SlideShare a Scribd company logo
1 of 7
Download to read offline
Huateng Pharma https://us.huatengsci.com
Overview of Oral Delivery Strategies for
Peptides
Peptides are short chains of amino acids linked by peptide bonds. Compared
with traditional small molecule drugs, peptide drugs are featured with strong
drugability, high activity, high specificity, low toxicity, and no drug-drug
interactions; compared with protein drugs, peptide drugs have the advantages
of lower production cost, simpler R&D, and no immunogenicity. Therefore,
since the discovery of insulin in 1920, peptide drugs have received increasing
attention. Currently, more than 100 peptide drugs have been approved for
marketing, with clinical applications covering metabolic diseases, cancer,
neurological diseases, immune diseases, etc.
Although peptide drugs have a promising therapeutic future, they also have
certain drawbacks. The presence of peptidases results in peptide drugs
usually having a short half-life, and this instability affects drug development
and efficacy. Problems such as low oral efficiency and poor cellular uptake can
also affect late-stage drug formation.
Oral administration is gradually becoming a research focus as a safe and
compliant route of drug delivery. In recent years, research on enhancing the
oral absorption of peptides has made great progress in both preclinical and
clinical trials. In 2019, the approval of oral semaglutide, developed by Novo
Nordisk and Emisphere Technologies, became a major milestone in the field of
oral peptides.
Strategies for oral delivery of proteins peptides
Since the discovery of insulin in 1920, oral peptide research has never stopped,
and more than 20 strategies for delivering peptides orally have been reported.
As shown in Figure 1, they include enteric coating, pH modulators, enzyme
inhibitors; PEGylation, cyclization, prodrugs; mucosal adsorption,
microneedling; absorption enhancers, nanotechnology and so on. Among
them, the main delivery strategies to get industrial translation are chemical
modifications, pH modulators/enzyme inhibitors, permeation enhancers, and
SNEDDS.
Huateng Pharma https://us.huatengsci.com
Figure 1. Strategic approaches for oral delivery of peptides
source: reference [1]
Chemical Modifications
Chemical modifications, which are mainly aimed at improving the half-life of
peptides, include PEGylation (polyethylene glycol), glycosylation, lipidation,
and using adjuvant molecules to enhance delivery. Among these,
the combination of PEG with peptides improves thermal stability, resists
protease degradation, reduces antigenicity, and prolongs half-life in vivo. In
addition to PEG, lipidation and glycosylation of peptide drugs can also improve
the enzyme stability of peptides and so on. For example, by fatty acid acylation
of the lysine in position 26, semaglutide improves efficacy, enhances
resistance to enzymatic degradation, improves plasma stability, and
significantly prolongs half-life.
Note: Huateng Pharma provides high quality PEG derivatives for your
PEGylation of peptide.
Huateng Pharma https://us.huatengsci.com
Figure 2. semaglutide structure
In addition, cyclic peptides are also one of the key areas of oral peptide
research. Peptide cyclization is used to make peptides insensitive to
hydrolases by removing the exposed C- and N-terminals from the peptide
molecule. In addition, cyclization reduces the exposure of polar atoms to the
surrounding environment by folding the peptide into a biologically active
conformation, thereby improving the stability and bioavailability of the peptide
for oral administration.
Although chemical modification of peptides has been extensively studied, it
remains a challenge in terms of its industrial feasibility and high cost.
pH modulation/Enteric Coating
The pH environment of the GI tract leads to the hydrolysis and conformational
changes of peptides, as well as their enzymatic degradation at that pH. It has
been shown that peptides are relatively stable only in a narrow pH range
similar to their isoelectric point.
The activity of GI enzymes is closely related to their pH environment. For
example, pepsin can only degrade peptides in an acidic environment, ,
however, pepsin starts to lose their effect when the pH is over 3.
In the development strategy for oral semaglutide (Rybelsus®), one of the roles
of the excipient SNAC is to raise the local intragastric pH to protect
semaglutide from degradation by pepsin. For octreotide (Mycapssa®), enteric
coating was used directly to avoid octreotide release in the stomach. In
addition, Tarsa Therapeutics (Philadelphia, USA) has successfully completed
a phase III trial for oral delivery of sCT (ORACAL) which comprises of an
enteric coated capsule to bypass the stomach and citric acid to modulate the
pH microenvironment in intestine.
Huateng Pharma https://us.huatengsci.com
Figure 3. SNAC Technology, source: Novo Nordisk official website
Absorption enhancers
The addition of absorption enhancers to drug prescriptions is one of the
commonly used means of oral formulation. Since a study in 1961 found that
EDTA improved the oral absorption of heparin in dogs, absorption enhancers
have received a lot of attention in pharmaceutical and biomaterials science.
With the rapid development of these disciplines, excipients with better safety
and better absorption-promoting effects are emerging. Absorption enhancers
can be categorized according to their role as paracellular enhancers,
transcellular enhancers, and both paracellular and transcellular enhancers.
There are tight junctions, adhesion junctions and desmosome junctions
between cells, and these complexes maintain the morphology and integrity of
the intestinal wall structure, preventing the passage of bacteria, and
undigested proteins through the cellular interstitial space. Chelating agents
can reduce Ca2+ concentration by chelating with extracellular Ca2+, which in
turn leads to an increase in cellular paracellular permeability through a series
of signaling pathways; the effect is reversible, and cellular permeability
recovers after an increase in Ca2+ concentration. Commonly used chelating
