NON INVASIVE DELIVERY OF PROTEIN AND PEPTIDE DRUGS: A REVIEW


Lakshmi Pk, Prasanthi D, Harini K

Abstract


Till recent, injections remained the most common route for administration of protein and peptide drugs because of their poor bioavailability in the other routes. Because it is generally recognized that injection based delivery is a major impediment to the commercial success of therapeutic proteins and peptides, research in both academia and industry continues to focus on ways to overcome this problem. Possible non-parenteral administration routes for delivery of peptide and protein drugs include oral, nasal, ocular, transdermal, rectal, colonic, and vaginal route. The large surface area associated with most of these routes makes them attractive targets for drug delivery. While non-invasive administration by these routes is considered a more logical and achievable option for local treatment regimens, systemic delivery of proteins and peptides is significantly more challenging. In spite of effort made on the development of drugs for these routes, most of the successes fail to address how the technology will be transformed to a commercial product. The only notable exceptions have been the successful commercialization of nasal formulations for systemic delivery of a limited number of therapeutic peptides, and recent regulatory approvals of both pulmonary and buccal delivery systems for systemic delivery of insulin and an oral formulation of a small peptide analog, cyclosporine, have been commercialized. The present review aims to discuss the potential non-invasive routes of protein and peptide drug delivery. The factors which will affect drug transport and the bioavailability of proteins administered through these routes is also emphasized


Keywords


Protein and peptide, Non-invasive, Oral, Nasal, Rectal, Transdermal, Colonic, Vaginal.

| PDF |

References


Whitehouse PJ, Price DL, Struble RG, Clark AW, Coyle JT, Delon MR. Alzheimer’s disease and senile dementia: Loss of neurons in the basal forebrain. Science 1982;215(4537):1237-9.

Agyilirah GA., Banker GS. Polymers for enteric coating applications, in P.J. Tarcha eds, Polymers for Controlled Drug Delivery. 1991;39–66.

Akira Yamamoto, Shozo Muranishi. Rectal drug delivery systems, Improvement of rectal peptide absorption by absorption enhancers, protease inhibitors and chemical modification. Advanced Drug Delivery Reviews 1997;28(2), 275-299.

Ananta Choudhury, Sujoy Das, Mousumi Kar. A Review on Novelty and Potentiality of Vaginal Drug Delivery. International Journal Pharm Tech Research 2011;3(2),1033-1044.

Anushree Herwadkar, Ajay K Banga. Protein and peptide transdermal delivery. Drug Discovery Today Technologies 2012;9(2),147-154.

Behl CR. Pimplaskar AP. Sileno JD, Romeo VD. Effect of physico-chemical and other factors on systemic nasal drug delivery. Advanced Drug Delivery Reviews 1997;(29), 89-116.

Benziger DP, Edelson J. Absorption from the vagina. Drug Metabolism Reviews 1983; 14, 137-168.

Bhise SB, Yadav AV, Avachat AM, Malayandi R. Bioavailability of intranasal drug delivery system. Asian Journal of Pharmaceutics 2008;2(4),201-215.

Blandau RJ. The female reproductive system. In: R.O. Greep and L. Weiss eds. Histology, McGraw-Hill 1997;761-806.

Brondsted H, Hovgaard L, Simonsen L. Dextran hydrogels for colon-specific drug delivery. IV. Comparative release study of hydrocortisone and prednisolone sodium phosphate, S.T.P. Pharma Sci 1995;5, 65–69.

Cevc G, Blume G, Schatzlein A, Gebauer D, Paul A. The skin, A pathway for systemic treatment with patches and lipid-based agent carriers. Advance Drug Delivery Reviews 1996;18 (3) 349–378.

Cevc G. Transfersomes, liposomes and other lipid suspensions on the skin, permeation enhancement, vesicle penetration, and transdermal drug delivery. Crit. Rev. Ther. Drug Carrier Syst, 1996;13(3–4): 257–388.

Cevc G. Transdermal drug delivery of insulin with ultra-deformable carriers. Clinical Pharmacokinetics 2003;42 (5), 461–474.

Chien YW, Chang SF. Intranasal drug delivery for systemic medications. Crit Rev Ther Drug Carr Syst 1987; 67-194.

Clary-Meinesz CF, Cosson J, Huitorel P, Blaive B. Temperature effect on ciliary beat frequency of human nasal and tracheal ciliated cells. Biol Cell 1992;(76), 335-338.

Corssen G, Alien CR. Acetylcholine: Its significance in controlling ciliary activity of human respiratory epithelium in vitro. J Appl Physiol 1959;14:901-904.

Costantino HR, Illum L, Brandt G, Johnson PH, Quay SC. Intranasal delivery: Physicochemical and therapeutic aspects. Int. J. Pharm 2007;337: 1‐24.

