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Oral Delivery Of Therapeutic Proteins And Peptides: A Review On Recent Developments
S. Gupta, Arushi Jain, M. Chakraborty, J. Sahni, J. Ali, Shweta Dang
Published 2013 · Medicine
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Abstract Advent of recombinant technology in protein synthesis has given birth to a new range of biopharmaceuticals. These therapeutic peptides and proteins are now emerging as an imperative part of various treatment protocols especially in the cancer therapeutics. Despite extensive research efforts, oral delivery of therapeutic peptide or protein is still a challenge for pharmaceutical industries and researchers. Number of factors including high proteolytic activity and low pH conditions of gastrointestinal tract act as major barriers in the successful delivery of intact protein/peptide to the targeted site. Low permeability of protein/peptide across the intestinal barrier is also a factor adding to the low bioavailability. Therefore, because of the short circulatory half-life exhibited by peptides in vivo, they need to be administered frequently resulting in increased cost of treatment and low patient compliance. Nano-carrier-based delivery presents an appropriate choice of drug carriers owing to their property to protect proteins from degradation by the low pH conditions in stomach or by the proteolytic enzymes in the gastrointestinal tract. This review focuses on recent aspects and patents on oral delivery of therapeutic proteins and peptides with special emphasis on nano-carrier-based approach.
This paper references
Oral delivery system for two-pulse colonic release of protein drugs and protease inhibitor/absorption enhancer compounds.
M. D. Del Curto (2011)
Protein encapsulation and release from poly(lactide-co-glycolide) microspheres: effect of the protein and polymer properties and of the co-encapsulation of surfactants.
D. Blanco (1998)
Distribution of thiolated mucoadhesive nanoparticles on intestinal mucosa.
S. Dünnhaupt (2011)
inventor; The Regents of the University of California, assignee. Particles for oral delivery of peptides and protein
M Ferrari (2002)
inventors; The Board of Trustees of the University of Illinois, assignee. Surface modified protein microparticles
KS Suslick (2007)
Oral formulation for gastrointestinal drug delivery
Insulin-cell penetrating peptide hybrids with improved intestinal absorption efficiency.
J. Liang (2005)
Preparation and characterization of salmon calcitonin-sodium triphosphate ionic complex for oral delivery.
H. E. Lee (2010)
Preparation and evaluation of alginate-chitosan microspheres for oral delivery of insulin.
Y. Zhang (2011)
Lyophilization of water-in-oil emulsions to prepare phospholipid-based anhydrous reverse micelles for oral peptide delivery.
Ting Wang (2010)
Nanostructured porous silicon microparticles enable sustained peptide (Melanotan II) delivery.
M. Kilpeläinen (2011)
inventor; Oshadi Drug Administration Ltd., assignee. Methods and composition for oral administration of protein and peptide therapeutic agents. World Intellectual Property Organization WO2009087633
A Vol (2009)
Marks DL, inventors; The Board of Trustees of the University of Illinois, assignee. Surface modified protein microparticles. United States patent US 7217410
K S Suslick
A mucoadhesive nanoparticulate system for the simultaneous delivery of macromolecules and permeation enhancers to the intestinal mucosa.
Abdallah Makhlof (2011)
inventor; Ores Pharmaceutical Development Corp., assignee. Polymer composition for oral administration of peptides and proteins. European Patent EP 0918543
N A Plate
Significant systemic and mucosal immune response induced on oral delivery of diphtheria toxoid using nano‐bilosomes
A. Shukla (2011)
Self-double-emulsifying drug delivery system (SDEDDS): a new way for oral delivery of drugs with high solubility and low permeability.
X. Qi (2011)
Polymeric nanoparticles for drug delivery.
J. M. Chan (2010)
The University of Cincinnati, assignee. Oral administration of therapeutic proteins. United States patent US 6613332
J C Michael
Investigation of archaeosomes as carriers for oral delivery of peptides.
Z. Li (2010)
Enhancing effect of chitosan on peptide drug delivery across buccal mucosa.
S. Şenel (2000)
Synthesis and evaluation of lauryl succinyl chitosan particles towards oral insulin delivery and absorption.
M. Rekha (2009)
Review on Microparticulate Drug Delivery System
N. V. S. Madhav (2011)
Design and evaluation of novel pH-sensitive chitosan nanoparticles for oral insulin delivery.
Abdallah Makhlof (2011)
Fatty acid formulations for oral delivery of proteins and peptides, and uses thereof. United States patent 7605123
B Radhakrishnan (2009)
inventor; Ores Pharmaceutical Development Corp., assignee. Polymer composition for oral administration of peptides and proteins
NA Plate (2004)
A comparative study of chitosan and chitosan/cyclodextrin nanoparticles as potential carriers for the oral delivery of small peptides.
A. Trapani (2010)
In vitro evaluation of N-(2-hydroxy) propyl-3-trimethyl ammonium chitosan for oral insulin delivery
T. A. Sonia (2011)
inventor; Cima Labs Inc., assignee. Microemulsions as solid dosage forms for oral administration. United States patent 6280770
S I Pather
Bioadhesives for optimization of drug delivery.