agents include EDTA, citric acid, etc. Oramed Pharma uses EDTA as
absorption enhancers, and clinical studies have shown that the oral relative
bioavailability of insulin in the group employing EDTA was 20% higher when
compared to chitosan nanoparticles of insulin.
Most surfactants, including sodium caprylate and their derivatives, and bile
salts, are commonly used transcellular absorption enhancers, which make
drugs more accessible to cells by increasing the permeability of cell
membranes or increasing the lipophilicity of the drug. For example, one of the
reasons why SNAC, an excipient in oral semaglutide prescription, enhances
Huateng Pharma https://us.huatengsci.com
absorption is that it promotes the monomerization of semaglutide and its
interaction with the plasma membrane, thus increasing its permeability. Oral
bioavailability has also been enhanced by the use of 5-CNAC in a
clinical-stage sCT (SMC021), which is in phase III clinical trials.
In addition, such as sodium decanoate, sodium octanoate also has the effect
of enhancing both paracellular and transcellular absorption. Sodium
decanoate can increase intracellular Ca2+ concentration, phosphorylate
myosin light chain after signaling to open cellular paracellular pathway, and
also has the effect of disturbing the plasma membrane to enhance intestinal
permeability.
SNEDDS
Self-nanoemulsifying drug delivery systems (SNEDDS) were regarded as an
important strategy for improving oral absorption of drug molecules.
Among the marketed products, cyclosporin A (Neoral® and Sandimmune®),
as well as Voclosporin (wupkynis®) employ SNEDDS technology. SNEDDS is
a lipid-based drug delivery system in which the formulation consists mainly of
an oil phase, a surfactant and a co-surfactant. After oral administration, the
self-microemulsions spontaneously and rapidly form O/W type drug-carrying
microemulsions in the gastrointestinal fluid under gastrointestinal peristalsis,
with droplet sizes <100 nm. The droplets formed in the gastrointestinal tract
are small in size and widely distributed, which improves the concentration of
difficult-to-solve drugs in the gastrointestinal tract and promotes osmotic
transmembrane absorption. During the process of emulsion breaking and
digestion, the fatty acids digested from the core oil, the bile acid salts secreted
in the body and the phospholipids in the food can form mixed micelles, which
wraps the raw materials into the micelles, thus promoting the absorption of the
raw materials by the osmotic, transporter, cytosolic and lymphatic pathways.
Some lipid excipients such as C8 octanoic acid oil, C10 decanoic acid
derivatives also have a certain degree of pro-absorption effect.
However, it should be noted that Voclosporin is essentially a structural analog
of cyclosporin A, and both are water-insoluble and lipophilic drugs. SNEDDS is
not suitable for drugs with strong water solubility, and at the same time, for
drugs with poor hydrophilic and lipophilic properties, there is a possibility that
the drug may be heavily enriched in the interfacial layer after the formation of
the microemulsion, leading to precipitation or degradation.
Overview of The Current Clinical Studies
Cyclosporin A (Sandimmune®), a cyclic peptide with a molecular weight of
1202, was the first FDA-approved oral peptide. 5 years later, Novartis
developed and approved Neoral®, a modified version of cyclosporin A. In 2019,
Huateng Pharma https://us.huatengsci.com
an oral formulation of semaglutide, developed by Novo Nordisk, was approved
by the FDA for the treatment of type II diabetes mellitus. Octreotide
extended-release capsules (Mycapssa®) were approved for marketing by the
FDA in 2020. These last two oral peptide products are revolutionizing the field
of oral peptides.
There are currently 17 oral peptide drugs successfully marketed worldwide, of
which 8 are absorbed into the bloodstream after oral administration.
Table. Marketed oral peptide
Conslusion
We provide an overview of the current landscape of oral peptides in marketing
and clinical studies, a review of the forms of delivery used, and a summary and
analysis of the common strategies used for oral peptides that have been
successfully translated into industry. In fact, each successfully marketed oral
peptide may include a combination of different absorption enhancing strategies,
such as octreotide (Mycapssa®), which uses both absorption enhancers and
enteric coating technology, somatostatin (Rybelsus®), which has an optimized
chemical structure, and excipient SNAC, which acts as both a pH modulator
and an absorption enhancer.
With the emergence of more oral peptides and the availability of new functional
excipients, oral peptide delivery technologies capable of overcoming human
physiological barriers will continue to emerge, facilitating the wider clinical
application of peptides.
Huateng Pharma is known worldwide for a variety of pharmaceutical
intermediates used in research and development. We can provide antidiabetic
drug intermediates such as semaglutide intermediates, liraglutide
Huateng Pharma https://us.huatengsci.com
intermediates, canagliflozin intermediates, dapagliflozin intermediates and em
pagliflozin intermediates for your research. We have our own factory and
make scale-up production with capacities varying from gram to kilograms and
multi tons.
References:
1. Zhu, Quangang & Chen, Zhongjian & Paul, Pijush & Lu, Yi & Wu, Wei & Qi,
Jianping. (2021). Oral delivery of proteins and peptides: Challenges, status
quo and future perspectives. Acta Pharmaceutica Sinica B. 11. 2417-2449.
10.1016/j.apsb.2021.04.001.
2. Su FY, Lin KJ, Sonaje K, Wey SP, Yen TC, Ho YC, et al. Protease inhibition
and absorption enhancement by functional nanoparticles for effective oral
insulin delivery. Biomaterials., 2012, 33:2801.
3. Pandya AK, Patravale VB. Computational avenues in oral protein and
peptide therapeutics. Drug Discov Today. 2021;26(6):1510-1520.
doi:10.1016/j.drudis.2021.03.003
4. Drucker DJ. Advances in oral peptide therapeutics. Nat RevDrug Discov.
2019 Dec 17. doi: 10.1038/s41573-019-0053-0.