De Boer AG, Van Hoogdalem EJ, Heijligers-Feijen CD, Verhoef J, Breimer D. Rectal absorption enhancement of protein drugs. Journal of Controlled Release 1990;13: 241-246.

Denet AR, Vanbever R, Preat V. Skin electroporation for transdermal and topical delivery. Advanced Drug Delivery Reviews 2004;56 (5),659–674.

Deitmer T, Scheffler R. The effect of different preparations of nasal decongestants on ciliary beat frequency in vitro: Rhinology 1993;31(4):151-153.

Donovan MD, Zhou CS. Drug effects on in vivo nasal clearance in rats. Int J Pharm 1995; 116:77-86.

Edman P, Bjork E, Ryden L. Microspheres as a nasal delivery system for peptide drugs. Journal of Control Release 1992;21:165-172.

Egberts HJ, Koninkx JF, Dijk J, Mouwen JM. Biological and pathobiological aspects of the glycocalyx of the small intestinal epithelium, A review Vet. Q 1984; 6 (4):186–199.

Faraj JA, Hussain A, Aramaki Y, Iseki K, Kagoshima M, Dittert LW. Mechanism of nasal absorption of drugs III. Nasal absorption of leucine enkephalin. J Pharm sci 1994; 79:768-770.

Fu Lu M, Lee D, Carlson R, Subba Rao G, Hui HW, Adjei L, Herrin M, Sundberg D, Hsu L. The effects of formulation variable on iontophoretic transdermal delivery of leuprolide to humans, Drug Dev. Ind. Pharm 1993;19 (13):1557–1571.

Ganapathy V, Leibach FH. Is intestinal peptide transport energized by a proton gradient? American Journal of Physiology 1985;249 (12):G153–G160.

Gibson SAW, Mc Farlan C, Hay S, Macfarlane GT. Significance of microflora in proteolysis in the colon, Appl. Environ. Microbiol 1989;55:679-683.

Green PG. Iontophoretic delivery of peptide drugs. J. Control Release 1996;41 (1):3348.

Grimnes S. Pathways of ionic flow through human skin in vivo. Acta Derm-Venereol (Stockh) 1984;64:93–98.

Hastewell J, Williamson I, Mackay M. Cell biology and active transport processes of the colon. Adv. Drug Deliv.Rev. 1991;7:119-148.

Hee J, Guilerm R. Discussion on smoke and mucociliary transport. Eur J Respir Dis Suppl 1985;66:86-88.

Hogben CA, Tocco DJ, Brodie BB, Schanker LS. On the mechanism of intestinal absorption of drugs. J. Pharmacol. Exp. Ther. 1959;125(4):275-282.

Holst E, Brandberg A. Treatment of bacterial vaginosis in pregnancy with a lactate gel. Scandinavian Journal of Infectious Disease 1990;22(5):625–626.

Hussain AA, Dakkuri A, Itoh S. Nasal absorption of ondansetron in rats: An alternative route of drug delivery.Cancer Chemotherapy Pharmacology 2000;45(5):432-4.

Hussain A, Ahsan F. The vagina as a route for systemic drug delivery. Journal of Control Release 2005;103(2):301-313.

Hybbinette JC, Mercke U. Effect of Para sympathomimetic agonists and antagonists on mucociliary activity. Acta Otolaryngol 1982;93(5-6):465-73.

Illum L, Farraj N, Critvhley H, Davis SS. Nasal administration of gentamycin using novel microsphere delivery system for drugs. Int J Pharm 1988;46:261-265.

Illum L, Farraj N, Fisher A. Hyaluronic acid ester microspheres as a nasal delivery system for insulin. J Control Release 1994;29:133-141.

Johnson LN, Cashman SM, Kumar Singh R. Cell-penetrating peptide for enhanced delivery of nucleic acids and drugs to ocular tissues including retina and cornea, Molecular Therapy 2008;16(1):107–14.

Jitendra, Sharma PK, Sumedha Bansal, and Arunabha Banik. Noninvasive routes of proteins and peptides drug delivery. Indian J Pharm Sci 2011;73(4): 367-375.

Julie L, Richardson and Lisbeth Illum. The vaginal route of peptide and protein drug delivery. Advanced Drug Delivery Reviews 1992;8(2-3):341-366.

Kalia Y, Naik A, Garrison J, Guy RH. Iontophoretic drug delivery, Advanced Drug Delivery Reviews 2004;56 (5):619–658.

Kanthakumar K, Cundell DR, Johnson M, Wills PJ, Taylor GW, Cole PJ. Effect of salmeterol on human nasal epithelial cell ciliary beating: Inhibition of ciliotoxin in pyocyanin. British Journal of Pharmacology 112:493-498.

