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: 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.
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: 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.
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 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
Colon-specific drug delivery systems (CDDS) are desirable for the treatment of a range of local diseases such as ulcerative colitis, amebiasis ,irritable bowel syndrome, Crohn’s disease, chronic pancreatitis and colon cancer.
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)
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 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
Colon-specific drug delivery systems (CDDS) are desirable for the treatment of a range of local diseases such as ulcerative colitis, amebiasis ,irritable bowel syndrome, Crohn’s disease, chronic pancreatitis and colon cancer.
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)
SMEDDS consists of a mixture of drugs, oils, surfactants and co- surfactants. Gentle mixing of these ingredients in aqueous media generates micro emulsions with a droplet size in a range of 10-100 nm.
Aerosol or Pressurized package is defined as ―A system that depends on the power of a compressed gas or liquefied gas to expel the contents from the container.
Pharmacopoeia is the official book of standards for drugs prepared by any country or regulatory body to specify the standards of identity, purity and strength for the drugs imported, manufactured or distributed throughout the country or a specific region.
QA Paediatric dentistry department, Hospital Melaka 2020Azreen Aj
QA study - To improve the 6th monthly recall rate post-comprehensive dental treatment under general anaesthesia in paediatric dentistry department, Hospital Melaka
We understand the unique challenges pickleball players face and are committed to helping you stay healthy and active. In this presentation, we’ll explore the three most common pickleball injuries and provide strategies for prevention and treatment.
The dimensions of healthcare quality refer to various attributes or aspects that define the standard of healthcare services. These dimensions are used to evaluate, measure, and improve the quality of care provided to patients. A comprehensive understanding of these dimensions ensures that healthcare systems can address various aspects of patient care effectively and holistically. Dimensions of Healthcare Quality and Performance of care include the following; Appropriateness, Availability, Competence, Continuity, Effectiveness, Efficiency, Efficacy, Prevention, Respect and Care, Safety as well as Timeliness.
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Medical Technology Tackles New Health Care Demand - Research Report - March 2...pchutichetpong
M Capital Group (“MCG”) predicts that with, against, despite, and even without the global pandemic, the medical technology (MedTech) industry shows signs of continuous healthy growth, driven by smaller, faster, and cheaper devices, growing demand for home-based applications, technological innovation, strategic acquisitions, investments, and SPAC listings. MCG predicts that this should reflects itself in annual growth of over 6%, well beyond 2028.
According to Chris Mouchabhani, Managing Partner at M Capital Group, “Despite all economic scenarios that one may consider, beyond overall economic shocks, medical technology should remain one of the most promising and robust sectors over the short to medium term and well beyond 2028.”
There is a movement towards home-based care for the elderly, next generation scanning and MRI devices, wearable technology, artificial intelligence incorporation, and online connectivity. Experts also see a focus on predictive, preventive, personalized, participatory, and precision medicine, with rising levels of integration of home care and technological innovation.
The average cost of treatment has been rising across the board, creating additional financial burdens to governments, healthcare providers and insurance companies. According to MCG, cost-per-inpatient-stay in the United States alone rose on average annually by over 13% between 2014 to 2021, leading MedTech to focus research efforts on optimized medical equipment at lower price points, whilst emphasizing portability and ease of use. Namely, 46% of the 1,008 medical technology companies in the 2021 MedTech Innovator (“MTI”) database are focusing on prevention, wellness, detection, or diagnosis, signaling a clear push for preventive care to also tackle costs.
In addition, there has also been a lasting impact on consumer and medical demand for home care, supported by the pandemic. Lockdowns, closure of care facilities, and healthcare systems subjected to capacity pressure, accelerated demand away from traditional inpatient care. Now, outpatient care solutions are driving industry production, with nearly 70% of recent diagnostics start-up companies producing products in areas such as ambulatory clinics, at-home care, and self-administered diagnostics.
CRISPR-Cas9, a revolutionary gene-editing tool, holds immense potential to reshape medicine, agriculture, and our understanding of life. But like any powerful tool, it comes with ethical considerations.
Unveiling CRISPR: This naturally occurring bacterial defense system (crRNA & Cas9 protein) fights viruses. Scientists repurposed it for precise gene editing (correction, deletion, insertion) by targeting specific DNA sequences.
The Promise: CRISPR offers exciting possibilities:
Gene Therapy: Correcting genetic diseases like cystic fibrosis.
Agriculture: Engineering crops resistant to pests and harsh environments.
Research: Studying gene function to unlock new knowledge.