More Related Content

Similar to Overview of Oral Delivery Strategies for Peptides.pdf

Formulation Development and Evaluation of Carbamazepine Fast Dissolving Tablets
Formulation Development and Evaluation of Carbamazepine Fast Dissolving TabletsFormulation Development and Evaluation of Carbamazepine Fast Dissolving Tablets
Formulation Development and Evaluation of Carbamazepine Fast Dissolving Tablets
Dr. Raghavendra Kumar Gunda
 
Formulation and Evaluation of Floating Tablet of Metoprolol Succinate
Formulation and Evaluation of Floating Tablet of Metoprolol SuccinateFormulation and Evaluation of Floating Tablet of Metoprolol Succinate
Formulation and Evaluation of Floating Tablet of Metoprolol Succinate
ijtsrd
 
Recent advances of starch based excipients used in extended-release
Recent advances of starch based excipients used in extended-releaseRecent advances of starch based excipients used in extended-release
Recent advances of starch based excipients used in extended-release
karthickravi29
 
Design, Development, and Evaluation of Nsaid Drug in Soft gel Dosage Form
Design, Development, and Evaluation of Nsaid Drug in Soft gel Dosage FormDesign, Development, and Evaluation of Nsaid Drug in Soft gel Dosage Form
Design, Development, and Evaluation of Nsaid Drug in Soft gel Dosage Form
BRNSSPublicationHubI
 

Similar to Overview of Oral Delivery Strategies for Peptides.pdf (20)

Formulation Development and Evaluation of Carbamazepine Fast Dissolving Tablets
Formulation Development and Evaluation of Carbamazepine Fast Dissolving TabletsFormulation Development and Evaluation of Carbamazepine Fast Dissolving Tablets
Formulation Development and Evaluation of Carbamazepine Fast Dissolving Tablets
 
Protein and peptide drug delivery system
Protein and peptide drug delivery systemProtein and peptide drug delivery system
Protein and peptide drug delivery system
 
Formulation and Evaluation of Floating Tablet of Metoprolol Succinate
Formulation and Evaluation of Floating Tablet of Metoprolol SuccinateFormulation and Evaluation of Floating Tablet of Metoprolol Succinate
Formulation and Evaluation of Floating Tablet of Metoprolol Succinate
 
Nasal drug delivery
Nasal drug deliveryNasal drug delivery
Nasal drug delivery
 
Rectal drug delivery systems
Rectal drug delivery systemsRectal drug delivery systems
Rectal drug delivery systems
 
NDDS.pptx
NDDS.pptxNDDS.pptx
NDDS.pptx
 
Oral drug delivery proteins
Oral drug delivery proteinsOral drug delivery proteins
Oral drug delivery proteins
 
M.Pham project presentation phase 2
M.Pham project presentation phase 2M.Pham project presentation phase 2
M.Pham project presentation phase 2
 
Protein and peptide drug delivery system
Protein and peptide drug delivery systemProtein and peptide drug delivery system
Protein and peptide drug delivery system
 
ROLE OF DOSAGE FORM IN GASTRO-INTESTINAL ABSORPTION
ROLE OF DOSAGE FORM IN GASTRO-INTESTINAL ABSORPTION ROLE OF DOSAGE FORM IN GASTRO-INTESTINAL ABSORPTION
ROLE OF DOSAGE FORM IN GASTRO-INTESTINAL ABSORPTION
 
Mouth dissolving films
Mouth dissolving filmsMouth dissolving films
Mouth dissolving films
 
02_IJPBA_1938_21.pdf
02_IJPBA_1938_21.pdf02_IJPBA_1938_21.pdf
02_IJPBA_1938_21.pdf
 
Novel Drug Delivery System for colon
Novel Drug Delivery System for colonNovel Drug Delivery System for colon
Novel Drug Delivery System for colon
 
Nasal and pulmonary dds
Nasal and pulmonary ddsNasal and pulmonary dds
Nasal and pulmonary dds
 
Recent advances of starch based excipients used in extended-release
Recent advances of starch based excipients used in extended-releaseRecent advances of starch based excipients used in extended-release
Recent advances of starch based excipients used in extended-release
 
An Outline on Various Methods Used in Formulation and Evaluation of Lansopraz...
An Outline on Various Methods Used in Formulation and Evaluation of Lansopraz...An Outline on Various Methods Used in Formulation and Evaluation of Lansopraz...
An Outline on Various Methods Used in Formulation and Evaluation of Lansopraz...
 