Kao HD, Traboulsi A, Itoh S, Dittert L, Hussain A. Enhancement of the systemic and CNS specific delivery of L-dopa by the nasal administration of its water soluble prodrug. Pharm Res 2000;17: 978‐984.

Kutchai HC. The gastrointestinal system: Berne R.M, Levy M.N. Physiology, 4th Ed Mosby St. Louis. 1998.

Lindberg S, Khan R, Runer T. The effect of formoterol, a long acting beta (2) -adrenoreceptor agonist on mucociliary activity. Eur J Pharmacol 1995;285:275-280.

Liote H, Zahm JM, Pierrot D, Puchelle E. Role of mucus and cilia in nasal mucociliary clearance in healthy subjects. Am, Rev. Respir. Dis 198;140: 132-136. 47. Loftssonaand T, Jarvinen T. Cyclodextrins in ophthalmic drug delivery. Adv Drug Deliv Rev 1999;36(1):59–79.

Lung MA, Phipps RJ, Wang JC, and Widdicombe. Control of nasal vasculature and airflow resistance in the dog. J Physiol 1984;349:535-551.

Meyer BR, Kreis W, Eschbach J, O’Mara V, Rosen S, Sibalis D. Successful transdermal administration of therapeutic doses of a polypeptide to normal human volunteers. Clinical Pharmacology and Therapeutics 1989;44 (6):607–612.

Mitragotri S, Kost J. Low-frequency sonophoresis: a review. Advanced Drug Delivery Reviews 2004;56 (5):589–601.

Moore JA, Pletcher SA, Ross MJ. Absorption enhancement of growth hormone from the gastrointestinal tract of rats. Int. J. Pharm 1986;34: 35–43.

Morimoto K, Takeeda T, Nakamoto Y, Morisaka K. Effective vaginal absorption of insulin in diabetic rats and rabbits using polyacrylic acid aqueous gel bases. International Journal of Pharmaceutics 1982;12:107–111.

Mullen TL, Muller M, and Van Bruggen JT. Role of solute drag in intestinal transport. Journal of General Physiology 1985;85:347-363.

Nightingale CH, Greene DS, Quintiliani R. Pharmacokinetics and clinical use of cephalosporin antibiotics. J Pharm. Sci 1975;64 (12):1899–1927.

Okada H, Yashiki T, Mima H. Vaginal absorption of a potent luteinizing hormone-releasing hormone analogue (leuprolide) in rats III: Effect of estrous cycle on vaginal absorption of hydrophilic model compounds. Journal of Pharmaceutical Sciences 1983; 72(2): 173–176.

Patel LG, Warrington SJ, and Pearson RM. Propranolol concentrations in plasma after insertion into the vagina. Br. Med. J 1983;287:1247-1248.

Prausnitz MR. Microneedles for transdermal drug delivery. Advanced Drug Delivery Reviews 2004;56 (5):581–587.

Potts RO, Francoeur ML. The influence of stratum corneum morphology on water permeability. Journal of Investigative Dermatology 1991;96:495–499.

Purdon CH, Azzi CG, Zhang J, Smith EW, Maibach HI. Penetration enhancement of transdermal delivery-current permutations and limitations, Critical Reviews in Therapeutic Drug Carrier Systems 2004;21 (2):97–132.

Rekha MR, Chandra PS. Oral delivery of therapeutic protein/peptide for diabetes –future perspectives, International Journal of Pharmaceutics. 2013;440(1): 48-62.

Rubinstein Abraham, Tirosh Boaz, Baluom Muhammad, Nassar Taher, David Ayelet, Radai Raphael, Gliko Kabir Irit, Friedman Michael, The rationale for peptide drug delivery to the colon and the potential of polymeric carriers as effective tools, Journal of controlled release 1997;46:59-73.

Saffran M, Kumar GS, Savariar C, Burnham JC, Williams F, and Neckers DC. A new approach to the oral administration of insulin and other peptide drugs, J Pharm. Sci. 1987;233: 1081-1084.

Saffran M, Bedra C, Kumar S, Neckers DC. Vasopressin: A model for the study of effects of additives on the oral and rectal administration of peptide drugs, J. Pharm. Sci. 1988;77(1):33-38.

Sarlikiotis AW, Betzing J, Wohlschlegel C, Bauer KH. A new method for testing colon targeting drug delivery systems or excipients, Pharm. Pharmacol. Lett. 1992;2: 62-65.

Sayani AP, Chien YW. Systemic delivery of peptides and proteins across absorptive mucosa, Critical Review in Therapeutic Drug Carrier System 1996;13(1-2):85-184.

Scheie HG, and Albert DM. Textbook of Ophthalmology, W.B.Saunders, Philadelphia 1977; 9th Ed.

Shaji J, Patole V. Protein and peptide drug delivery: Oral approaches. IJPS 2008; 70(3): 269-277.

