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Formulations for delivery of therapeutic proteins

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Abstract

Advances in biotechnology have now created a capacity to produce therapeutically active proteins on a commercial scale, opening the potential for their application in an array of disease conditions. The process of translation of the variety of different therapeutic proteins into the medicines used in clinics is now occurring. To assist in this translation, new formulations to deliver proteins could play an important role. These new formulations need to more adequately address the pharmacological and therapeutic requirement for each particular protein/peptide and, in that way, either improve present therapies or extend with new entries the current list of protein based medicines used in clinic.

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Notes

  1. http://www.fortical.com/docs/Professional_pi.pdf. Cited 29 July 2008.

  2. http://www.generex.com/index.php. Cited 16 July 2008.

  3. http://www.accesspharma.com/cobalamintargeted1.shtml. Accessed 29 July 2008.

References

  • Ahsan F, Arnold JJ, Yang T, Meezan E, Schwiebert EM, Pillion DJ (2003) Effects of the permeability enhancers, tetradecylmaltoside and dimethyl-ß-cyclodextrin, on insulin movement across human bronchial epithelial cells (16HBE14o-). Eur J Pharm Sci 20:27–34

    Article  PubMed  CAS  Google Scholar 

  • Alamdar H, Arnold JJ, Khan MA, Ahsan F (2004) Absorption enhancers in pulmonary protein delivery. J Control Release 94:15–24

    Article  Google Scholar 

  • Amidi M, Jiskoot W et al (2006) Preparation and characterization of protein-loaded N-trimethyl chitosan nanoparticles as nasal delivery system. J Control Release 111:107–116

    Article  PubMed  CAS  Google Scholar 

  • Ayala M, Horjales E, Pickard MA, Vazquez-Duhalt R (2002) Cross-linked crystals of chloroperoxidase. Biochem Biophys Res Commun 295:828–831

    Article  PubMed  CAS  Google Scholar 

  • Basu SK, Govardam CP, Jung CW, Margolin AL (2004) Protein crystals for the delivery of biopharmaceuticals. Expert Opin Biol Ther 4:301–317

    Article  PubMed  CAS  Google Scholar 

  • Bernkop-Schnurch A (2005) Thiomers: a new generation of mucoadhesive polymers. Adv Drug Deliv Rev 57:569–1582

    Google Scholar 

  • Betre H, Liu W, Zalutsky MR, Chilkoti A, Kraus VB, Setton LA (2006) A thermally responsive biopolymer for intra-articular drug delivery. J Control Release 115:175–182

    Article  PubMed  CAS  Google Scholar 

  • Boado RJ, Zhang Y, Wang Y, Pardridge WM (2008) GDNF fusion protein for targeted-drug delivery across the human blood–brain barrier. Biotechnol Bioeng 100:387–396

    Article  PubMed  CAS  Google Scholar 

  • Bromerg L, Rashba-Step J, Scott T (2005) Insulin particles formation in supersaturated aqueous solution of poly(ethylene glycol). Biophys J 89:3424–3433

    Article  Google Scholar 

  • Brooks H, Lebleu B, Vives E (2005) Tat peptide-mediated cellular delivery: back to basics. Adv Drug Deliv Rev 57:559–577

    Article  PubMed  CAS  Google Scholar 

  • Brown LR (2005) Commercial challenges of protein drug delivery. Expert Opin Drug Deliv 2:29–42

    Article  PubMed  Google Scholar 

  • Caliceti P, Veronese FM (2003) Pharmacokinetic and biodistribution properties of poly(ethylene glycol)-protein conjugates. Adv Drug Deliv Rev 55:1261–1277

    Article  PubMed  CAS  Google Scholar 

  • Charlton S, Whetstone J, Fayinka S, Read K, Illum L, Davis SS (2008) Evaluation of direct transport pathways of glycine receptor antagonists and an angiotensin antagonist from the nasal cavity to the central nervous system in the rat model. Pharm Res 25:1531–1543