Drug-Delivery-Strategies-for-Poorly-Water-Soluble-Silymarin.pdf
Drug-Delivery-Strategies-for-Poorly-Water-Soluble-Silymarin.pdfDrug-Delivery-Strategies-for-Poorly-Water-Soluble-Silymarin.pdf
Drug-Delivery-Strategies-for-Poorly-Water-Soluble-Silymarin.pdf
 
Design, Development, and Evaluation of Nsaid Drug in Soft gel Dosage Form
Design, Development, and Evaluation of Nsaid Drug in Soft gel Dosage FormDesign, Development, and Evaluation of Nsaid Drug in Soft gel Dosage Form
Design, Development, and Evaluation of Nsaid Drug in Soft gel Dosage Form
 
02_IJPBA_1938_21.pdf
02_IJPBA_1938_21.pdf02_IJPBA_1938_21.pdf
02_IJPBA_1938_21.pdf
 
Bioavailability and bioequivalence study
Bioavailability and bioequivalence studyBioavailability and bioequivalence study
Bioavailability and bioequivalence study
 

More from DoriaFang

More from DoriaFang (20)

Cyclic Peptides Current Status & Future Prospects.pdf
Cyclic Peptides Current Status & Future Prospects.pdfCyclic Peptides Current Status & Future Prospects.pdf
Cyclic Peptides Current Status & Future Prospects.pdf
 
Antibody–Oligonucleotide Conjugates (AOCs) in Clinical Trials.pdf
Antibody–Oligonucleotide Conjugates (AOCs) in Clinical Trials.pdfAntibody–Oligonucleotide Conjugates (AOCs) in Clinical Trials.pdf
Antibody–Oligonucleotide Conjugates (AOCs) in Clinical Trials.pdf
 
Alzheimer's Disease Drug Development Aducanumab, Lecanemab & Donanemab.pdf
Alzheimer's Disease Drug Development Aducanumab, Lecanemab & Donanemab.pdfAlzheimer's Disease Drug Development Aducanumab, Lecanemab & Donanemab.pdf
Alzheimer's Disease Drug Development Aducanumab, Lecanemab & Donanemab.pdf
 
Claudin6 (CLDN6) A Emerging Target For Solid Tumor.pdf
Claudin6 (CLDN6) A Emerging Target For Solid Tumor.pdfClaudin6 (CLDN6) A Emerging Target For Solid Tumor.pdf
Claudin6 (CLDN6) A Emerging Target For Solid Tumor.pdf
 
ROR1 ADCs in Clinical Trials MK-2140, NBE-002 & CS5001.pdf
ROR1 ADCs in Clinical Trials MK-2140, NBE-002 & CS5001.pdfROR1 ADCs in Clinical Trials MK-2140, NBE-002 & CS5001.pdf
ROR1 ADCs in Clinical Trials MK-2140, NBE-002 & CS5001.pdf
 
Summary of Targeted Protein Degradation in Clinical Trials.pdf
Summary of Targeted Protein Degradation in Clinical Trials.pdfSummary of Targeted Protein Degradation in Clinical Trials.pdf
Summary of Targeted Protein Degradation in Clinical Trials.pdf
 
Overview of New Targets For Anti-tumor Drugs.pdf
Overview of New Targets For Anti-tumor Drugs.pdfOverview of New Targets For Anti-tumor Drugs.pdf
Overview of New Targets For Anti-tumor Drugs.pdf
 
Cleavable Linkers Used In ADC Development.pdf
Cleavable Linkers Used In ADC Development.pdfCleavable Linkers Used In ADC Development.pdf
Cleavable Linkers Used In ADC Development.pdf
 
The Role of Four Lipid Components Of LNPs.pdf
The Role of Four Lipid Components Of LNPs.pdfThe Role of Four Lipid Components Of LNPs.pdf
The Role of Four Lipid Components Of LNPs.pdf
 
Trophoblast Glycoprotein (TPGB5T4) A New Target For ADC Drugs.pdf
Trophoblast Glycoprotein (TPGB5T4) A New Target For ADC Drugs.pdfTrophoblast Glycoprotein (TPGB5T4) A New Target For ADC Drugs.pdf
Trophoblast Glycoprotein (TPGB5T4) A New Target For ADC Drugs.pdf
 
Advances in TROP-2 Directed ADCs.pdf
Advances in TROP-2 Directed ADCs.pdfAdvances in TROP-2 Directed ADCs.pdf
Advances in TROP-2 Directed ADCs.pdf
 
DS-8201 (Enhertu) A Potential ADC Drug Targeting HER2.pdf
DS-8201 (Enhertu) A Potential ADC Drug Targeting HER2.pdfDS-8201 (Enhertu) A Potential ADC Drug Targeting HER2.pdf
DS-8201 (Enhertu) A Potential ADC Drug Targeting HER2.pdf
 
List of New Anti-cancer Drugs Approved By FDA In The First Half of 2023.pdf
List of New Anti-cancer Drugs Approved By FDA In The First Half of 2023.pdfList of New Anti-cancer Drugs Approved By FDA In The First Half of 2023.pdf
List of New Anti-cancer Drugs Approved By FDA In The First Half of 2023.pdf
 
The Future Development of ADC For Cancer.pdf
The Future Development of ADC For Cancer.pdfThe Future Development of ADC For Cancer.pdf
The Future Development of ADC For Cancer.pdf
 
Summary of ADC Targets For Solid Tumors & Hematological Tumors.pdf
Summary of ADC Targets For Solid Tumors & Hematological Tumors.pdfSummary of ADC Targets For Solid Tumors & Hematological Tumors.pdf
Summary of ADC Targets For Solid Tumors & Hematological Tumors.pdf
 
