Protein and peptide drug delivery system

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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]

[email protected]

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

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7 FUNCTIONS OF PROTEIN AND PEPTIDE DRUG DELIVERY

SYSTEM

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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


CONTENT

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ABSTRACT


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.


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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.


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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 acidJoined 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.


videos/What is a Protein- Learn about the 3D shape and function of macromolecules(0).mp4

videos/What Is Peptide-.mp4

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STRUCTURE OF PROTEIN

The structure of protein divided in to four types:

Quaternary

StructureTertiary

StructureSecondary

Structure

Primary

Structure


videos/Protein Structure - University Of Surrey(0).mp4

videos/structure of protein.JPG

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CLASSIFICATION OF PROTEIN


On the basis of Structure

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NEED


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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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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


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 ORAL ABSORPTION

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.


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8. PHARMACEUTICAL APPROACHES


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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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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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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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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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


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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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


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


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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RECENT ADVANCES

1. PEGylation

2. Depo-Foam TECHNOLOGY

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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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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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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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Have a good day……………….

Protein and peptide drug delivery system

Health & Medicine

Transcript of Protein and peptide drug delivery system