N. Peppas (1995)
Liposomes in drug delivery: Progress and limitations
Amarnath Sharma (1997)
inventor; The University of Cincinnati, assignee. Oral administration of therapeutic proteins
JC Michael (2003)
Transcytosis of nanoparticle and dendrimer delivery systems: evolving vistas.
A. Florence (2001)
Design of poly(ethylene glycol)-tethered copolymers as novel mucoadhesive drug delivery systems.
Laura Serra (2006)
Drug permeability and mucoadhesion properties of thiolated trimethyl chitosan nanoparticles in oral insulin delivery.
Lichen Yin (2009)
Chitosan-aprotinin coated liposomes for oral peptide delivery: Development, characterisation and in vivo evaluation.
M. Werle (2009)
Drug-loaded nanocarriers: passive targeting and crossing of biological barriers.
J. Rabanel (2012)
Utilizing Bacterial Mechanisms of Epithelial Cell Entry: Invasin-induced Oral Uptake of Latex Nanoparticles
N. Hussain (2004)
Carbopol/Chitosan Based pH Triggered In Situ Gelling System for Ocular Delivery of Timolol Maleate
S. Gupta (2010)
A polymeric composite carrier for oral delivery of peptide drugs: Bilaminated hydrogel film loaded with nanoparticles
Chunbai He (2009)
Release and bioactivity of PACA nanoparticles containing D-Lys⁶-GnRH for brushtail possum fertility control.
Alexandra P Kafka (2011)
Polyanionic carbohydrate doxorubicin–dextran nanocomplex as a delivery system for anticancer drugs: in vitro analysis and evaluations
P. Yousefpour (2011)
The influence of polymer architecture on the protective effect of novel comb shaped amphiphilic poly(allylamine) against in vitro enzymatic degradation of insulin--towards oral insulin delivery.
C. Thompson (2010)
In vivo protein transduction: delivery of a biologically active protein into the mouse.
S. Schwarze (1999)
Oral Delivery of Proteins and Peptides: Concepts and Applications
Gaurang Patel (2011)
Oshadi Drug Administration Ltd., assignee. Methods and composition for oral administration of protein and peptide therapeutic agents. World Intellectual Property Organization WO2009087633
inventor; Technion Research and Development Foundation Ltd., assignee. Oral delivery of proteins and peptides. World Intellectual Property Organization WO
Preparations, characterizations and applications of chitosan-based nanoparticles
Chenguang Liu (2007)
inventor; Research Corporation, assignee. Orally administered biologically active peptides and proteins
LL Teng (1986)
inventor; Technion Research and Development Foundation Ltd., assignee. Oral delivery of proteins and peptides
E Shimoni (2008)
Penetration enhancer sand ocular bioadhesives: two new avenues for ophthalmic drug delivery
IP Kaur (2002)
Research Corporation, assignee. Orally administered biologically active peptides and proteins. United States patent US 4582820
L L Teng
Exploring novel approaches to vaginal drug delivery.
S. Gupta (2011)
inventor; Kirin-Amgen, Inc., assignee. Oral dosage form of biologically active proteins
H Nomura (1997)
Biodegradable alginate microparticles developed by electrohydrodynamic spraying techniques for oral delivery of protein
Tittaya Suksamran (2009)
Chitosan–glutathione conjugate-coated poly(butyl cyanoacrylate) nanoparticles: Promising carriers for oral thymopentin delivery
Xuefeng Jin (2011)
Oral and pulmonary delivery of thioether-bridged angiotensin-(1–7)
L. D. Vries (2010)
Uptake of drugs into the intestinal lymphatics after oral administration
C. H. Porter (1997)
In vitro and in vivo evaluation of WGA-carbopol modified liposomes as carriers for oral peptide delivery.
Abdallah Makhlof (2011)
Oral dosage form of biologically active proteins. United States patent US 5597562
Biocon Ltd., assignee. Fatty acid formulations for oral delivery of proteins and peptides, and uses thereof. United States patent 7605123
Oral biodrug delivery using cell-penetrating peptide.
E. Khafagy (2012)
Penetration Enhancers and Ocular Bioadhesives: Two New Avenues for Ophthalmic Drug Delivery
I. P. Kaur (2002)
Magnetically Responsive Polymeric Microparticles for Oral Delivery of Protein Drugs
J. Cheng (2005)
Efficacy, safety and mechanism of cyclodextrins as absorption enhancers in nasal delivery of peptide and protein drugs.
E. Marttin (1998)
inventor; The Regents of the University of California, assignee. Particles for oral delivery of peptides and protein. United States patent US 6355270
The complexation between novel comb shaped amphiphilic polyallylamine and insulin: towards oral insulin delivery.