New Oncology Trends ADCs, Bispecific Antibodies & CAR-T Cell.pdf
New Oncology Trends ADCs, Bispecific Antibodies & CAR-T Cell.pdfNew Oncology Trends ADCs, Bispecific Antibodies & CAR-T Cell.pdf
New Oncology Trends ADCs, Bispecific Antibodies & CAR-T Cell.pdf
 
Summary of Treatments for Multiple Myeloma.pdf
Summary of Treatments for Multiple Myeloma.pdfSummary of Treatments for Multiple Myeloma.pdf
Summary of Treatments for Multiple Myeloma.pdf
 
Bispecific Antibody-drug Conjugate Drugs In Clinical or Preclinical.pdf
Bispecific Antibody-drug Conjugate Drugs In Clinical or Preclinical.pdfBispecific Antibody-drug Conjugate Drugs In Clinical or Preclinical.pdf
Bispecific Antibody-drug Conjugate Drugs In Clinical or Preclinical.pdf
 
ADCs Targeting the HER Family.pdf
ADCs Targeting the HER Family.pdfADCs Targeting the HER Family.pdf
ADCs Targeting the HER Family.pdf
 
Nectin-4 New Antibody-Drug Conjugate (ADC) Target.pdf
Nectin-4 New Antibody-Drug Conjugate (ADC) Target.pdfNectin-4 New Antibody-Drug Conjugate (ADC) Target.pdf
Nectin-4 New Antibody-Drug Conjugate (ADC) Target.pdf
 

Recently uploaded

What is paper chromatography, principal, procedure,types, diagram, advantages...
What is paper chromatography, principal, procedure,types, diagram, advantages...What is paper chromatography, principal, procedure,types, diagram, advantages...
What is paper chromatography, principal, procedure,types, diagram, advantages...
srcw2322l101
 
Obat Aborsi Pasuruan 0851\7696\3835 Jual Obat Cytotec Di Pasuruan
Obat Aborsi Pasuruan 0851\7696\3835 Jual Obat Cytotec Di PasuruanObat Aborsi Pasuruan 0851\7696\3835 Jual Obat Cytotec Di Pasuruan
Obat Aborsi Pasuruan 0851\7696\3835 Jual Obat Cytotec Di Pasuruan
Obat Aborsi Jakarta Wa 085176963835 Apotek Jual Obat Cytotec Di Jakarta
 
00971508021841 حبوب الإجهاض في دبي | أبوظبي | الشارقة | السطوة |❇ ❈ ((![© ر
00971508021841 حبوب الإجهاض في دبي | أبوظبي | الشارقة | السطوة |❇ ❈ ((![©  ر00971508021841 حبوب الإجهاض في دبي | أبوظبي | الشارقة | السطوة |❇ ❈ ((![©  ر
00971508021841 حبوب الإجهاض في دبي | أبوظبي | الشارقة | السطوة |❇ ❈ ((![© ر
nafizanafzal
 
Obat Aborsi Depok 0851\7696\3835 Jual Obat Cytotec Di Depok
Obat Aborsi Depok 0851\7696\3835 Jual Obat Cytotec Di DepokObat Aborsi Depok 0851\7696\3835 Jual Obat Cytotec Di Depok
Obat Aborsi Depok 0851\7696\3835 Jual Obat Cytotec Di Depok
Obat Aborsi Jakarta Wa 085176963835 Apotek Jual Obat Cytotec Di Jakarta
 
Shots fired Budget Presentation.pdf12312
Shots fired Budget Presentation.pdf12312Shots fired Budget Presentation.pdf12312
Shots fired Budget Presentation.pdf12312
LR1709MUSIC
 
Obat Aborsi Surabaya 0851\7696\3835 Jual Obat Cytotec Di Surabaya
Obat Aborsi Surabaya 0851\7696\3835 Jual Obat Cytotec Di SurabayaObat Aborsi Surabaya 0851\7696\3835 Jual Obat Cytotec Di Surabaya
Obat Aborsi Surabaya 0851\7696\3835 Jual Obat Cytotec Di Surabaya
Obat Aborsi Jakarta Wa 085176963835 Apotek Jual Obat Cytotec Di Jakarta
 
Abortion pills in Muscut<Oman(+27737758557) Cytotec available.inn Kuwait City.
Abortion pills in Muscut<Oman(+27737758557) Cytotec available.inn Kuwait City.Abortion pills in Muscut<Oman(+27737758557) Cytotec available.inn Kuwait City.
Abortion pills in Muscut<Oman(+27737758557) Cytotec available.inn Kuwait City.
daisycvs
 

Recently uploaded (20)

Progress Report - UKG Analyst Summit 2024 - A lot to do - Good Progress1-1.pdf
Progress Report - UKG Analyst Summit 2024 - A lot to do - Good Progress1-1.pdfProgress Report - UKG Analyst Summit 2024 - A lot to do - Good Progress1-1.pdf
Progress Report - UKG Analyst Summit 2024 - A lot to do - Good Progress1-1.pdf
 
Space Tech Expo Exhibitor List 2024 - Exhibitors Data
Space Tech Expo Exhibitor List 2024 - Exhibitors DataSpace Tech Expo Exhibitor List 2024 - Exhibitors Data
Space Tech Expo Exhibitor List 2024 - Exhibitors Data
 
Unlocking Growth The Power of Outsourcing for CPA Firms
Unlocking Growth The Power of Outsourcing for CPA FirmsUnlocking Growth The Power of Outsourcing for CPA Firms
Unlocking Growth The Power of Outsourcing for CPA Firms
 
What is paper chromatography, principal, procedure,types, diagram, advantages...
What is paper chromatography, principal, procedure,types, diagram, advantages...What is paper chromatography, principal, procedure,types, diagram, advantages...
What is paper chromatography, principal, procedure,types, diagram, advantages...
 
