Barriers to Protein and peptide drug delivery system JaskiranKaur72
Protein and peptide DDS are novel systems of drug delivery.
The successful delivery of peptide and protein-based pharmaceuticals is primarily determined by its ability to cross the various barriers presented to it in the biological milieu. Various barriers encountered are-
1 Physiological Barrier
2 Intestinal Epithelial barriers
3 Capillary Endothelial Barrier
4 Blood-Brain barrier (BBB)
pH-activated and Enzyme-activated drug delivery systemSakshiSharma250807
As per the syllabus of M.Pharma (1st sem.) I have presented the topic pH-activated and Enzyme-activated. This comes under rate-controlled drug delivery system under the subject Drug delivery system. Best wishes from Sakshi Sharma
Barriers to Protein and peptide drug delivery system JaskiranKaur72
Protein and peptide DDS are novel systems of drug delivery.
The successful delivery of peptide and protein-based pharmaceuticals is primarily determined by its ability to cross the various barriers presented to it in the biological milieu. Various barriers encountered are-
1 Physiological Barrier
2 Intestinal Epithelial barriers
3 Capillary Endothelial Barrier
4 Blood-Brain barrier (BBB)
pH-activated and Enzyme-activated drug delivery systemSakshiSharma250807
As per the syllabus of M.Pharma (1st sem.) I have presented the topic pH-activated and Enzyme-activated. This comes under rate-controlled drug delivery system under the subject Drug delivery system. Best wishes from Sakshi Sharma
formulation and evaluation of delivery system of protein and peptide.pptxKishor Singha
the presention gives idea about various formulation and evaluation of various delivery system based on the delivery routes for protein and peptide drug delivery in the body.
This presentation includes the detail information about the physics of tablet compression and compaction, Compression, Effect of friction, distribution of forces, compaction profiles,solubility.
Niosomes, Aquasomes, Phytosomes,Electrosomes Molecular pharmaceutics (MPH 201T) PRESENTATION BY- NARAYAN R KOTE M PHARM [PHARMACEUTICS] ROLL NO. 8 GUIDANCE BY :- Dr . TIWARI S. S
CONTENTS
NIOSOMES
AQUASOMES
PHYTOSOMES
ELECTROSOMES
NIOSOMES
Niosomes are a novel drug delivery system, in which the medication is encapsulated in a vesicle. The vesicle is composed of a bilayer of non-ionic surface active agents and hence the name niosomes.
The niosomes are very small, and microscopic in size.
Their size lies in the nanometric scale. Although structurally similar to liposomes, they offer several advantages over them.
Niosomes have recently been shown to greatly increase transdermal drug delivery and also can be used in targeted drug delivery, and thus increased study in these structures can provide new methods for drug delivery.
STRUCTURE OF NIOSOMES
Structurally, niosomes are similar to liposomes, in that they are also made up of a bilayer.
However, the bilayer in the case of niosomes is made up of non-ionic surface active agents rather than phospholipids as seen in the case of liposomes.
Most surface active agents when immersed in water yield micellar structures however some surfactants can yield bilayer vesicles which are niosomes.
STRUCTURE OF NIOSOMES
Structurally, niosomes are similar to liposomes, in that they are also made up of a bilayer.
However, the bilayer in the case of niosomes is made up of non-ionic surface active agents rather than phospholipids as seen in the case of liposomes.
Most surface active agents when immersed in water yield micellar structures however some surfactants can yield bilayer vesicles which are niosomes.
APPLICATION OF NIOSOMES
Drug Targetting
One of the most useful aspects of niosomes is their ability to target drugs.
Niosomes can be used to target drugs to the reticuloendothelial system.It can be achieved by coating with polymer e.g. PEG.
In Diagnosis
Niosomes have also been used as carriers for iobitridol, a diagnostic agent used for X-ray imaging.
Anti-neoplastic Treatment
Most antineoplastic drugs cause severe side effects.
Niosomes can alter the metabolism; prolong circulation and half life of the drug, thus decreasing the side effects of the drugs.
