Protein and Peptide drug delivery system are the Novel drug Delivery System. Proteins and peptides are the most abundant components of biological cells. They exist functioning such as enzymes, hormones, structural element and immunoglobulin. The distinction between peptides and proteins is having a peptide contains less than 20 amino acids, having a molecular weight less, while a protein possesses 50 or more amino acids and its molecular weight lies above this value. The most of pharmaceutical proteins and peptides are absorbed IM, IV and Subcutaneous route of Absorption, but the oral route is more convenient for absorption of protein as compared to other. Various problems associated with administration of protein and peptide drugs are needed to overcome by different pharmaceutical approaches. Several approaches available for maximizing pharmacokinetic and pharmacodynamics properties are chemical modification, formulation vehicles, mucoadhesive polymeric system, use of enzyme inhibitors, absorption enhancers, penetration enhancers etc.

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PROTEIN AND PEPTIDE DRUG DELIVERY SYSTEM
Mr. Sagar Kishor Savale
[M.pharm First Year Student (sem - II)]
[Department of Pharmaceutics]
[R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, 425405, Dist.
Dhule, Maharashtra, India]
avengersagar16@gmail.com
Date: 9 March. 2016 Roll No.: PH 16

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CONTENT
Sr.No. TITLE Slide No.
1 ABSTRACT AND KEYWORDS 4
2 INTRODUCTION 5 - 7
3 STRUCTURE OF PROTEIN 8
4 CLASSIFICATION OF PROTEIN 9
5 NEED OF PROTEIN AND PEPTIDE DRUG DELIVERY SYSTEM 10
6 ADVANTAGES OF PROTEIN AND PEPTIDE DRUG DELIVERY
SYSTEM
11
7 FUNCTIONS OF PROTEIN AND PEPTIDE DRUG DELIVERY
SYSTEM
12
8 ROUTES OF ABSORPTION 13 - 16
9 PHARMACEUTICAL APPROACH 17 - 22
Department of Pharmaceutics | Sagar Savale

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Sr.No. TITLE Slide No.
10 STABILITY ASPECTS 23
11 APPLICATIONS 24 - 25
12 RECENT ADVANCES 26
13 MARKETED FORMULATIONS 27
14 CONCLUSION 28
15 REFERENCES 29
Department of Pharmaceutics | Sagar Savale
CONTENT

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ABSTRACT
Department of Pharmaceutics | Sagar Savale
Protein and Peptide drug delivery system are the Novel drug Delivery System. Proteins and
peptides are the most abundant components of biological cells. They exist functioning such as
enzymes, hormones, structural element and immunoglobulin. The distinction between peptides
and proteins is having a peptide contains less than 20 amino acids, having a molecular weight
less, while a protein possesses 50 or more amino acids and its molecular weight lies above this
value. The most of pharmaceutical proteins and peptides are absorbed IM, IV and Subcutaneous
route of Absorption, but the oral route is more convenient for absorption of protein as compared
to other. Various problems associated with administration of protein and peptide drugs are needed
to overcome by different pharmaceutical approaches. Several approaches available for
maximizing pharmacokinetic and pharmacodynamics properties are chemical modification,
formulation vehicles, mucoadhesive polymeric system, use of enzyme inhibitors, absorption
enhancers, penetration enhancers etc.
Keywords: Protein, Peptide, Pharmaceutical approaches, Novel Drug Delivery System,
Hormone, Enzymes.

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 Proteins is a basic constituent of the Cytoplasm of the cell.
 The term “Protein” is derived from a Greek word Proteios - means holding the first place.
 The high molecular weight compound containing a Nitrogen rich most abundant substances
present in animals and plants system.
 Proteins are the linear chains of amino acids that are held together by covalent linkages called
“ Peptide bonds”.
 The term protein is used for molecules composed of over 50 amino acids, and peptide for
molecules composed of less than 50 amino acids.
 Protein is play major part in Transport of Oxygen and Carbon dioxide by Hemoglobin Present
in Red blood cells.
 Protein is Participate in Blood Clotting.
Department of Pharmaceutics | Sagar Savale

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ENDOGENOUS PROTEINS AND PEPTIDES
These plays an important role in the regulation and integration of life processes.
e.g.
 Hemoglobin, myoglobin, etc. affect the transport of oxygen within the body.
 Enzymes, hormones and antibodies, etc. catalyze, regulate and protect the body chemistry.
Department of Pharmaceutics | Sagar Savale