C. Thompson (2009)
Mucoadhesive drug delivery systems
Rahamatullah Shaikh (2011)
Developments and applications of cyanoacrylate adhesives
K. Shantha (1989)
In vitro and in vivo characterisation of a novel peptide delivery system: amphiphilic polyelectrolyte-salmon calcitonin nanocomplexes.
Woei-Ping Cheng (2010)
Enhanced Mucoadhesive Capacity of Novel Co-polymers for Oral Protein Delivery
F. Marks (2011)
Alkermes Controlled Therapeutics, Inc., assignee. Protein microspheres and methods of using them. United States patent US 5679377
H Bernstein (1997)
This paper is referenced by
Goblet cell targeting nanoparticle containing drug-loaded micelle cores for oral delivery of insulin.
P. Zhang (2015)
Position Paper : Fertility intervention and toxicant technologies for the eradication of rodents on Lord Howe Island
A. Swegen (2017)
Capsosomes as Long-Term Delivery Vehicles for Protein Therapeutics.
J. Maina (2015)
Thoughts on the progression of type 2 diabetes drug discovery
Harikrashna Bhatt (2015)
Genetically Encoded Cyclic Peptide Libraries: From Hit to Lead and Beyond.
Jacob Valentine (2018)
Formulation technologies and advances for oral delivery of novel nitroimidazoles and antimicrobial peptides.
John Ndayishimiye (2020)
Nanocarrier for Oral Peptide Delivery Produced by Polyelectrolyte Complexation in Nanoconfinement.
W. He (2015)
Scalable Production of Therapeutic Protein Nanoparticles Using Flash Nanoprecipitation.
Z. Zeng (2019)
Release pattern of dexamethasone after administration through an implant-mediated drug delivery device with an active plunger of super absorbent polymer
S. Yang (2018)
Injectable In Situ-Forming Hydrogels for Protein and Peptide Delivery.
Seung Hun Park (2020)
Novel TREM-1 Inhibitors Attenuate Tumor Growth and Prolong Survival in Experimental Pancreatic Cancer.
Z. Shen (2017)
The impact of nanoparticles on the mucosal translocation and transport of GLP-1 across the intestinal epithelium.
F. Araújo (2014)
Microfluidic Assembly of a Multifunctional Tailorable Composite System Designed for Site Specific Combined Oral Delivery of Peptide Drugs.
F. Araújo (2015)
Influence of Molecular Weight and Degree of Deacetylation of Low Molecular Weight Chitosan on the Bioactivity of Oral Insulin Preparations
N. Qinna (2015)
Protein-loaded emulsion electrospun fibers optimized for bioactivity retention and pH-controlled release for peroral delivery of biologic therapeutics.
H. Frizzell (2017)
Understanding enzymatic acceleration at nanoparticle interfaces: Approaches and challenges
Brandy J. Johnson (2014)
Direct solid-phase peptide synthesis on chitosan microparticles for targeting tumor cells
I. Meerovich (2019)
Development of a Drug Delivery System Based on Chitosan Nanoparticles for Oral Administration of Interferon-α.
Camila Cánepa (2017)
Contraception and immunocastration vaccines. Use in veterinary medicine
Ana Cristina Campal-Espinosa (2020)
A novel ligand-independent peptide inhibitor of TREM-1 suppresses tumor growth in human lung cancer xenografts and prolongs survival of mice with lipopolysaccharide-induced septic shock.
A. Sigalov (2014)
Functionalized Graphene Oxide with Chitosan for Protein Nanocarriers to Protect against Enzymatic Cleavage and Retain Collagenase Activity
Fatemeh Emadi (2017)
Potential of single cationic amino acid molecule "Arginine" for stimulating oral absorption of insulin.
N. Kamei (2017)
Conjugation of a nonspecific antiviral sapogenin with a specific HIV fusion inhibitor: a promising strategy for discovering new antiviral therapeutics.
Chao Wang (2014)
Silica nanoparticles: A promising platform for enhanced oral delivery of macromolecules.
Muhammad Mustafa Abeer (2020)
Synthesis of a nanoparticle system for theenhanced accumulation of fluorescently-labelledamino acids encapsulated in monodispersedchitosan nanoparticle system
U. A. Hassan (2017)
High-throughput in vitro drug release and pharmacokinetic simulation as a tool for drug delivery system development: application to intravitreal ocular administration.
S. Sarkhel (2014)
Influence of physiological and chemical factors on the absorption of bioactive peptides
M. Karaś (2019)
Development of METx : a vasopressin agonist
S. Patel (2017)
Preparation of hollow porous silica nanospheres and their potential for glucagon-like peptide-1 delivery
B. Cho (2019)
SARS Coronavirus Fusion Peptide-Derived Sequence Suppresses Collagen-Induced Arthritis in DBA/1J Mice
Z. Shen (2016)
Oral DhHP-6 for the Treatment of Type 2 Diabetes Mellitus
K. Wang (2019)
Binary and Tertiary Complex Based on Short-Chain Glucan and Proanthocyanidins for Oral Insulin Delivery.
N. Ji (2017)See more