Niosomes, is decreased rate of proliferation of tumor and higher plasma levels accompanied by slower elimination.Leishmaniasis :-
Leishmaniasis is a disease in which a parasite of the genus Leishmania invades the cells of the liver and spleen.
Use of niosomes in tests conducted showed that it was possible to administer higher levels of the drug without the triggering of the side effects, and thus allowed greater efficacy in treatment.
Delivery of Peptide Drugs:-
Oral peptide drug delivery has long been faced with a challenge of bypassing the enzymes which would breakdown the peptide.
Use of niosomes to successfully protect the peptides from gastrointestinal peptide breakdown is being investigated.
In an in-vitro study conducted by ODDS.
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.
formulation and evaluation of delivery system of protein and peptide.pptxKishor Singha
the presention gives idea about various formulation and evaluation of various delivery system based on the delivery routes for protein and peptide drug delivery in the body.
This presentation includes the detail information about the physics of tablet compression and compaction, Compression, Effect of friction, distribution of forces, compaction profiles,solubility.
Niosomes, Aquasomes, Phytosomes,Electrosomes Molecular pharmaceutics (MPH 201T) PRESENTATION BY- NARAYAN R KOTE M PHARM [PHARMACEUTICS] ROLL NO. 8 GUIDANCE BY :- Dr . TIWARI S. S
CONTENTS
NIOSOMES
AQUASOMES
PHYTOSOMES
ELECTROSOMES
NIOSOMES
Niosomes are a novel drug delivery system, in which the medication is encapsulated in a vesicle. The vesicle is composed of a bilayer of non-ionic surface active agents and hence the name niosomes.
The niosomes are very small, and microscopic in size.
Their size lies in the nanometric scale. Although structurally similar to liposomes, they offer several advantages over them.
Niosomes have recently been shown to greatly increase transdermal drug delivery and also can be used in targeted drug delivery, and thus increased study in these structures can provide new methods for drug delivery.
STRUCTURE OF NIOSOMES
Structurally, niosomes are similar to liposomes, in that they are also made up of a bilayer.
However, the bilayer in the case of niosomes is made up of non-ionic surface active agents rather than phospholipids as seen in the case of liposomes.
Most surface active agents when immersed in water yield micellar structures however some surfactants can yield bilayer vesicles which are niosomes.
STRUCTURE OF NIOSOMES
Structurally, niosomes are similar to liposomes, in that they are also made up of a bilayer.
However, the bilayer in the case of niosomes is made up of non-ionic surface active agents rather than phospholipids as seen in the case of liposomes.
Most surface active agents when immersed in water yield micellar structures however some surfactants can yield bilayer vesicles which are niosomes.
APPLICATION OF NIOSOMES
Drug Targetting
One of the most useful aspects of niosomes is their ability to target drugs.
Niosomes can be used to target drugs to the reticuloendothelial system.It can be achieved by coating with polymer e.g. PEG.
In Diagnosis
Niosomes have also been used as carriers for iobitridol, a diagnostic agent used for X-ray imaging.
Anti-neoplastic Treatment
Most antineoplastic drugs cause severe side effects.
Niosomes can alter the metabolism; prolong circulation and half life of the drug, thus decreasing the side effects of the drugs.
Niosomes, is decreased rate of proliferation of tumor and higher plasma levels accompanied by slower elimination.Leishmaniasis :-
Leishmaniasis is a disease in which a parasite of the genus Leishmania invades the cells of the liver and spleen.
Use of niosomes in tests conducted showed that it was possible to administer higher levels of the drug without the triggering of the side effects, and thus allowed greater efficacy in treatment.
Delivery of Peptide Drugs:-
Oral peptide drug delivery has long been faced with a challenge of bypassing the enzymes which would breakdown the peptide.
Use of niosomes to successfully protect the peptides from gastrointestinal peptide breakdown is being investigated.
In an in-vitro study conducted by ODDS.