Smith NB. Perspectives on transdermal ultrasound mediated drug delivery, Int. J. Nanomed 2007; 2:585–594.

Stratford RE, Carson LW, Dodda-Kashi S, and Lee VHL. Systemic absorption of ocularly administered enkephalinamide and inulin in the albino rabbit: extent, pathways and vehicle effects, Journal of Pharmaceutical Sciences 1988;77(10):838-842.

Sutton SC, Forbes AE, Cargill R, Hochman JH, LeCluyse EL. Simultaneous in vitro measurement of intestinal tissue permeability and transepithelial electrical resistance (TEER) using sweetana- grass diffusion cells, Pharm. Res 1992;9: 316–319.

Talegonkar S, Mishra PR. Intranasal delivery: An approach to by-pass the blood brain barrier, International Journal of Pharmacology 2004;36(3):140-147.

Tao W. Application of encapsulated cell technology for retinal degenerative diseases, Expert Opinion on Biological Therapy 2006;6(7):717–726.

TenHoor, C.N., Dressman, J.B., (1992). Oral absorption of peptides and proteins. Sciences Technologies Pratigues Pharma Sci. 2 (4):301–312.

Turner NG, Nonato LB. Visualization of stratum corneum and transdermal permeation pathways, In: Potts R.O, Guy R.H ed, Mechanisms of Transdermal Drug Delivery. New York: Marcel Dekker 1997;83:1–40.

Ugwoke MI, Agu RU, Vanbilloen H, Baetens J, Augustijns P, Verbeke N et al. Scintigraphic evaluation in rabbits of nasal drug delivery systems based on carbopol 971P and carboxymethylcellulose, J Control Release 2007;68:207-14.

Ulm EH, Hichens M, Gomez HJ, Till AE, Hand E, Vassil TC, Biollaz J, Brunner HR, and Schelling JL. Enalapril maleate and a lysine analogue (MK-521): Disposition in man, British Journal of Clinical Pharmacology 1982;14:357-366.

Van Den Berg MP, Verhoef JC, Romeijn SG, Merkus MW. Uptake of estradiol progesterone into the CSF following intranasal and intravenous delivery in rats, Eur J Pharm Biopharm 2004;58:131-5.

Verdugo P. Goblet cells secretion and mucogenesis, Annual Review of Physiology 1990;52:157-76.

Wan Po AL, Rogers E, Shepphard M, Scott EM. Delivery system for nonparental vaccines, Advanced Drug Delivery Review 1995;18:101-109.

Wei-chiang Shen. Oral peptide and protein delivery: unfulfilled promises? Elsevier Science Ltd 2003; 8(14):607-608.

Williams AC, Barry BW. Penetration enhancers Advanced Drug Delivery, Review 2004;56(5):603–618.

Wood AJ, Maurer G, Niederberger W, and Beveridge T. Cyclosporine: pharmacokinetics, metabolism and drug interactions, Transplant Proc 1983;15(1):2409-2417.

Yokohama S, Yamashita K, Toguchi H, Takeuchi J, Kitamori N. Absorption of thyrotropin-releasing hormone after oral administration of TRH tartrate monohydrate in the rat, dog and human, J. Pharm. Dyn 1984;7 (2):101–111.

Yoshitomi H, Shizuku Y, Masuda Y, Itakura R, Okamoto S, Tomida H, Nishihata T, Goto S. Evaluation of enteric coated tablet sensitive to pancreatic lipase.II. In vivo evaluation, Biological and Pharmaceutical Bulletein 1983;16(12):1260–1263.




About this article

Title

NON INVASIVE DELIVERY OF PROTEIN AND PEPTIDE DRUGS: A REVIEW

Keywords

Protein and peptide, Non-invasive, Oral, Nasal, Rectal, Transdermal, Colonic, Vaginal.

DOI

10.22159/ajpcr.2017.v10i8.18274

Date

01-08-2017

Additional Links

Manuscript Submission

Journal

Asian Journal of Pharmaceutical and Clinical Research
Vol 10 Issue 8 August 2017 Page: 25-33

Print ISSN

0974-2441

Online ISSN

2455-3891

Statistics

91 Views | 153 Downloads

Authors & Affiliations

Lakshmi Pk
Department of Pharmaceutics, G. Pulla Reddy College of Pharmacy, Mehdipatnam, Hyderabad, Telangana, India.
India

Prasanthi D
Department of Pharmaceutics, G. Pulla Reddy College of Pharmacy, Mehdipatnam, Hyderabad, Telangana, India.

Harini K
Department of Pharmaceutics, G. Pulla Reddy College of Pharmacy, Mehdipatnam, Hyderabad, Telangana, India.


Article Tools


Email this article (Login required)
Email the author (Login required)

Refbacks

  • There are currently no refbacks.