The Peril: Ethical concerns demand attention:
Off-target Effects: Unintended DNA edits can have unforeseen consequences.
Eugenics: Misusing CRISPR for designer babies raises social and ethical questions.
Equity: High costs could limit access to this potentially life-saving technology.
The Path Forward: Responsible development is crucial:
International Collaboration: Clear guidelines are needed for research and human trials.
Public Education: Open discussions ensure informed decisions about CRISPR.
Prioritize Safety and Ethics: Safety and ethical principles must be paramount.
CRISPR offers a powerful tool for a better future, but responsible development and addressing ethical concerns are essential. By prioritizing safety, fostering open dialogue, and ensuring equitable access, we can harness CRISPR's power for the benefit of all. (2998 characters)
One of the most developed cities of India, the city of Chennai is the capital of Tamilnadu and many people from different parts of India come here to earn their bread and butter. Being a metropolitan, the city is filled with towering building and beaches but the sad part as with almost every Indian city
India Clinical Trials Market: Industry Size and Growth Trends [2030] Analyzed...Kumar Satyam
According to TechSci Research report, "India Clinical Trials Market- By Region, Competition, Forecast & Opportunities, 2030F," the India Clinical Trials Market was valued at USD 2.05 billion in 2024 and is projected to grow at a compound annual growth rate (CAGR) of 8.64% through 2030. The market is driven by a variety of factors, making India an attractive destination for pharmaceutical companies and researchers. India's vast and diverse patient population, cost-effective operational environment, and a large pool of skilled medical professionals contribute significantly to the market's growth. Additionally, increasing government support in streamlining regulations and the growing prevalence of lifestyle diseases further propel the clinical trials market.
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CHAPTER 1 SEMESTER V PREVENTIVE-PEDIATRICS.pdfSachin Sharma
This content provides an overview of preventive pediatrics. It defines preventive pediatrics as preventing disease and promoting children's physical, mental, and social well-being to achieve positive health. It discusses antenatal, postnatal, and social preventive pediatrics. It also covers various child health programs like immunization, breastfeeding, ICDS, and the roles of organizations like WHO, UNICEF, and nurses in preventive pediatrics.
5. 1) ORAL ROUTE :-
Oral route is the most popular route of delivery from the patient’s point of
view. Main advantages of this route are convenience, acceptability and high
patient compliance.
The main barriers to successful oral delivery of protein and peptides are
similar to that of traditional drug candidates, but these are more pronounced
in the case o fpeptide/protein moieties.
The main barriers to effective oral delivery are :-
Poor intrinsic permeability of peptides/proteins across biological membranes.
Susceptibility to enzymatic attack by intestinal proteases and peptidases.
Rapid post-absorptive clearance.
Physical instability like aggregation and adsorption.
7. a). CHEMICAL MODIFICATION :-
The Chemical Modification of Protein and Peptide Drug is Important to
Improve the Enzymatic Stability as well as Membrane Permeations.
a.1) Amino acid modification:-
Post-translational modifications can occur on the amino acid side chains or
at the protein's C-or N- termini .They can extend the chemical repertoire of
the 20 standard amino acids by modifying an existing functional group or
introducing a new one such as phosphate.
Phosphorylation is a very common mechanism for regulating the activity of
enzymes and is the most common post-translational modification.
Amino acid
(polar)
Phosphorylation Amino acid
( non-polar)
8. a.2) Lipidation:-
Attachment of lipid molecules to the protein structure.
Hydrophobic groups for membrane localization:-
Myristoylation , attachment of myristate.
Palmitoylation , attachment of palmitate.
Isoprenylation or prenylation, the addition of an isoprenoid group.
Cofactors for enhanced enzymatic activity:-
Lipoylation, attachment of a lipoate functional group.
Flavin moiety may be covalently attached.
9. b) Penetration Enhancer:-
Peptide/protein drug moieties, due to their molecular size, often
require penetration enhancers to achieve therapeutically significant
levels of luminal absorption.
Penetration enhancers is responsible for the Disruption of the
Mucosal Barriers.
Surfactant Polysorbate , SLS, Pluronic F-68
Chelating agent EDTA
Bile salt sodium cholate and deoxycholate
Mucoadhesive
polymeric system
Thiomers , Cellulose derivatives
Other example Fatty acids, Phospholilpid
10. C) Carrier System:-
This strategy is particularly applicable in the case of poorly absorbed
peptides/proteins, which are unstable in the Gastro intestinal (GI) lumen
and their targeting to a specific tissue or organ is to be affected.