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PROTEIN AND PEPTIDE DRUG DELIVERY SYSTEM
DEFINITION
 Protein - Protein can be define as high molecular weight mixed polymer of α-amino acid
Joined together with peptide linkage is known as protein.
 Protein is a group of amino acid (Essential amino acid and Non Essential amino acid).
 Peptide - Peptides are short polymers of amino acid (monomers) linked by peptide
bonds is known as peptide.
 The covalent chemical bonds formed between two molecules when the carboxyl group of
one molecule reacts with the amino group of the other molecule.
Department of Pharmaceutics | Sagar Savale

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STRUCTURE OF PROTEIN
The structure of protein divided in to four types:
Quaternary
Structure
Tertiary
Structure
Secondary
Structure
Primary
Structure
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CLASSIFICATION OF PROTEIN
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On the basis of Structure

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NEED
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Department of Pharmaceutics | Sagar Savale
ADVANTAGES
Erythropoietin used for production of RBC
Tissue plasminogen activator - Heart attack, Stroke
Oxytocin is used in management of labor pain
Bradykinin increases the peripheral circulation
Insulin maintain blood sugar level

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Transportation
Mechanical support
Generation and transmission of nerve impulses
Enzymatic catalysis
Immune protection
Regulation
Body Building and Structure Formation
FUNCTIONS

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ROUTES OF ABSORPTION
Most pharmaceutical proteins and peptides are formulated as solution or suspensions and
delivered by invasive route such as IM, IV, or SC Injections.
These routes have their own Demerits like -
 Poor patient compliance.
 Pain and discomfort associated with these routes.
 Inconvenience to treat the pediatric patients.

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Department of Pharmaceutics | Sagar Savale
The oral route presents a series of advantages towards other drug delivery
systems like
 It is most convenient route of drug administration.
 Avoidance of pain and discomfort associated with injections.
 Higher patient compliance.

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CHALLENGES IN ORAL ROUTE OF ADMINISTRATION
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However still designing oral protein and peptide drug delivery have poses a persistent challenge
to the formulation scientists because of their several unfavorable physicochemical properties like
 Large molecular size.
 Susceptibility to enzymatic degradation.
 Short plasma half-life.
 High immunogenicity.
 Tendency to undergo denaturation.
 Less bioavailability (less than 1%).
 The other routes that have been tried with varying degrees of success are : Oral, Buccal,
Intranasal, Pulmonary, Transdermal and Ocular.

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POTENTIAL PROBLEMS IN ORALABSORPTION
The oral administration of protein and peptide drugs faces two potential problems during their
oral absorption :
1. Metabolic degradation of therapeutic proteins and peptides by variety of proteolytic enzymes.
2. Poor membrane permeability.
Department of Pharmaceutics | Sagar Savale

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8. PHARMACEUTICAL APPROACHES
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 Chemical Modification (Prodrug approach) - 1. Amino acid modification 2. Hydro
phobization.
 Enzyme (protease) inhibitors.
 Penetration enhancers.
 Formulation vehicles.
 Mucoadhesive polymeric systems.

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Department of Pharmaceutics | Sagar Savale
CHEMICAL MODIFICATION
 A chemical modification of protein and peptide drugs improves their enzymatic stability and
membrane permeation. Also it can be used for minimizing the immunogenicity.
 Prodrug approach includes
 Amino acid modification - Modification of individual amino acids by the substitution of D-
amino acid with the L-amino acid can significantly alter physiological properties of proteins
and peptides. e.g. Desmopressin and Deaminovasopressin.
 Hydrophobization - The Surface modification using the lipophilic moieties.
e.g. NOBEX INSULIN.

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Department of Pharmaceutics | Sagar Savale
ENZYME (PROTEASE) INHIBITORS
 The whole GIT and liver tend to metabolize proteins and peptides into smaller
fragments of 2-10 amino acids with the help of variety of proteolytic enzymes.
 So protease inhibitors are co-administered with proteins and peptides to alter the
environment for maximum enzyme stability to supress proteolytic activity.
 They are of 4 major types
1. Aspartic proteases [Pepsin]
2. Cystinyl proteases [Papain]
3. Serinyl proteases [Thrombin]
4. Metallo proteases [Carboxypeptidase]

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Department of Pharmaceutics | Sagar Savale
PENETRATION ENHANCERS
 Penetration enhancers are the formulation components that is important to disrupt
the mucosal barrier to improve the permeation of large macromolecular substances
like proteins and peptides.
 Following classes of compounds are commonly used :
1. Surfactants - Polysorbate, SLS
2. Chelating agents - EDTA.
3. Fatty acids - Sodium caprate.
4. Mucoadhesive polymers - Thiomers, cellulose derivatives.
5. Phospholipids - PC.