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 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
Pharmacokinetics and pharmacodynamics of Biotechnological drugs-SnehalTidke
Pharmacokinetics and pharmacodynamics of biotechnological drugs along with appliations- Proteins and peptides, monoclonal antibodies, oligonucleotides, gene therapy and vaccines
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.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
2. POINTS TO BE CONSIDERED...
• Definition of proteins.
• Classification of proteins.
• Properties of proteins.
• Various routes of administration of proteins and peptides.
• Development of delivery system for peptide based
pharmaceuticals.
• Barriers to protein drug delivery.
3. PROTEINS
Proteins are biochemical compounds consisting of one or
more polypeptides, which is a single linear polymer chain
of amino acids bonded together by peptide bonds between
the carboxyl and amino groups of adjacent amino acid
residues. Like other biological macromolecules, proteins are
essential parts of organisms and participate in virtually
every process within cells, making them ideal for various
testing procedures to identify effective disease prevention
techniques.
4. EXAMPLES OF PROTEINS,
Casein from milk, collagen , keratin, polymerase,actin ,
myosin,haemoglobin,antibodies,insulin, snakevenom.
CLASSIFICATION OF PROTEINS
Proteins can be classified:
1. On the basis of structure.
2. On the basis of functions.
5. 1.ON THE BASIS OF STRUCTURE...
• PRIMARY STRUCTURE:
Protein primary structure is the linear sequence of amino acids
in a peptide or protein.
Amino acid, eg- glycine, alanine.
Peptide bonds,covalently
attached.
6. • SECONDARY STRUCTURE:
Protein secondary structure is
the three dimensional form of
local segments of proteins.
The two most common
secondary structural elements
are alpha helics and beta
sheets, though beta turns and
omega loops occur as well.
7. • TERTIARY STRUCTURE:
Protein tertiary structure is the three
dimensional shape of a protein. The
tertiary structure will have a single
polypeptide chain "backbone" with
one or more protein secondary
structures, the protein domains.
Amino acid side chains may interact
and bond in a number of ways. The
interactions and bonds of side chains
within a particular protein determine
its tertiary structure.
8. • QUATERNARY STRUCTURE:
Protein quaternary structure is
the number and arrangement
of multiple folded protein
subunits in a multi-subunit
complex. The quaternary
structure refers to the number
and arrangement of the protein
subunits with respect to one
another. Examples of proteins
with quaternary structure include
hemoglobin, DNA polymerase,
and ion channels.
9. 2. ON THE BASIS OF FUNCTIONS...
• ENZYMES: For example, DNA polymerases are enzymes that
synthesize DNA molecules from deoxyribonucleotides, the
building blocks of DNA. These enzymes are essential for DNA
replication and usually work in pairs to create two identical DNA
strands from a single original DNA molecule. During this process,
DNA polymerase "reads" the existing DNA strands to create two
new strands that match the existing ones.
• HORMONES: Examples of peptide hormones include
antidiuretic hormone (ADH), a pituitary hormone important in
fluid balance, and atrial-natriuretic peptide, which is produced
by the heart and helps to decrease blood pressure.
10. • ANTIBODIES:An antibody (Ab), also known as an
immunoglobulin (Ig), is a large, Y-shaped protein
produced mainly by plasma cells that is used by the
immune system to neutralize pathogens such as
pathogenic bacteria and viruses.
• MOTOR PROTEINS: Motor proteins are class of
molecular motors that are able to move along the surface
of a suitable substrate. They convert chemical energy
into mechanical work by the hydrolysis of ATP.
Flagellar rotation, however, is powered by proton pump.
For example, actin and myosin,present in muscle fibers
in animals.
11. PROPERTIES OF PROTEINS
Solubility and partition coefficient: Aqueous
solubility of peptide is strongly dependent upon pH,
presence of metallic ion, ionic strength and
temperature. At isoelectric point the aqueous solubility of
peptide is minimal where the drug is neutral or has no net
charge. Peptides are very hydrophilic with a very low
octanol-water partition coefficient, so to improve the
absorption of peptides by passive diffusion, their lipophilicity
should be increased.