The proper designing of the delivery system not only protects the drug from
gastrointestinal degrading components in the physical environment of the
formulation prior to absorption, but also localized the drug at or near the
cellular membrane to maximize the driving force for passive permeation.
C.1) lipid based carrier system:-
C.1.1) Liposomes :-
Liposomes are spherical, self-closed structure formed by one or several
lipid bilayer with an aqueous phase inside.
11. Liposomes are biocompatible and can both entrap and protect the protein and
peptide in their internal core.
To deliver liposomes to the brain, they can be firstly modified into long
circulation vesicles by decreasing particle size (< 100 nm) or by linking
polyethylene glycol (PEG) chains to their surface.
Method of Preparation
Liposome
12. C1.2) Emulsion:-
An emulsion is a well-blended mixture of two immiscible liquids such as oil
and water in the presence of emulsifying or surface-active agents .
Multiple emulsions such as oil in-water-in-oil (O/W/O) and water-in-oil-in-water
(W/O/W) emulsions are often used for delayed or controlled drug release.
Self-nanoemulsifying drug delivery systems (SNEDDS) have received
considerable attention as a promising alternative to orally administered
emulsions due to their high physical stability and ease of manufacture.
SNEDDS consist of oils, surfactants, co-solvents/co-surfactants, and drugs.
Compared to conventional W/O/W emulsions, SNEDDS have some
advantages as an oral delivery system for protein drugs in terms of better
stability, better oral bioavailability, and easier particle size control.
14. C.2) Polymer Based Carrier System:-
C.2.1) Hydrogels :-
Hydrogels are three-dimensional polymeric networks composed of cross-
linked hydrophilic and biocompatible polymers, which also exhibit a
thermodynamic compatibility with water allowing them to swell in aqueous
media.
Among various polymers, 2-hydroxyethyl methacrylate, ethylene glycol
dimethylacrylate, N-isopropyl acrylamide, acrylic acid, methacrylic acid (MAA),
polyethylene glycol (PEG) and polyvinyl alcohol (PVA) are commonly used in
hydrogels for protein delivery.
Alginate and xanthan gum-based hydrogel systems seem to be suitable for
protein delivery via the oral route of administration.
15. C.2.2) Nanoparticles:-
Nanoparticles are solid, colloidal particles consisting of macromolecular
substances that vary in size from 10 nm to 1000 nm.
Typically, the drug of interest is dissolved, entrapped, adsorbed, attached
and/or encapsulated into or onto a nano matrix.
Polymers are used in the preparation of nanoparticles:-
Polylactic acid (PLA),
Polylactic-co-glycolic acid(PLGA)
Chitosan
Gelatin,
Polymethylmethacrylates
Poly-alkyl-cyanoacrylate.
16.
17. D) Enzyme Inhibitor:-
In addition to direct modifications, another method to increase oral peptide
bioavailability is to coadminister with enzyme inhibitors.
These enzyme inhibitors are usually more effective in the large intestine
than the small intestine due to the large quantity and variety of proteases in
the small intestine.
Insulin with enzyme inhibitor (Aprotinin, bacitracin, betatin) which result in
significance reduction in insulin digestion and improve in its intestinal
absorption profile
Enzyme inhibition compound
Metalloprotease EDTA
Aminopeptidases Bestain & Bacitracin
Metalloendoprotease Phosphoramidon
Cystinyl Proteases Papain, Endopeptidase
18.
19. Buccal membrane has numerous elastic fibers in the dermis, which is
another barrier for diffusion of drug across the buccal membrane.
The barriers for efficient drug absorption are:
Mucus layer covering the oral epithelium.
Epithelial barriers.
Peptidases in the saliva and the mucus layer and microbial flora.
The buccal peptide absorption is assumed to be via passive absorption
mechanism.
Various parameter that influence the extent of buccal peptide absorption are
molecular weight, polarity, conformation, dissociation and enzymatic and
chemical stability.
2.) Buccal Route :-
20. various strategies employed for Buccal Delivery
Adhesive
tablets
Adhesive
patches
Adhesive gels
a.) Adhesive Tablets:-
Buccal tablets are small, flat and oval, with a
diameter approximately 5-8 mm. They soften,
attach to the mucosa, and are retained in
position until dissolution and release is
complete.
These tablets can be applied to different
sites in the oral cavity, including the
palate,the mucosa lining the check, as well
as between the lip and the gum.