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Department of Pharmaceutics | Sagar Savale
FORMULATION VEHICLES
The oral delivery of therapeutic proteins and peptides can be successfully
achieved by using various carrier systems like:
 Dry emulsions
 Microspheres
 Liposomes
 Nanoparticles

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MUCOADHESIVE POLYMERIC SYSTEMS
Department of Pharmaceutics | Sagar Savale
 These systems prevent the Presystemic metabolism of the therapeutic proteins and
peptides.
 e.g. Thiomers, polyacrylic acid derivatives and cellulose derivatives.

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Department of Pharmaceutics | Sagar Savale
STABILITY ASPECTS
Two basic mechanisms
1. Physical
2. Chemical
In chemical degradation, the native structure of the protein is changed
by modifications into the primary structure.
In physical degradation, the native structure of the protein is changed
by modifications into the higher order structures of proteins i.e.
secondary, tertiary or quaternary structure.

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APPLICATIONS
Department of Pharmaceutics | Sagar Savale
Protein/peptide
drugs
Biomedical
applications
CVS active
Angiotensin 2 antagonist
Bradykinin
Captopril
Lowering blood pressure
Improving peripheral
circulation
Heart failure management
CNS active
Cholecystokinin
Β-endorphin
Suppressing appetite
Relieving pain

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APPLICATIONS
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GI active
Gastrin antagonist
Pancreatic enzymes
Reducing secretion of gastric
acid
Digestive supplement
Immunomodulation
Bursin
Cyclosporin
Interferon
Selective B-cell differentiating
harmone
Inhibits functions of T-
lymphocyte
Enhancing activity of killer
cells
Metabolism modulating
Insulin
Vasopressin
Treating diabetes mellitus
Treating diabetes insipidus

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Department of Pharmaceutics | Sagar Savale
RECENT ADVANCES
1. PEGylation
2. Depo-Foam TECHNOLOGY

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Department of Pharmaceutics | Sagar Savale
MARKETED FORMULATIONS
Product Formulation Route Indication
Pergonal FSH and LH i.m. infertility
Lupron Leuprolide i.m. Prostatic cancer
Calcimar Salmon calcitonin s.c. hypercalcemia
Glucagon Glucagon i.m. i.v. s.c. Hypoglycemia
Acthar Corticotropin i.m. i.v. s.c. Hormone
Deficiency

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Department of Pharmaceutics | Sagar Savale
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.
 Systemic delivery of protein and peptides is extremely challenging.
 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 for their convenient & effective drug delivery
system.

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Department of Pharmaceutics | Sagar Savale
REFERENCES
 Smith EL, Hill RL, Lehman IR, Lefkowitz RJ, Handler P, White A, Principles of biochemistry: General
aspects, 7th Ed., McGraw-Hill, New York, 1983.
 Bummer PM, Koppenol S, Chemical and physical considerations in protein and peptide stability; In:
Protein Formulation and Delivery, Drugs and the Pharmaceutical Sciences, McNally EJ, Marcel Dekker,
New York, 2000, 15-18.
 N.K. Jain; Advances In Controlled And Novel Drug Delivery; Ist Edition-2001; CBS Publishers and
Distributors; 232-260.
 U. Satyanarayana, U. Chakrapani; Biochemistry ; Third Edition -2006; Uppala Authors And Publishers
Interlinks ; 43-68.
 Clark AR, Shire SJ, Protein formulation and delivery, In: McNally EJ, editors, Drugs and the
Pharmaceutical Science, Marcel Dekker, New York, 99, 2000, 201-212.
 Degum IT, Celebi N, Controlled delivery of peptides and proteins, Curr Pharm Des 13, 2007, 99-117.
 Roberts MJ, Bentley MD, Harris JM, Chemistry for peptide and protein PEGylation. Adv Drug Del Rev
54, 2002, 459-76.
 E. J. Mcnally ; Protein Formulation and Delivery ; Marcel-dekker (P) ; Vol.99 ; 1-4 , 71-110, 239-243.
 West JL, Hubbell JA, Localized intravascular protein delivery from photopolymerized hydrogels, Proc Int
Symp Control Rel Bioact Mater, 22, 1995, 17-18.
 Adessi C, Sotto C, Converting a peptide into a drug: Strategies to improve stability and bioavailability,
Curr Med Chem, 9, 2002, 963-978.

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Department of Pharmaceutics | Sagar Savale
Have a good day……………….