12. Aggregation, self association and hydrogen
bonding: Self-aggregation tendency of peptides modifies
their intrinsic properties. Human insulin was found to be
more self-aggregating than bovine insulin. Additions of
additive like non ionic surfactants (Pluronic F 68) stabilize
the peptide formulation against self aggregation.
13. Various routes of administration of proteins and
peptides.
1. Parenteral systemic delivery
2. Non-parenteral systemic delivery
a) Oral route
b) Nasal route
c) Buccal route
d) Ocular route
e) Rectal route
f) Transdermal route
14. 1. PARENTRAL SYSTEMIC DELIVERY-
Parenteral delivery consist of three major routes, IV,IM and SC.
Intravenous administration is currently the method of choice for systemic
delivery of proteins and peptides eg. erythropoietin injection. Insulin,
interferons, and gammaglobulins have been reportedly metabolized
and/or bound to tissue at injection sites following IM administration, and
as a result, the systemic bioavailability of these protein drugs following IM
administration is often less than that obtained by IV injection. For SC
administration, insulin is best example for the treatment of
diabetes,The controlled delivery of peptide or protein based
pharmaceutical from subcutaneously implanted polymeric devices in
which gel formulation of cross linked
polyacrylamide‐polyvinylpyrrolidone is used to achieve the prolonged
release of immunoglobulin, luteinizing hormone, bovine serum albumin,
insulin, and prostaglandin.
15. 2. Non-parentral systemic delivery-
a)Oral route: 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. Strategies for oral delivery:
• Alter the GIT environment for maximum solubility and enzyme
stability of the protein by using formulation excipients such as
buffers, surfactants and protease inhibitors.
• If the enzyme attack can be defeated or delayed, the proteins can
be presented for absorption.Proteins and peptides could be
derivatised with polyethylene glycol (PEG) to achieve properties
such as retention of activity, prevention of immunogenicity and
prevention of excessive enzymatic degradation.
16. • Another strategy for oral delivery is to promote absorption
through the intestinal epithelium.A typical transport mechanism
for proteins across the epithelial boundary is paracellular
transport. There are tight junctions between each of the cells in
the epithelium that prevent water and aqueous soluble
compounds from moving past these cells.A number of absorption
enhancers are available that will cause these tight junctions to
open transiently, allowing water‐soluble proteins to pass. Fatty
acids, surface‐active agents, EDTA, glycerides and bile salts
have all been shown to be effective in opening these tight
junctions.
17. Potential problem associated with oral protein
delivery:
The oral administration of peptide and protein drugs faces two
problems.
• The first is protection against the metabolic barrier in GIT. The
whole GIT and liver tend to metabolize proteins and peptides into
smaller fragments of 2-10 amino acids with the help of a variety
of proteolytic enzyme (proteases).
• The second problem is the absence of a carrier system for
absorption of peptides with more than three amino acids.
18. Prodrug approach:
Proteins are labile due to susceptibility of the peptide
backbone to proteolytic cleavage, as well as their
molecular size and complex secondary, tertiary and
sometimes even quaternary structures. Therefore proteins
can be modified chemically to give more stable prodrugs
with increased plasma half-lives. Some strategies for
prodrug formation include olefenic substitution, d-amino
acid substitution, dehydro amino acid substitution,
carboxyl reduction, retro inversion modification,
polyethylene glycol (PEG) attachment to amino group and
thio‐methylene modification.
19. b) Nasal route:
Pulmonary protein delivery offers both local targeting for the
treatment of respiratory diseases and increasingly appears to be a
viable option for the delivery of proteins systemically. The lung is
easy to access, has decreased proteolytic activity compared
with the gut, and allows rapid absorption and avoidance of first-
pass metabolism for systemically delivered drugs.For those being
investigated for delivery via inhalation, the ultimate site of action
may be the airway surface (e.g. DNase), the airway cells (e.g.
cyclosporin), or the systemic circulation (e.g. insulin). Careful choice
of carrier and device can facilitate delivery to a specific area of the
lungs. Once delivered, a carrier can further influence the distribution
and rate of clearance from the site of action. Eg, Nonapeptides
Vasopressin, Oxytocin.
