.
EX: surfactants
 Large dose can be administered.
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39. OCULAR ROUTE
 In this route enkephalins, thyrotrophin releasing hormones
,luteinizing hormones ,glucagon and insulin are administered
BUCCAL ROUTE
 Mucoadhesive dosage forms can be used for buccal route.
 Adsorption enhancers like salicylates or a surfactant is used for
protein and peptide delivery through buccal route.
Example:
 Oxytocin , vasopressin , insulin, are reported to be absorbed
through buccal mucosa . And adhesive gel, patches , tablets are
used.
 Insulin is absorbed through buccal mucosa in the presence of
sodium glycolate.
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40. The drugs are absorbed through oral mucosa mainly through the
non-keratinized regions.
ADVANTAGES:
 It can be attached or removed without any discomfort and pain.
 Well acceptability by patients.
 Drugs are absorbed rapidly.
DISADVANTAGES:
 Administration time is limited.
 Drug loss by accidental swallowing.
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41. Nasal route of administration
 The nasal route has been employed for producing local action on the
mucosa which is more permeable compared to oral mucosa.
 Nasal absorption is through passive diffusion.
EX: Insulin, human growth hormone.
ADVANTAGES:
 Rapid onset of action
 First pass metabolism can be avoided
 Better drug absorption
DISADVANTAGES:
 Long-term usage causes toxicity.
 Size of proteins and peptide drugs reduces systemic
bioavailability.
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42. PROTEIN FORMULATIONS
1
•Protein sequence modification (site
directed mutagenisis)
•PEGylation
2
•Proteinylation
•Microsphere encapsulation
3
•Formulating with permeabilizers
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43. PEGYLATION
 PEG is a non-toxic, hydrophilic, FDA approved, uncharged
polymer.
 Increases in vivo half life.
 Decreases immunogenicity.
 Increases protease resistance.
 Increases stability.
CH-CH-CH-CH-CH-CH-CH-CH-CH-CH
||||||||||
OHOHOHOHOHOHOHOHOHOH
+
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44. PROTEINYLATION
 Attachment of additional or secondary (non-immunogenic) proteins for in
vivo protection.
 Cross-linking with Serum Albumin.
 Increases in vivo half life.
 Cross-linking or connecting by protein engineering with antibody
fragments.
+
Protein
drug
scfc (antibody)
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45. FORMULATION WITH PERMEABILIZERS
 Salicylates (aspirin)
 Fatty acids
 Metal chelators (EDTA)
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46. Stability testing
 The capability of a particular formulation in a specific container/closure system to remain within
its physical,chemical,microbiological,toxicological and protective specifications.
 Evaluates the effect of environmental factors on the quality of the a drug substance or a
formulated product which is utilized for prediction of its shelf life, determine proper storage
conditions.
 General
 Selection of Batches
 Container Closure System
 Specification
 Testing Frequency
 Storage Conditions
 Stability Commitment
 Evaluation
 Statements/Labelling
 On-going Stability Studies
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47. Conclusion
 Protein and peptide based pharmaceuticals are rapidly becoming
a very important class of therapeutic agents and are likely to
replace many existing organic based pharmaceuticals in the very
near future.
 Peptide and protein drugs will be produced on a large scale by
biotechnology processes and will become commercially
available for therapeutic use.
 Their need in the clinical & therapeutic regions has intensified
the investigation for their convenient & effective delivery
through noninvasive system.
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48. References
 Controlled drug delivery concepts and advances by S.P vyas &
Roop k.khar Understanding the Fundamentals of Peptides and
Proteins
 By GARY HU (Bio processing journal -trends in development
in bio process technology)
 PEPTIDES AND PROTEINS IN PHARMACEUTICALS RA
TNAPARKHI M.P.,* CHAUDHARI S.P., PANDYA V.A. Intern
ational Journal of Current Pharmaceutical Research
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