Obat Aborsi Pasuruan 0851\7696\3835 Jual Obat Cytotec Di Pasuruan
Obat Aborsi Pasuruan 0851\7696\3835 Jual Obat Cytotec Di PasuruanObat Aborsi Pasuruan 0851\7696\3835 Jual Obat Cytotec Di Pasuruan
Obat Aborsi Pasuruan 0851\7696\3835 Jual Obat Cytotec Di Pasuruan
 
00971508021841 حبوب الإجهاض في دبي | أبوظبي | الشارقة | السطوة |❇ ❈ ((![© ر
00971508021841 حبوب الإجهاض في دبي | أبوظبي | الشارقة | السطوة |❇ ❈ ((![©  ر00971508021841 حبوب الإجهاض في دبي | أبوظبي | الشارقة | السطوة |❇ ❈ ((![©  ر
00971508021841 حبوب الإجهاض في دبي | أبوظبي | الشارقة | السطوة |❇ ❈ ((![© ر
 
Mastering The Art Of 'Closing The Sale'.
Mastering The Art Of 'Closing The Sale'.Mastering The Art Of 'Closing The Sale'.
Mastering The Art Of 'Closing The Sale'.
 
Obat Aborsi Depok 0851\7696\3835 Jual Obat Cytotec Di Depok
Obat Aborsi Depok 0851\7696\3835 Jual Obat Cytotec Di DepokObat Aborsi Depok 0851\7696\3835 Jual Obat Cytotec Di Depok
Obat Aborsi Depok 0851\7696\3835 Jual Obat Cytotec Di Depok
 
Navigating Tax Season with Confidence Streamlines CPA Firms
Navigating Tax Season with Confidence Streamlines CPA FirmsNavigating Tax Season with Confidence Streamlines CPA Firms
Navigating Tax Season with Confidence Streamlines CPA Firms
 
Top^Clinic ^%[+27785538335__Safe*Women's clinic//Abortion Pills In Harare
Top^Clinic ^%[+27785538335__Safe*Women's clinic//Abortion Pills In HarareTop^Clinic ^%[+27785538335__Safe*Women's clinic//Abortion Pills In Harare
Top^Clinic ^%[+27785538335__Safe*Women's clinic//Abortion Pills In Harare
 
MichaelStarkes_UncutGemsProjectSummary.pdf
MichaelStarkes_UncutGemsProjectSummary.pdfMichaelStarkes_UncutGemsProjectSummary.pdf
MichaelStarkes_UncutGemsProjectSummary.pdf
 
WAM Corporate Presentation May 2024_w.pdf
WAM Corporate Presentation May 2024_w.pdfWAM Corporate Presentation May 2024_w.pdf
WAM Corporate Presentation May 2024_w.pdf
 
What are the differences between an international company, a global company, ...
What are the differences between an international company, a global company, ...What are the differences between an international company, a global company, ...
What are the differences between an international company, a global company, ...
 
hyundai capital 2023 consolidated financial statements
hyundai capital 2023 consolidated financial statementshyundai capital 2023 consolidated financial statements
hyundai capital 2023 consolidated financial statements
 
Shots fired Budget Presentation.pdf12312
Shots fired Budget Presentation.pdf12312Shots fired Budget Presentation.pdf12312
Shots fired Budget Presentation.pdf12312
 
Obat Aborsi Surabaya 0851\7696\3835 Jual Obat Cytotec Di Surabaya
Obat Aborsi Surabaya 0851\7696\3835 Jual Obat Cytotec Di SurabayaObat Aborsi Surabaya 0851\7696\3835 Jual Obat Cytotec Di Surabaya
Obat Aborsi Surabaya 0851\7696\3835 Jual Obat Cytotec Di Surabaya
 
Should Law Firms Outsource their Bookkeeping
Should Law Firms Outsource their BookkeepingShould Law Firms Outsource their Bookkeeping
Should Law Firms Outsource their Bookkeeping
 
First Time Home Buyer's Guide - KM Realty Group LLC
First Time Home Buyer's Guide - KM Realty Group LLCFirst Time Home Buyer's Guide - KM Realty Group LLC
First Time Home Buyer's Guide - KM Realty Group LLC
 
Elevate Your Online Presence with SEO Services
Elevate Your Online Presence with SEO ServicesElevate Your Online Presence with SEO Services
Elevate Your Online Presence with SEO Services
 
Abortion pills in Muscut<Oman(+27737758557) Cytotec available.inn Kuwait City.
Abortion pills in Muscut<Oman(+27737758557) Cytotec available.inn Kuwait City.Abortion pills in Muscut<Oman(+27737758557) Cytotec available.inn Kuwait City.
Abortion pills in Muscut<Oman(+27737758557) Cytotec available.inn Kuwait City.
 