20. Advantages of nasal route:
• Convenient, simple, practical way of drug administration
• The high vascularization permits better absorption.
• First pass metabolism can be avoided.
• Rapid onset of action.
Disadvantages of nasal route:
• Long term use may lead to toxicity to mucosa.
• During disease states (e.g. common cold) some
alteration in the nasal environment may occur.
21. c) Buccal route:
This route offers excellent accessibility and avoids
degradation of proteins and peptides that occurs as a
result of oral administration, gastrointestinal absorption and
first-pass hepatic metabolism. Peptide absorption occurs
across oral mucosa by passive diffusion and it is unlikely
that there is a carrier-mediated transport mechanism.
22. Various strategies employed for buccal delivery:
• Adhesive tablets, polymer used can be
hydroxypropylcellulose.
• Adhesive gels, using polyacrylic acid and
polymethacrylate as gel forming polymers.
• Adhesive patches.
• Addition of penetration enhancers such as fatty acids,
cyclodextrins,surfactants etc.
Thyrotropin-releasing hormone, tripeptide, oxytocin,
vasopressin ,calcitonin, insulin have been applied to this
route.
23. Advantages of buccal route:
• It is robust, much less sensitive to irreversible
irritation even on long term treatment.Prevention from
enzymatic attack. Well acceptable by patients.
• Easy to administer, and it is painless.
Disadvantages of buccal route:
• Surface area is less.
• Difficult to handle in case of having food and drinks.
24. d) Ocular route :
The ocular Route is the site of choice for the localized delivery
of opthalmologically active peptides and proteins for the
treatment of ocular disease that affect the anterior segment
tissues of eye. The use of nanoparticles, liposomes,
gels,ocular inserts, bioadhesives or surfactants are
necessary to enhance Ocular absorption of proteins or
peptides. The polypeptide antibiotics like tyrothricin,
gramicidin, tyrocidine, bacitracin and polymyxins have often
been considered potential candidates for achieving local
pharmacological actions in the eyes.
25. Proteins or peptides with opthalmological
activities:
• Affect aqueous humor dynamics: Calcitonin gene
related factors.
• Immunomodulating activities: Cyclosporine, interferons.
• Act on inflammation : Substance P, enkephalins.
• Affect wound healing: Epidermal growth factor,
fibronectin.
26. Advantages of ocular route:
• Localised action can be obtained.
• Painless approaches can be formulated.
Disavantages of ocular route:
• The systemic bioavailability achieved by this route is
very low.
• Ocular tissues are sensitive to the presence of foreign
substances and patient acceptance could be rather
low.
27. e) Rectal route:
The coadministration of an absorption promoting
adjuvants such as sodium glycocholate, has been
reported to enhance the rectal absorption of insulin. Bile
salts, such as sodium salts of cholic, deoxycholic and
glycocholic acids, have also been shown to enhance the
rectal absorption of insulin in rats and human volunteers.
Vasopressin and its analogs, pentagastrin and gastrin,
calcitonin analogs,and human albumin have been
investigated for rectal delivery of protein or peptide
based pharmaceuticals.
28. Advantages of rectal delivery:
• It is highly vascularized.
• It avoids first pass or presystemic metabolism.
• It is suitable for drugs that cause nausea/vomiting and
irritate GI mucosa on oral administration.
• A large dose of drugs can be administered.
29. f) Transdermal route:
Transdermal delivery of peptides and proteins avoids the
disadvantages associated with the invasive parenteral
route of administration and other alternative routes such
as the pulmonary and nasal routes. Since proteins have a
large size and are hydrophilic in nature, they cannot
permeate passively across the skin due to the stratum
corneum which allows the transport of only small
lipophilic drug molecules. Enhancement techniques such
as chemical enhancers, iontophoresis, microneedles,
sonophoresis aid in the delivery of proteins by overcoming
the skin barrier in different ways.