21. b). Adhesive Gels :-
Viscous adhesive gels have been designed for local therapy using polyacrylic
acid and polymethacrylate as gel forming polymers.
Gels are reported to prolong residence time on the oral mucosa to a
significant level. This not only improves absorption but also allows for
sustained release of the active principle.
C). Adhesive Patches :-
Patches are laminates consisting of an impermeable backing layer, a drug-
containing reservoir layer from which the drug is released in a controlled
manner, and a bioadhesive surface for mucosal attachment.
22. Formulation of Mucoadhesive buccal Film
Formulation of Mucoadhesive buccal Film
API
Bioadhesive
polymer
Plasticizer
Penetration
Enhancer
Backing
membrane
Agarose
chitosan
gelatin
hyaluronic acid
Polyacrylates
polyoxyethylene
glycerol,
propylene
glycol,
PEG 400,
castor oil
Polysorbate
EDTA
sodium cholate
and deoxycholate
Thiomers
Cellulose
derivatives
carbopol
magnesium
stearate
HPMC
HPC
CMC
23.
24. 3.) Nasal Route:-
Generally, the intranasal route is suited for the intermittent delivery of highly
potent peptide/protein drugs having low molecular weight.
Peptidal drug moieties like calcitonin, ACTH, and interferon are reported to
have appreciable absorption through nasal mucosa.
Nasal route is chiefly use to delivery of protein drug.
Barriers to systemic absorption through nasal route :-
Extent of absorption varies with the mucus secretion and mucus turnover.
Peptidases and proteases present in the mucus or associated with nasal
membrane serve as enzymatic barrier in protein/peptide absorption.
Types of
Dosage Form
Nasal Spray Aerosol Nasal Drops
25. Various approaches for Nasal Delivery of peptide/protein
drugs
Increase
nasal blood
flow
Permeation
enhancer
and enzyme
inhibitor
Dissociation
of
Aggregation
pH
Modification
Viscosity
modification
a.) Viscosity modification :-
The clearance time from the nasal cavity can be delayed by using solutions
with higher viscosity.
For example the half time of clearance could be increased significantly with
0.6 % of hydroxypropyl methylcellulose.
26. b). pH Modification:-
Peptides and proteins usually exhibit the lowest solubility at their isoelectric
point. Thus, by adjusting the pH further away from the isoelectric point of a
particular peptide, its solubility can be increased.
For example nasal absorption of insulin was observed with sodium
deoxycholate, that insulin is capable of crossing the nasal membrane in an
acidic medium.
Examples of buffer used in nasal spray sodium phosphate, Sodium citrate,
citric acid.
c). Dissociation of Aggregation:-
Proteins are likely to form higher-order aggregates in solution.
For instance at pH 7.0, protein exists in solution chiefly as hexameric
aggregates
27. Protein fails to cross the nasal membrane.
Sodium deoxycholate disrupts the formation of protein hexamer or
dissociation of protein hexamer to dimer or monomer.
d). Permeation enhancer and enzyme inhibitor :-
They increase the fluidity of the lipid bilayer membrane and open up
aqueous pores as a result of calcium ion chelation.
Peptidase inhibitors enhance the absorption by suppressing peptidase
activity in both the mucus and mucosal cells.
Enzyme inhibitor Permeation enhancer
EDTA
Bile Salts
Polysorbate
EDTA
sodium cholate and
deoxycholate
Thiomers
Cellulose derivatives
28. e). Increase Nasal flow:-
With an increase in local nasal blood flow an enhancement in nasal peptide
absorption has been reported. This occurs due to concentration gradient of
peptide passive diffusion.
Vasoactive agents, which are known to enhance nasal blood flow, include
histamine, prostaglandin E1 and beta-adrenergic agonist.
Different nasal delivery systems like drops, sprays and inhalers have variable
results in terms of intensity, duration of effect. Nasal drops produce far greater
pathologic changes and faster clearance than the nasal sprays and inhalers.
Metered dose aerosol and metered dose pump can achieve accurate dose
dispensation and good distribution in the nasal cavity.
Delivery system :-
29.
30. 4.) Transdermal Route:-
Transdermal is a route of administration wherein active ingredients are
delivered across the skin for systemic distribution.
Advantages of Transdermal Route for peptide/protein Delivery are:
Better and improved patient compliance.
Elimination of hepatic first pass phenomenon.
Controlled administration is possible and thereby avoidance of toxic effects.
Also drugs with shorter half-life can be administered.