Overview of Oral Delivery Strategies for Peptides.pdf

  • 1. Huateng Pharma https://us.huatengsci.com Overview of Oral Delivery Strategies for Peptides Peptides are short chains of amino acids linked by peptide bonds. Compared with traditional small molecule drugs, peptide drugs are featured with strong drugability, high activity, high specificity, low toxicity, and no drug-drug interactions; compared with protein drugs, peptide drugs have the advantages of lower production cost, simpler R&D, and no immunogenicity. Therefore, since the discovery of insulin in 1920, peptide drugs have received increasing attention. Currently, more than 100 peptide drugs have been approved for marketing, with clinical applications covering metabolic diseases, cancer, neurological diseases, immune diseases, etc. Although peptide drugs have a promising therapeutic future, they also have certain drawbacks. The presence of peptidases results in peptide drugs usually having a short half-life, and this instability affects drug development and efficacy. Problems such as low oral efficiency and poor cellular uptake can also affect late-stage drug formation. Oral administration is gradually becoming a research focus as a safe and compliant route of drug delivery. In recent years, research on enhancing the oral absorption of peptides has made great progress in both preclinical and clinical trials. In 2019, the approval of oral semaglutide, developed by Novo Nordisk and Emisphere Technologies, became a major milestone in the field of oral peptides. Strategies for oral delivery of proteins peptides Since the discovery of insulin in 1920, oral peptide research has never stopped, and more than 20 strategies for delivering peptides orally have been reported. As shown in Figure 1, they include enteric coating, pH modulators, enzyme inhibitors; PEGylation, cyclization, prodrugs; mucosal adsorption, microneedling; absorption enhancers, nanotechnology and so on. Among them, the main delivery strategies to get industrial translation are chemical modifications, pH modulators/enzyme inhibitors, permeation enhancers, and SNEDDS.
  • 2. Huateng Pharma https://us.huatengsci.com Figure 1. Strategic approaches for oral delivery of peptides source: reference [1] Chemical Modifications Chemical modifications, which are mainly aimed at improving the half-life of peptides, include PEGylation (polyethylene glycol), glycosylation, lipidation, and using adjuvant molecules to enhance delivery. Among these, the combination of PEG with peptides improves thermal stability, resists protease degradation, reduces antigenicity, and prolongs half-life in vivo. In addition to PEG, lipidation and glycosylation of peptide drugs can also improve the enzyme stability of peptides and so on. For example, by fatty acid acylation of the lysine in position 26, semaglutide improves efficacy, enhances resistance to enzymatic degradation, improves plasma stability, and significantly prolongs half-life. Note: Huateng Pharma provides high quality PEG derivatives for your PEGylation of peptide.
  • 3. Huateng Pharma https://us.huatengsci.com Figure 2. semaglutide structure In addition, cyclic peptides are also one of the key areas of oral peptide research. Peptide cyclization is used to make peptides insensitive to hydrolases by removing the exposed C- and N-terminals from the peptide molecule. In addition, cyclization reduces the exposure of polar atoms to the surrounding environment by folding the peptide into a biologically active conformation, thereby improving the stability and bioavailability of the peptide for oral administration. Although chemical modification of peptides has been extensively studied, it remains a challenge in terms of its industrial feasibility and high cost. pH modulation/Enteric Coating The pH environment of the GI tract leads to the hydrolysis and conformational changes of peptides, as well as their enzymatic degradation at that pH. It has been shown that peptides are relatively stable only in a narrow pH range similar to their isoelectric point. The activity of GI enzymes is closely related to their pH environment. For example, pepsin can only degrade peptides in an acidic environment, , however, pepsin starts to lose their effect when the pH is over 3. In the development strategy for oral semaglutide (Rybelsus®), one of the roles of the excipient SNAC is to raise the local intragastric pH to protect semaglutide from degradation by pepsin. For octreotide (Mycapssa®), enteric coating was used directly to avoid octreotide release in the stomach. In addition, Tarsa Therapeutics (Philadelphia, USA) has successfully completed a phase III trial for oral delivery of sCT (ORACAL) which comprises of an enteric coated capsule to bypass the stomach and citric acid to modulate the pH microenvironment in intestine.
  • 4. Huateng Pharma https://us.huatengsci.com Figure 3. SNAC Technology, source: Novo Nordisk official website Absorption enhancers The addition of absorption enhancers to drug prescriptions is one of the commonly used means of oral formulation. Since a study in 1961 found that EDTA improved the oral absorption of heparin in dogs, absorption enhancers have received a lot of attention in pharmaceutical and biomaterials science. With the rapid development of these disciplines, excipients with better safety and better absorption-promoting effects are emerging. Absorption enhancers can be categorized according to their role as paracellular enhancers, transcellular enhancers, and both paracellular and transcellular enhancers. There are tight junctions, adhesion junctions and desmosome junctions between cells, and these complexes maintain the morphology and integrity of the intestinal wall structure, preventing the passage of bacteria, and undigested proteins through the cellular interstitial space. Chelating agents can reduce Ca2+ concentration by chelating with extracellular Ca2+, which in turn leads to an increase in cellular paracellular permeability through a series of signaling pathways; the effect is reversible, and cellular permeability recovers after an increase in Ca2+ concentration. Commonly used chelating agents include EDTA, citric acid, etc. Oramed Pharma uses EDTA as absorption enhancers, and clinical studies have shown that the oral relative bioavailability of insulin in the group employing EDTA was 20% higher when compared to chitosan nanoparticles of insulin. Most surfactants, including sodium caprylate and their derivatives, and bile salts, are commonly used transcellular absorption enhancers, which make drugs more accessible to cells by increasing the permeability of cell membranes or increasing the lipophilicity of the drug. For example, one of the reasons why SNAC, an excipient in oral semaglutide prescription, enhances
