This document discusses proteins and peptides, their structures and functions. It provides examples of proteins and peptides used for various purposes like erythropoietin for red blood cell production and insulin for maintaining blood sugar levels. It then discusses challenges with oral delivery of proteins and peptides like degradation in the gastrointestinal tract. Various approaches to overcome these challenges are described, such as modifying the peptide structure, adding lipid chains to increase permeability, and using enzyme inhibitors and absorption enhancers. Specific examples of formulations using these approaches are also provided.
Protein and peptide are biopolymers which yield more than two amino acids on hydrolysis.
Although the terms ‘proteins’ and ‘peptides’ are used freely, peptides are those with molecular weight below 10,000 and proteins are molecules with higher molecular weight.
Most therapeutic proteins and peptide-based drugs are administered by parenteral route and are incorporated in liposomes to prolong their action or fused with Immunoglobulins or Albumin to improve their half-life.
PEGylation is a proven technique for improving the potentials of Proteins/peptide delivery systems.
Protein and peptide are biopolymers which yield more than two amino acids on hydrolysis.
Although the terms ‘proteins’ and ‘peptides’ are used freely, peptides are those with molecular weight below 10,000 and proteins are molecules with higher molecular weight.
Most therapeutic proteins and peptide-based drugs are administered by parenteral route and are incorporated in liposomes to prolong their action or fused with Immunoglobulins or Albumin to improve their half-life.
PEGylation is a proven technique for improving the potentials of Proteins/peptide delivery systems.
proteins are chains of amino acids, each joined to it
neighbor by a specific type of covalent bond. The
polymerization of L-α-amino acids by peptide
bonds forms the structural framework of proteins. The
term protein is used for molecules composed of over 50
amino acids. The term peptide is used for molecules
composed of less than 50 amino acids.
The chemical and structural complexities involved
demand an effective delivery system in which the
physicochemical and biologic properties, including
molecular size, conformational stability, solubility,
sensitivity to light, moisture and heat, biological half-life,
immunogenicity, dose requirements, susceptibility to
break down in both physical and biological environments,
requirement for specialized mechanisms for transport
across biological membranes are to be considered.
Peptide and Protein Structure
It is essential to have an idea about structure of protein
and peptide in order to deal with various problems
encountered while developing drug delivery system.
The proteins are relatively large molecules with complex
structure. The peptide chains in peptides and proteins are
seldom linear and adapt a variety of specific folded three
dimensional patterns and conformations.
All peptides and proteins are polymers of amino acids
connected via amide linkages referred to as peptide
bonds.
• Primary structure: It denotes the number and
specific sequence of amino acids.
• Secondary structure: Arrangement of individual
amino acids along the polypeptide backbone.
• Tertiary structure: Three dimensional
arrangement of a single protein molecule.
• Quaternary structure: Proteins that contain two
or more polypeptide chains associated by noncovalent
forces
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
Protein and peptide drug delivery systemSagar 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.
Protein and peptide drug delivery system (PPDDS)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.
proteins are chains of amino acids, each joined to it
neighbor by a specific type of covalent bond. The
polymerization of L-α-amino acids by peptide
bonds forms the structural framework of proteins. The
term protein is used for molecules composed of over 50
amino acids. The term peptide is used for molecules
composed of less than 50 amino acids.
The chemical and structural complexities involved
demand an effective delivery system in which the
physicochemical and biologic properties, including
molecular size, conformational stability, solubility,
sensitivity to light, moisture and heat, biological half-life,
immunogenicity, dose requirements, susceptibility to
break down in both physical and biological environments,
requirement for specialized mechanisms for transport
across biological membranes are to be considered.
Peptide and Protein Structure
It is essential to have an idea about structure of protein
and peptide in order to deal with various problems
encountered while developing drug delivery system.
The proteins are relatively large molecules with complex
structure. The peptide chains in peptides and proteins are
seldom linear and adapt a variety of specific folded three
dimensional patterns and conformations.
All peptides and proteins are polymers of amino acids
connected via amide linkages referred to as peptide
bonds.
• Primary structure: It denotes the number and
specific sequence of amino acids.
• Secondary structure: Arrangement of individual
amino acids along the polypeptide backbone.
