Recent trends in protein and peptide drug delivery systems

Main Article Content

Himanshu Gupta
Aarti Sharma


With the discovery of insulin in 1922, identification and commercialization of potential protein and peptide drugs have been increased. Since then, research and development to improve the means of delivering protein therapeutics
to patients has begun. The research efforts have followed two basic pathways: One path focused on noninvasive means of delivering proteins to the body and the second path has been primarily aimed at increasing the biological half-life of the
therapeutic molecules.The search for approaches that provide formulations that are stable, bioavailable, readily manufacturable, and acceptable to the patient, has led to major advances in the development of nasal and controlled release technology, applicable to every protein or peptide. In several limited cases, sustained delivery of peptides and proteins has employed
the use of polymeric carriers. More successes have been achieved by chemical modification using amino acid substitutions, protein pegylation or glycosylation to improve the pharmacodynamic properties of certain macromolecules and various
delivery systems have been developed like the prolease technology, nano-particulate and microparticulate delivery systems, and the mucoadhesive delivery of peptides. The needle and syringe remain the primary means of protein delivery. Major hurdles remain in order to overcome the combined natural barriers of drug permeability, drug stability, pharmacokinetics, and pharmacodynamics of protein therapeutics. In our present review we have tried to compile some recent advances in protein and peptide drug delivery systems.


Download data is not yet available.

Article Details

How to Cite
Gupta, H., & Sharma, A. (2014). Recent trends in protein and peptide drug delivery systems. Asian Journal of Pharmaceutics (AJP), 3(2).


Semalty A, Semalty M, Singh R, Saraf SK, Shubhini S. properties and

formulation of Oral Drug Delivery Systems of Protein and Peptides. Indian

Journal of Pharmaceutical Sciences 2007;69:741-7.

Matthews DM. Intestinal absorption of peptides. Physiol Rev


Dence JE. Steroids and Peptide: Selected Chemical Aspects for Biology.

Biochemistry and medicine 1980;89.

Nelson DL, Cox MM. Lehninger Principles of Biochemistry. 4th ed.,

New York: W.H. Freeman and Company: 2005. p. 85-6.

McMartin C, Hutchinson LE, Hyde R, Peters GE. Analysis of structural

requirements for the absorption of drugs and macromolecules from

the nasal cavity. J Pharm Sci 1987;76:535-40.

Donovan MD, Flynn GL, Amidon GL. Asorption of polyethylene glycols

through 2000: The Molecular dependence of gastrointestinal and

nasal absorption. Pharm Res 1990:7:863-8.

Maitani Y, Machida Y, Nagai T. Influence of molecular weight and charge

on nasal absorption of dextran and DEAE-dextran in rabbits. Int j Pharm


Roberts MJ, Bentley MD, Harris JM. Chemistry for peptide and protein

PEGylation. Adv Drug Del Rev 2002;54:459-76.

Mateo C, Lombardero J, Moreno E, Morales A, Bombino G, Coloma J,

et al. Removal of amphipathic epitopes from genetically engineered

antibodies: Production of modified immmunoglobulins with reduced

immunogenicity. Hybridoma 2000;19:436-71.

Lyczak JB, Morrison SL. Biological and pharmacokinetic properties of a

novel immunoglobulin-CD4 fusion protein. Arch Virol 1994;139:189-96.

Syed S, Schuyler PD, Kulczycky M, Sheffield WP. Potent antithrombin

activity and delayed clearance from the circulation characterize

recombinant hirudin genetically fused to albumin. Blood 1997;89:3242-52.

Bot AI, Tarara TE, Smith DJ, Bot SR, Woods CM, Weers JG. Novel lipid-

based hollow-porous microparticles as a platform for immunoglobulin

delivery to the respiratory tract. Pharm Res 2000;17:275-83.

Hutchinson FG, Furr BJ. Biodegradable polymers for controlled Particle

characteristics and lung deposition patterns in a human airway replica of

a dry powder formulation of polylactic acid produced using supercritical

fluid technology. J Aerosol Med 2003;16:65-73.

Padmanabhan RV, Gudapaty R, Liener IE, Schwartz BA, Hoidal JR.

Protection against pulmonary oxygen toxicity in rats by the intratracheal

administration of liposome-encapsulated superoxide dismutase or

catalase. Am Rev Respir Dis 1985;132:164-7.

