DRUG DELIVERY SYSTEM M. PHARM PHARMACEUTICS
PROTEIN AND PEPTIDE
DRUG DELIVERY
SUBMITTED BY: RAHUL PAL
M. PHARM
SUBMITTED TO: MR. GULSHAN
RATHORE
DEPARTMENT OF

PROTEIN & PEPTIDE
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

 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
FUNCTIONS OF
PROTEINS

1) Erythropoietin used for production of RBC.
2) Tissue plasminogen activator is used for Heart attack, Stroke.
3) Oxytocin maintain labor pain (caused by contractions of the muscles of
the uterus and by pressure on the cervix).
4) Bradykinin increases the peripheral circulation.
5) Somatostatin decrease bleeding in gastric ulcer.
6) Gonadotropin induce ovulation.
7) Insulin maintain blood sugar level.
IMPORTANCE OF
PROTEINS

• Enzymatic Barrier: Limits absorption of protein drugs from G.I. tract.
• Intestinal Epithelial Barrier involved in the transport of protein drugs
across the intestinal epithelium.
 Capillary Endothelial Barrier involved in transport of protein drugs
across the capillary endothelium.
 Blood Brain Barrier (BBB).
BARRIERS TO
PROTEIN DRUG
DELIVRY

The oral delivery of therapeutic proteins and peptides can be successfully,
Achieved by using various carrier systems like:
 Dry Emulsions (Dry emulsions are prepared by drying liquid o/w emulsions
containing a solid carrier in the aqueous phase)
 Cellular Carriers (e.g.: Resealed erythrocytes)
 Microspheres, Liposome, Nanoparticles.
 Hydrogels (drugs enclosed in gelling polymers)
FORMULATION OF
DELIVERY SYSTEM

There are of four types of protein:
1. Primary Protein- The amino acid sequence.
2. Secondary Protein: Regularly repeating local structures stabilized by
hydrogen bond.
3. Tertiary Protein: Three dimensional (3D) structure of polypeptide.
4. Quaternary Protein: The structure formed by several protein molecules
(polypeptide chain).
STRUCTURE OF
PROTEIN

DIFFERENT PROTEIN STRUCTURES

Why we need Protein and Peptide Drug?
• The protein and peptide are very important in biological cells.
• Lack of protein and peptide causes disease like Diabetes Mellites (DM).
• Diabetes Mellitus (DM) is caused by the lack if protein called Insulin.
• Now a days R-DNA technology and hybridoma technique also used in
protein and peptide based pharmaceuticals.

• Stability Testing: The capability of a particular formulations in a specific
container/closure system to remain within its physical, chemical,
microbiological, toxicological and protective specification.
• Evaluate the effect of environmental factors on the quality of the drug
substance or a formulated product which is utilized for prediction or its shelf
life and proper storage condition.
EVALUATION OF PROTEIN AND
PEPTIDE DELIVERY

Due to complexity of protein, bioassay are required to asses potency of the
formulation. Bioassay are two types: in vitro and in vivo.
• In case of in vitro bioassay response of cells to hormones and growth factors
is monitored. In case of in vivo bioassay pharmacological response of
animals to protein s monitored.
• E.g. Post injection BSL in rabbits is measured for bioassay of insulin.
BIOASSAY

• Protein containing aromatic amino acid residues such as phenyl alanine,
tyrosine, tryptophan can be detected by UV Spectroscopy. It can be used as
an analytical determination methods.
• In the presence of protein in an acidic medium, absorption maximum of
Coomassie brilliant blue G-250 dye changes. Lastly the determination of
concentration of the protein in the sample.
UV Spectroscopy
Bradford Assay

DSC used as a tool for investigating transition of conformation as a function
of temperature and more important, the effect of potential stabilizing
excipients in a protein solution.
Used to study stability of protein and peptide. Various modes used are:
i. Normal Phase HPLC
ii. Reverse Phase HPLC
iii. Ion exchange
iv. Chromatofocusing.
Chromatography
Differential Scanning Calorimetry
Electrophoresis

Smart Polymer based delivery system: Biodegradable polymeric systems delivering
protein and peptide drugs. Smart polymer-based injectable drug delivery systems.
Smart polymer are classified according to the external stimulus they respond to:
01. Temperature Sensitive: Poly (ethylene oxide)-poly (propylene oxide).
02. pH Sensitive Polymer: Poly (methacrylic acid).
03. Photo-Sensitive Polymer: Polyvinyl alcohol.
04. Phase Sensitive Polymers: Poly (D,L –Lactide)
RECENT ADVANCE

• Leupron: (Drug - Leuprolide : Used for Prostatic cancer)
• Pergonal: (FSH & LH: Used in cases of female infertility)
• Calcimar: (Salmon Calcitonin: Used to treat Hypercalcemia)
• Acthar: (Corticotrophin: Used in cases of Hormone deficiency)
Certain Marketed
Formulations