• Tertiary structure: Three dimensional
arrangement of a single protein molecule.
• Quaternary structure: Proteins that contain two
or more polypeptide chains associated by noncovalent
forces
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
Protein and peptide drug delivery systemSagar 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.
Protein and peptide drug delivery system (PPDDS)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 system to deliver the drug to the body to produced desired therapeutic action and activity against diseases and disorders is known as Drug delivery system
PROTEIN AND PEPTIDE DELIVERY THROUGH ORAL ROUTEAkhila Anil
DRUG DELIVERY SYSTEM (DDS) : M.PHARM
INTRODUCTION
FUNCTIONS OF PROTEINS AND PEPTIDES
MAIN BARRIERS OF EFFECTIVE ORAL DELIVERY
APPROACHES FOR ORAL DELIVERY OF DRUGS
PROTEINS: Proteins are the organic compounds made of amino acids and joined together by peptide bonds.
PEPTIDES: These are short polymers formed from the linking in a defined order of amino acids.
Protein and peptides are the most abundant material which act as hormones, transport protein, structural protein, receptor, immunoglobulin’s in living system and biological cell.
Protein and peptides are important part in several metabolic process, immunogenic defense and many other biological activities.
Protein and peptide use in the treatment of various diseases including Endocrine dysfunction, Infection diseases, Cancer, and CNS disorders.
According to their biological roles
Enzymes- Catalyses virtually all chemical reaction
Transport proteins i.e. Haemoglobin of erythrocytes
Defense proteins i.e. Immuno globulins Antibodies
Structural proteins i.e. Collagen in bones
Regulatory proteins i.e. insulin
Nutrient and storage proteins i.e. ovalbumin
According to their solubility
Globular proteins: Soluble in Water
Fibrous proteins: Insoluble in water
WHY PROTEN AND PEPTIDE DRUGS?
The protein and peptide are very important in biological cells.
Lack of proteins and peptides causes diseases like Diabetes mellitus.
Diabetes mellitus is cause due to the lack of protein called INSULIN.
Now a day R-DNA technology and hybridoma also use in protein and peptide based pharmaceuticals.
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.
Problems with proteins
Elimination by B and T cells.
Proteolysis by endo/exo peptidases.
Small proteins filtered out by the kidneys very quickly.
Unwanted allergic reactions may develop (even toxicity).
Loss due to insolubility/adsorption.
Formulation and evaluation of Muco adhesive Buccal Tablets of Ramprildoddaapurupa
The buccal mucosa lines the inner cheek and Buccal formulations are placed in the mouth between upper gingiva(gums) and cheek to treat local and systemic conditions.
Drugs which undergoes Extensive first pass metabolism and drug degradation in acidic media, GI tract can be administered through buccal route.
The oral cavity has been used as a site for local and systemic drug delivery.
How to Create Map Views in the Odoo 17 ERPCeline George
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Operation “Blue Star” is the only event in the history of Independent India where the state went into war with its own people. Even after about 40 years it is not clear if it was culmination of states anger over people of the region, a political game of power or start of dictatorial chapter in the democratic setup.
The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
Read| The latest issue of The Challenger is here! We are thrilled to announce that our school paper has qualified for the NATIONAL SCHOOLS PRESS CONFERENCE (NSPC) 2024. Thank you for your unwavering support and trust. Dive into the stories that made us stand out!
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
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Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
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Thesis Statement for students diagnonsed withADHD.ppt
Oral drug delivery proteins
1. 1
Presented by:-
Mr. Mane Avinash A.
M.Pharm sem.-ÍÍ
Dept. of Pharmaceutics
Guided by:-
Mr. Galgatte U.C.
Associate Professor
Dept. of Pharmaceutics
P. E. SOCIETY’S MODERN COLLEGE OF
PHARMACY NIGDI,PUNE,44
2015-16
2. Peptides are short polymers formed from the linking,
in a defined order, of α-amino acids. The link between
one amino acid residue and the next is known as an
amide bond or a peptide bond.
2
3. Proteins are large organic compounds made of amino
acids arranged in a linear chain and joined together by
peptide bonds between the carboxyl and amino groups
of adjacent amino acid residues
3
4. Primary structure- The amino acid sequence.
Secondary structure- Regularly repeating local structures
stabilized by hydrogen bond.