30. Approaches for transdermal delivery:
• Iontophoresis : It is use of electric current to drive
charged drug molecules into skin by placing them under
an electrode of like charged. For eg, DC Iontophoresis,
Pulse DC iontophoresis.
• Phonophoresis: In this method ultrasound is applied via
a coupling contact agent to the skin. Insulin, IFN γ,
erythropoietin can be delivered by this method.
• Penetration enhancers: Penetration enhancers like
oleic acid, dimethylsulphoxide. Surfactants have been
used for topical delivery of peptide or proteins.
31. • Prodrugs: Prodrug with modified physicochemical
characteristic permeated well across the skin. LHRH, TRH,
neurotensin can be delivered by this method.
Advantages of transdermal route:
• Avoids the hepatic first‐pass effect and gastrointestinal
breakdown.
• Provides controlled and sustained administration, particularly
suitable for the treatment of chronic disease.
• Enables self-administration and improves patient compliance,
due to its convenience and ease of use.
32. Disadvantages of transdermal route:
• A low rate of permeation for most of protein drugs due
to their large molecular weight.
• Because the skin has a relatively low proteolytic
activity, the peptide drugs have poor skin permeability.
33. Paracellular delivery of peptides—a rational approach:
Currently, a new route-the paracellular pathway,is being
explored for delivery of peptides. As opposed to the
transcellular pathway, the paracellular pathway is a water-
filled pathway, which is amicable to the delivery of polar
molecules like peptides and proteins. Another advantage is
that by traversing through the area between the two cells
the peptide also circumvents the intracellular lysosomal
enzymes. Eg,Polysaccharide hydrogels useful in the
development of controlled release formulations for protein
drugs. Polysaccharide microspheres, Microencapsulation
of protein drugs etc.
35. Development of delivery system for peptide
based pharmaceuticals
1. FORMULATION CONSIDERATIONS-
• Preformulation studies.
• Surface adsoption behaviour.
• Aggregation behaviour of protiens and peptide molecules.
2. PHARMACOKINETIC CONSIDERATIONS-
• Metabolic degradation of proteins and poeptides in liver,
kidney, non-targeted tissues and even at the site of
administration by peptidases and proteinases.
36. 3. ANALYTICAL CONSIDERATIONS-
• Bioassays
• Chromatography - HPLC
• Electrophoretic methods
• Fast atom bombardment mass spectroscopy
• Immunoassays
4. REGULATORY CONSIDERATIONS-
• FDA,EPA(environmental protection
agency),OSHA(occupational safety and health
administration, and U.S.Department of agriculture.
37. Barriers to protein drug delivery.
• Enzymatic barriers
• Intestinal epithelial barrier.
• Cappilary endothelial barrier.
• Blood brain barrier.
38. REFERENCE
• A.Semalty, Mona Semalty, R. Singh, S. K. Saraf 1 & Shubhini Saraf 2
“Properties and Formulation of Oral Drug Delivery Systems of Protein and
Peptides”,Indian Journal of Pharmaceutical Sciences,Department of
Pharmaceutical Sciences, H.N.B. Garhwal University, Srinagar,India,November -
December 2007.
• Abdul Muheem a, Faiyaz Shakeel b, Mohammad Asadullah Jahangir c,
Mohammed Anwar a, Neha Mallick a, Gaurav Kumar Jain a, Musarrat Husain
Warsi a, Farhan Jalees Ahmad a, “ A review on the strategies for oral
delivery of proteins and peptides and their clinical perspectives”,Saudi
Pharmaceutical Journal,Received 20 March 2014; accepted 6 June
2014,Available online 16 June 2014.
• Ratnaparkhi M.P.,* Chaudhari S.P., Pandya V.A.,Department of Pharmaceutics,
“Peptides And Proteins In Pharmaceuticals” ,International Journal of Current
Pharmaceutical Research,ISSN- 0975-7066,Vol 3, Issue 2, 2011,Marathwada
Mitra Mandal’s College of Pharmacy, Thergaon, Pune.