Wagner A, Vorauer-Uhl K, Kreismayr G, Katinger H. Enhanced protein

loading into liposomes by the multiple crossflow injection technique.

J Liposome Res 2002;12:271-83.

Colletier JP, Chaize B, Winterhalter M, Fournier D. Protein encapsulation

in liposomes: Efficiency depends on interactions between protein and

phospholipid bilayer. BMC Biotechnol 2002;2:9.

Crommelin D, Schreier H. Liposomes. In: Kreuter J, editor. Colloidal

Drug Delivery Systems. New York, NY: Marcel Dekker; 1994. p. 73-190.

Banga A. Therapeutic Peptides and Proteins: Formulation,Processing

and Delivery. Lancaster, PA: Techtomic Publishing Company Inc.; 1995.

Cipolla D, Farr SJ, Gonda I, Otulana B. Delivery of biologics to the lung.

In: Hansel TT, Barnes PJ, editors. New Drugs for Asthma, Allergy and

COPD. Prog. Respir Res Basel. Switzerland: Karger; 2001;31:20-3.

Dokka S, Toledo D, Shi X, Castranova V, Rojanasakul Y. Oxygen radical-mediated pulmonary toxicity induced by some cationic liposomes.

Pharm Res 2000;17:521-5.

Shaji J, Patole V. Protein and Peptide Drug Delivery: Oral Approaches.

Indian Journal of Pharmaceutical Sciences 2008;70:269-77.

Available from: Http:// [last accessed

on 2008 Sep. 19]

Y, Matusushima A, Hiroto M, Nishimura H, Ishii A, Ueno T, Inada Y.

Pegylation of proteins and bioactive substances for medical and

technical applications. Progress in Polymer Science 1998;23:1233-71.

Harris JM, Martin NE, Modi M. Pegylation: A novel Process for Modifying

Pharmacokinetics. Clin Pharmacokinet 2001;40:539-51.

Goodson RJ, Katre NV. Site-directed pegylation of recombinant

interleukin-2 at its glycosylation site. Biotechnology 1990;8:343-6.

Harris JM, Martin NE, Modi M. Pegylation: A novel process for modifying

pharmacokinetics. Clin Pharmacokinet 2001;40:539-51.

Cattel L, Ceruti M, Dosio F. From conventional to stealth liposomes:

A new frontier in cancer chemotherapy. J chemother 2004;16:94-7.

Al-Tabakha MM, Arida AI. Recent Challenges in Insulin Delivery Systems:

A Review. Indian Journal of Pharmaceutical Sciences 2008;70:278-86.

Malik DK, Baboota S, Ahuja A, Hasan S, Ali J. Recent Advances in Protein

and Peptide Drug Delivery Systems. Curr Drug Deliv 2007;4:141-51.

Brown L, Rashba-Step J, Scott T, et al. Pulmonary delivery of novel insulin

microspheres. In: Dalby R, Byron PR, Peart J, Farr SJ, editors. Respiratory

Drug Delivery XIII. Raleigh. NC: Davis Horwood International

Publishing; 2002. p. 431-3.

Fiegel J, Ehrhardt C, Schaefer UF, Lehr CM, Hanes J. Large porous particle

impingement on lung epithelial cell monolayers-toward improved

particle characterization in the lung. Pharm Res 2003;20:788-96.

Evora C, Soriano I, Rogers RA, Shakesheff KN, Hanes J, Langer R. Relating

the phagocytosis of microparticles by alveolar macrophages to surface

chemistry: The effect of 1,2-dipalmitoylphosphatidylcholine. J Control

Release 1998;51:143-52.

Bittner B, Kissel T. Ultrasonic atomization for spray drying: A versatile

technique for the preparation of protein loaded biodegradable

microspheres. J Microencapsul 1999;16:325-41.

Byron PR. Drug delivery devices: Issues in drug development. Proc Am

Thorac Soc. 2004;1:321-8.

Hollander P. Efficacy and safety of inhaled insulin (Exubera®) compared

to sc insulin therapy in patients with type 2 diabetes: Results of a

-month, randomized, comparative trial, for the Exubera phase III study

group. Late-breaking poster for President’s Poster Session presented

at the American Diabetes Association. 61st Scientific Sessions 2001.