Tertiary structure- The three dimensional structure of the
polypeptide.
Quaternary structure-The structure formed by 2 or more
polypeptide chains associated by non covalent forces.
4
6. 1. Erythropoietin used for production of RBC.
2. Tissue plasminogen activator is used for Heart attack,
Stroke.
3. Oxytocin maintain labor pain.
4. Bradykinin increases the peripheral circulation.
5. Somatostatin decrease bleeding in gastric ulcer.
6. Gonadotropin induce ovulation.
7. Insulin maintain blood sugar level.
6
7. 1. Transport and storage of small molecules.
2. Coordinated motion via muscle contraction.
3. Mechanical support from fibrous protein.
4. Generation and transmission of nerve impulses.
5. Enzymatic catalysis.
6. Immune protection through antibodies.
7. Control of growth and differentiation via hormones.
7
8. 1. Elimination by B and T cells.
2. Proteolysis by endo/exo peptidases.
3. Small proteins filtered out by the kidneys very
quickly.
4. Unwanted allergic reactions may develop (even
toxicity).
5. Loss due to insolubility/adsorption.
8
9. Encapsulated peptides or proteins in amino acids with
microspheres of approximately 10 micron in diameter ,
used for oral delivery.
Example: Insulin and heparin.
Orally administered insulin produces hypoglycemic
effect .
9
10. The ease of administration and higher degree
of patient compliance with oral dosage forms
are the major reasons for preferring to deliver
proteins and peptides by mouth.
10
11. protection against the metabolic barrier in GIT
absence of a carrier system for absorption of peptides
with more than three amino acids
Proteins are labile due to susceptibility of the pepti
de backbone to proteolytic cleavage
Prodrug approach
olefenic substitution, d‐amino acid substitution,
dehydro amino acid substitution, carboxyl reduction
11
12. 1. Amino acid modifications
Metkephamid, an analog of methionine
encephalin with substitution of glycine₂ by l-alanine
and modified methionine, readily penetrated across
the nasal mucosa with 54% bioavailability relative
to subcutaneous administration but was orally
inactive
12
13. 2. Hydrophobization
Hydrophobization of peptides may be attempted by two
approaches. The first is peptide backbone modification
to include more of hydrophobic amino acids; the second
would be covalent conjugation of a hydrophobic
moiety—for example, a lipid or polymeric tail.
Increasing the hydrophobicity of a peptide or
protein by surface modification using lipophilic
moieties may be of particular benefit to trans
cellular passive or active absorption by
membrane penetration or attachment,
respectively; or it may simply aid in the increased
stability of the protein.
13
14. EXAMPLE
lipophilic modification of TRH by covalent
conjugation of lauric acid to this tripeptide
(Lau-TRH). The derivative was more stable in
rat plasma and was rapidly converted to TRH
in the intestinal mucosal homogenate.
14
15. Formulating for delivery through the
gastrointestinal (GI) tract requires a multitude
of strategies
To alter the environment for maximum
solubility and enzyme stability of protein by
using formulation excipients such as
buffers surfactants and protease inhibitors
To promote absorption through the
intestinal epithelium
15
17. Bonding of (PEG) and alkyl groups fatty acid
radicals to produce desired amphiphilic oligomers
oligomers are conjugated to proteins or peptides to
obtain desired amphiphilic products
can resist excessive degradation of protein or
peptide drugs
technology reduces self‐association, increases penetra
tion and increases compatibility with formulation i
ngredients than parent drug
17
19. Oral delivery is the most sought after route of
administration for most of the drugs and
pharmaceutical products, which depends on
the drug’s molecular structure or weight
Transport mechanism of macromolecules
19
21. (A) Transport mechanism of bio drug through
the intestinal epithelium membrane,
(B) Probable mechanism of penetration
enhancer,
C) enzyme inhibitors,
(D) Representative mechanism of prodrug
absorption and its activation.
21
23. Sr.
no
.
Approach Examples Effects on
bioavailability
Drawbacks
1 Absorption
enhancers
Bile salts,
fatty acids,
Surfactants
(anionic,
cationic)
Enhanced
bioavailability by
increased
membrane
permeation
Available transport
systems of both
proteins/peptides and
undesirable molecules in
GIT
2 Enzyme
inhibitors
Sodium
glycocholate
, camostate
mesilate
Resisted enzymes
degradation in
stomach and
intestines
Produced severe side
effects in the treatment of
chronic diseases such as
diabetes, etc.