Limitations of Transdermal Route for peptide/protein Delivery are:
A low rate of permeation for most protein drugs due to their large molecular
weight and hydrophilicity and lipophilic nature of the stratum corneum .
High intra and inter patient variability.
31. Various approaches for Transdermal delivery Route of
peptidal drugs
Iontophoresis Sonophoresis Electroporation
Microneedle
technology
a).Iontophoresis:-
Iontophoresis is a method that induces migration of ions or charged
molecules when an electric current is allowed to flow through an electrolyte
medium.
32. To undergo Iontophoresis protein/and peptide
molecules must carry charge. To achieve this
pH and ionic strength of solution are controlled.
Protein/and peptide are repelled by the same
charge on electrode and penetrate through the
skin under the influence of electric current.
The two electrodes are placed on the stratum
corneum, one of the electrode drug is loaded
(reservoir electrode) and current is applied
which increased the permeability of skin and
drug molecule flow through epidermis →→→
dermis→ papillary layer →→ subdermal
tissue→→blood circulation
Iontophoresis
33. b) Electroporation :-
Electroporation utilizes very short pulses of high voltages (between 10 and
100 V) to perforate the skin.
Similar to iontophoresis , application of electroporation breaches only the
stratum corneum, characterizing it as another non-invasive method for drug
introduction.
Application of an electric current disrupts the structure of these lipids, allowing
molecules to penetrate the skin. In addition, delivery of drug can be increased
using this method by increasing the voltage, number of pulses and duration of
pulses to levels still viewed as safe for the patient.
34. c). Sonophoresis :-
Sonophoresis, also referred to as cavitational ultrasound, relies on the
application of sound waves to the skin to increase its permeability.
Sonophoresis achieves this task by targeting the lipid bilayers embedded in
the stratum corneum.
Sound waves, generally between 20–100 kHz, are believed to cause an
increase in pore sizes on the skin (increased fluidity in these lipid bilayers),
thus allowing drug penetration transcellularly through the stratum corneum
35. d). Microneedle technology:-
Microneedle technology involves the use of small needles that create small
pores in the skin, allowing drug passage across the outermost physical barrier.
These microneedles are designed to breach only the stratum corneum.
Methods :-
One such method involves a two step approach, where the needles are used
to puncture the skin to create pores, followed by topical administration of the
drug.
Another method includes coating the microneedles themselves with drugs,
allowing the drug to then enter the body after the skin is treated with the
needle.
A third method includes encapsulating the drug in biodegradable
microneedles, slowly releasing the drug as the needles degrade.
38. 5.)Parenteral Route :-
Parenteral mode of drug delivery has been the major route of choice for
protein/peptide, owing to their poor absorption and metabolic instability when
given by other alternative routes.
The parenteral drug delivery system includes Intravenous, intramuscular,
subcutaneous, intraperitoneal, intrathecal use.
Carriers System
Liposome
Nano particles
Microsphere Emulsion
40. a). On Demand System :-
Externally augmented demand delivery systems are particularly beneficial in
the delivery of polypeptides like insulin.
The device consists of an ethylene-vinyl acetate matrix with magnetic beads
or cylinders.
The magnetic beads alternately compress and expand the matrix in the
presence of magnetic field.
On exposure to external oscillating magnetic field the drug release was
increased up to 30 times. On removal of the magnetic field, the drug release
rates returned to normal.
41. b.)Pumps:-
Pumps differ from other diffusion based system in that primary driving force
for delivery is the pressure difference and not the concentration difference of
the drug between the formulation and the surroundings. Pressurizing the drug
reservoir, by osmotic action or by direct mechanical actuation, can generate
this pressure difference to affect drug release. The pump can either be
implantable or externally portable.
b.1) Mechanical pumps:-
Mechanical pumps are technically simple,
rugged and can be easily manipulated to
deliver Peptidal drugs in several different
wave form. But the prime concerns are in
terms of its susceptibility to mechanical
failure, high power requirement and
relatively large size.
42. b.2) Osmotic pumps:-
Osmotic Pump have been used extensively for delivery of a large number
of peptide/proteins drugs in animals. These pumps can be implanted
subcutaneously. Some of the representative examples of drugs that have
been delivered in osmotic pumps include insulin, ACTH, calcitonin, LHRH,
growth hormone, neurotensin and vasopressin
43. C) Self regulated system:-
Glucose sensor sense
the Glucose level
Transmit Signal to the
insulin Pump
Then sensor transmit
signal to stop the insulin
pump
Insulin Pump deliver
Insulin to infusion set