Cefalu WT, Balagtas CC, Landschulz WH, Gelfand RA. Sustained efficacy

and pulmonary safety of inhaled insulin during 2-years of outpatient

therapy. Paper (A101) published in the American Diabetes Association’s

Diabetes Abstract Book for the 60th Scientific Sessions. 2000.

Cefalu WT, Skyler JS, Kourides IA, Landschulz WH, Balagtas CC, Cheng S,

et al. Inhaled human insulin treatment in patients with type 2 diabetes

mellitus. Ann Intern Med 2001;134:203-7.

Skyler JS, Cefalu WT, Kourides IA, Landschulz WH, Balagtas CC,

et al. Efficacy of inhaled human insulin in type 1 diabetes mellitus:

A randomized proof-of-concept study. Lancet 2001;357:331-5.

Rosenstock J. Mealtime rapid-acting inhaled insulin (Exubera®) improves

glycemic control in patients with type 2 diabetes failing combination

oral agents: A 3-month, randomized, comparative trial for the Exubera®

phase III study group. Paper (A132) published in the American Diabetes

Association’s Diabetes Abstract Book for the 62nd Scientific Sessions.

Su M, Testa MA, Turner RR, Simonson DC. The relationship between

regimen burden and psychological well being in persons with type I

diabetes: Inhaled vs injectable insulin. Paper (A448) published in the

American Diabetes Association’s Diabetes Abstract Book for the 62nd

Scientific Sessions. 2002.

Cappelleri JC, Gerber RA, Rosenstock J, Nadkami S, Petrie CD, Kourides

IA. Relationship between improved patient satisfaction and improved

glycemic control in patients with type 1 and type 2 diabetes mellitus

treated with inhaled insulin: Pooled results from two multicenter

randomized controlled trials. Paper (A108) published in the American

Diabetes Association’s Diabetes Abstract Book for the 61st Scientific

Sessions. 2001.

Simonson DC, Hayes JF, Turner RR Testa M. Treatment satisfaction and

preferences in type 2 diabetes: A randomized trial of oral agents vs

inhaled insulin. 3-month study included: Patients on oral agents only;

patients on both inhaled and oral agents; patients on inhaled insulin

only (monotherapy). Paper (A131) published in the American Diabetes

Association’s Diabetes Book for the 61st Scientific Sessions. 2001.

Available from: Http://

Rhodes WE. Pulmonary and Nasal Delivery of Protein Drugs: Advanced

Delivery Devices. Drug Delivery Technology 2002;2.

Availabe from: Http://

Feb_1/ai_53672067. [last accessed on 2008 Sep. 19].

Henry RR, Mudaliar SR, Howland WC 3rd, Chu N, Kim D, An B, et al.

Inhaled insulin using the AERx Insulin Diabetes Management System

in healthy and asthmatic subjects. Diabetes Care 2003;26:764-9.

Schuetz YB, Naik A, Guy RH, Kalia YN. Emerging strategies for the

Transdermal delivery of peptide and protein drugs. Expert Opin Drug

Deliv 2005;2:533-48.

Benson HA. Transdermal drug delivery: Penetration enhancement

techniques. Curr Drug Deliv 2005;2:23-33.

Scheindlin S. Transdermal drug delivery: PAST, PRESENT, FUTURE. Mol

Interv 2004;4:308-12.

Amsden BG, Goosen MF. Transdermal delivery of peptide and protein

drugs: An overview. AIChE journal 2004:41:1972-97.

Hadgraft J. Passive enhancement strategies in topical and transdermal

drug delivery. Int J Pharm 1999;184:1-6.

Available from :

pdf [last accessed on 2008 Aug. 24].

Avaialble from:

ntentandtask=viewandid=16andItemid=30 [last accessed on 2008

Aug. 24].

Matriano JA, Cormier M, Johnson J, Young WA, Buttery M, Nyam K,

Daddona PE. Macroflux® microprojection array patch technology: A

new and efficient approach for intracutaneous immunization. Pharm

Res 2002; 19:1963-70.

Lin W, Cormier M, Samiee A, Griffin A, Johnson B, Teng CL, Hardee

GE, Daddona PE. Transdermal delivery of antisense oligonucleotides

with microprojection patch (Macroflux®) technology. Pharm Res


Gonjari I.D.,Kasture P.V, Karmarkar A.B., Solid in situ gelling nasal

formulations: A tool for systemic drug delivery, Pharmaceutical reviews,

, 5(2) Available from: Http://