3 Mucoadhesi
ve
polymeric
systems
Thiolated
polymer
Site–specific
delivery and
improved
membrane
permeation
Limitation due to the
mucus turnover in
absorption sites
(intestine)
4 Prodrug
strategies
Phenyl
propionic
acid
Prodrug
permeability
improved 1608fold
than parent drug
Lack of methodology,
structural
complexity, stability
problem of protein 23
24. Desmopressin acetate (DDAVP) is a synthetic
analogue of 8 arginine vasopressin: ant
diuretic hormone. Marketed by Aventis
pharmaceutical and is approved for diabetes
insipidus.0.16 % bioavailable
Novartis and Roche pharmaceutical market
cyclosporine (small lyophilic mol. For graft
rej.) 30% bioavailability
24
25. Aim:
Design and In Vitro Characterization of
Buccoadhesive Drug Delivery System of Insulin
Preparation Method:
A buccoadhesive drug delivery system of
Insulin was prepared by solvent casting
technique and characterized in vitro by surface
pH, bio adhesive strength, drug release and skin
permeation studies. Sodium carboxymethyl
cellulose-DVP was chosen as the controlled
release matrix polymer.
25
26. Result:
it is concluded that the system is a
success as compared to the conventional
formulations with respect to invasiveness,
requirement of trained persons for
administration and most importantly, the first
pass metabolism.
26
27. Company Product
name
Formulation Development
phase
Product
Apollo Life
Science
Oradell Tablet Clinical
phase I b
Insulin, TNF-
blocker
Emisphere Eligen Tablet Phase II Calcitonin,
insulin, PTH,
heparin
Nobex/Bioco
n
HIM2 Liquid Abandoned Insulin,
enkephalin,
calcitonin
27
28. Company Product name Formulation Development
phase
Product
Oramed ORMD-0801
ORMD-0901
Capsule Phase I Insulin/Exena
tide
Diasome
pharmaceutic
als
Hepatic-
directed
vesicles-
insulin
(HDV-1)
Tablet Phase II/III Insulin
Diabetology Capsulin Capsule Phase II Insulin
Merrion
pharma
(Ireland)
with Novo-
Nordisk
Vetsulin Matrix tablet Phase I Insulin and
GLP-1
analogues
Chiasma
(Israel)
Octreolin Suspension Phase I
(phase I
completed,
phase III
enrolling
Octreotide
28
29. NAME OF
PUBLICATIO
N
PUBLICATIO
N NO.
TYPE DATE INVENTOR
Oral delivery
of modified
transferrin
fusion
proteins
US8129504
B2
Grant 6 march
2012
Christopher
p.Prior ,
Homoyoun
sodeghi,And
rew turner.
Peptide
library and
screening
systems
US5432018
A
Grant Jul 11, 1995 William J.
Dower,
Steren
E.cwirla,
Ronald
W.barrett
Peptide
conjugate
US5442043 Grant Aug 15,1995 Takeda
chemical
industries
29
30. 1. McNally Ej. protein formulation and delivery. In: Drug and
the pharmaceutical sciences.2nd ed. New York: Marcel
Dekker; 2000.p.99-125
2. Novel drug delivery system by Dr. D. K. Jain and Dr. D. T.
Baviskar Nirali prakashan Page no.14.1-14.7
3. Agarwal, V., Khan, M.A., 2001. Current status of the oral
delivery of insulin. Pharm. Tech. 25 (10), 76–90.
4. Antunes, F., Andrade, F., Ferreira, D., Morck, N.H.,
Sarmento, B., 2013. Models to predict intestinal
absorption of therapeutic peptides and proteins. Curr.
Drug Metab. 14 (1), 4–20.
5. Aoki, Y., Morishita, M., Asai, K., Akikusa, B., Hosoda, S.,
Takayama, K., 2005. Region dependent role of the
mucous/ glycocalyx layers in insulin permeation across
rat small intestinal membrane. Pharm. Res. 22 (11),
1854–1862.
30