  • 5. Huateng Pharma https://us.huatengsci.com absorption is that it promotes the monomerization of semaglutide and its interaction with the plasma membrane, thus increasing its permeability. Oral bioavailability has also been enhanced by the use of 5-CNAC in a clinical-stage sCT (SMC021), which is in phase III clinical trials. In addition, such as sodium decanoate, sodium octanoate also has the effect of enhancing both paracellular and transcellular absorption. Sodium decanoate can increase intracellular Ca2+ concentration, phosphorylate myosin light chain after signaling to open cellular paracellular pathway, and also has the effect of disturbing the plasma membrane to enhance intestinal permeability. SNEDDS Self-nanoemulsifying drug delivery systems (SNEDDS) were regarded as an important strategy for improving oral absorption of drug molecules. Among the marketed products, cyclosporin A (Neoral® and Sandimmune®), as well as Voclosporin (wupkynis®) employ SNEDDS technology. SNEDDS is a lipid-based drug delivery system in which the formulation consists mainly of an oil phase, a surfactant and a co-surfactant. After oral administration, the self-microemulsions spontaneously and rapidly form O/W type drug-carrying microemulsions in the gastrointestinal fluid under gastrointestinal peristalsis, with droplet sizes <100 nm. The droplets formed in the gastrointestinal tract are small in size and widely distributed, which improves the concentration of difficult-to-solve drugs in the gastrointestinal tract and promotes osmotic transmembrane absorption. During the process of emulsion breaking and digestion, the fatty acids digested from the core oil, the bile acid salts secreted in the body and the phospholipids in the food can form mixed micelles, which wraps the raw materials into the micelles, thus promoting the absorption of the raw materials by the osmotic, transporter, cytosolic and lymphatic pathways. Some lipid excipients such as C8 octanoic acid oil, C10 decanoic acid derivatives also have a certain degree of pro-absorption effect. However, it should be noted that Voclosporin is essentially a structural analog of cyclosporin A, and both are water-insoluble and lipophilic drugs. SNEDDS is not suitable for drugs with strong water solubility, and at the same time, for drugs with poor hydrophilic and lipophilic properties, there is a possibility that the drug may be heavily enriched in the interfacial layer after the formation of the microemulsion, leading to precipitation or degradation. Overview of The Current Clinical Studies Cyclosporin A (Sandimmune®), a cyclic peptide with a molecular weight of 1202, was the first FDA-approved oral peptide. 5 years later, Novartis developed and approved Neoral®, a modified version of cyclosporin A. In 2019,
  • 6. Huateng Pharma https://us.huatengsci.com an oral formulation of semaglutide, developed by Novo Nordisk, was approved by the FDA for the treatment of type II diabetes mellitus. Octreotide extended-release capsules (Mycapssa®) were approved for marketing by the FDA in 2020. These last two oral peptide products are revolutionizing the field of oral peptides. There are currently 17 oral peptide drugs successfully marketed worldwide, of which 8 are absorbed into the bloodstream after oral administration. Table. Marketed oral peptide Conslusion We provide an overview of the current landscape of oral peptides in marketing and clinical studies, a review of the forms of delivery used, and a summary and analysis of the common strategies used for oral peptides that have been successfully translated into industry. In fact, each successfully marketed oral peptide may include a combination of different absorption enhancing strategies, such as octreotide (Mycapssa®), which uses both absorption enhancers and enteric coating technology, somatostatin (Rybelsus®), which has an optimized chemical structure, and excipient SNAC, which acts as both a pH modulator and an absorption enhancer. With the emergence of more oral peptides and the availability of new functional excipients, oral peptide delivery technologies capable of overcoming human physiological barriers will continue to emerge, facilitating the wider clinical application of peptides. Huateng Pharma is known worldwide for a variety of pharmaceutical intermediates used in research and development. We can provide antidiabetic drug intermediates such as semaglutide intermediates, liraglutide
  • 7. Huateng Pharma https://us.huatengsci.com intermediates, canagliflozin intermediates, dapagliflozin intermediates and em pagliflozin intermediates for your research. We have our own factory and make scale-up production with capacities varying from gram to kilograms and multi tons. References: 1. Zhu, Quangang & Chen, Zhongjian & Paul, Pijush & Lu, Yi & Wu, Wei & Qi, Jianping. (2021). Oral delivery of proteins and peptides: Challenges, status quo and future perspectives. Acta Pharmaceutica Sinica B. 11. 2417-2449. 10.1016/j.apsb.2021.04.001. 2. Su FY, Lin KJ, Sonaje K, Wey SP, Yen TC, Ho YC, et al. Protease inhibition and absorption enhancement by functional nanoparticles for effective oral insulin delivery. Biomaterials., 2012, 33:2801. 3. Pandya AK, Patravale VB. Computational avenues in oral protein and peptide therapeutics. Drug Discov Today. 2021;26(6):1510-1520. doi:10.1016/j.drudis.2021.03.003 4. Drucker DJ. Advances in oral peptide therapeutics. Nat RevDrug Discov. 2019 Dec 17. doi: 10.1038/s41573-019-0053-0.