    Article  PubMed  CAS  Google Scholar 

  • Chen SC, Eiting K, Cui K, Leonard AK, Morris D, Li CY, Farber K, Sileno AP, Houston ME Jr, Johnson PH, Quay SC, Costantino HR (2006) Therapeutic utility of a novel tight junction modulating peptide for enhancing intranasal drug delivery. J Pharm Sci 95:1364–1371

    Article  PubMed  CAS  Google Scholar 

  • Chen F-M, Zhao Y-M, Zhang R, Jin T, Sun H-H, Wu Z-F, Jin Y (2007a) Periodontal regeneration using novel glycidyl methacrylated dextran (Dex-GMA)/gelatin scaffolds containing microspheres loaded with bone morphogenetic proteins. J Control Release 121:81–90

    Article  PubMed  CAS  Google Scholar 

  • Chen RR, Silva EA, Yuen WW, Brock AA, Fischbach C, Lin AS, Guldberg RE, Mooney DJ (2007b) Integrated approach to designing growth factor delivery systems. FASEB J 21:3896–3903

    Article  PubMed  CAS  Google Scholar 

  • Chitkara D, Shikanov A, Kumar N, Domb AJ (2006) Biodegradable injectable in situ depot-forming drug delivery systems. Macromol Biosci 6:977–990

    Article  PubMed  CAS  Google Scholar 

  • Dalkara D, Zuber G, Behr JP (2004) Intracytoplasmic delivery of anionic proteins. Mol Ther 9:964–969

    Article  PubMed  CAS  Google Scholar 

  • Davies OR, Head L, Armitage D, Pearson EA, Davies MC, Marlow M, Stolnik S (2008a) Surface modification of microspheres with steric stabilising and cationic polymers for gene delivery. Langmuir 24:7138–7146

    Article  PubMed  CAS  Google Scholar 

  • Davies OR, Marlow M, Stolnik S (2008b) Macroporous surface modified microparticles. Soft Matter. doi:10.1039/b805421e

    PubMed  Google Scholar 

  • de Boer AG, Gaillard PJ (2007) Strategies to improve drug delivery across the blood–brain barrier. Clin Pharmacokinet 46:553–576

    Article  PubMed  Google Scholar 

  • El-Sayed MEH, Hoffman AS, Stayton PS (2005) Smart polymeric carriers for enhanced intracellular delivery of therapeutic macromolecules. Expert Opin Biol Ther 5:23–32

    Article  PubMed  CAS  Google Scholar 

  • Gao X, Wu B, Zhang Q, Chen J, Zhu J, Zhang W, Rong Z, Chen H, Jiang X (2007) Brain delivery of vasoactive intestinal peptide enhanced with the nanoparticles conjugated with wheat germ agglutinin following intranasal administration. J Control Release 121:156–167

    Article  PubMed  CAS  Google Scholar 

  • Govardham C, Khalaf N, Jung N, Jung CW, Simeone B, Higbie A, Qu S, Chemmalil L, Pechenov S, Basu SK, Margolin AL (2005) Novel long-acting crystal formulation of human growth hormone. Pharm Res 22:1461–1470

    Article  Google Scholar 

  • Groneberg DA, Fischer A, Fan Chung K, Hannelore D (2004) Molecular mechanisms of pulmonary peptidomimetic drug and peptide transport. Am J Respir Cell Mol Biol 30:251–260

    Article  PubMed  CAS  Google Scholar 

  • Haltner E, Easson JH, Lehr CM (1997) Lectins and bacterial invasion factors for controlling endo- and trancytosis of bioadhesive drug delivery systems. Eur J Pharm Biopharm 44:3–13

    Article  CAS  Google Scholar 

  • Illum L (2004) Is nose-to-brain transport of drugs in man a reality? J Pharm Pharmacol 56:3–17

    Article  PubMed  CAS  Google Scholar 

  • Ito T, Fraserb IP, Yeoa Y, Highleya CB, Bellasa E, Kohane DS (2007) Anti-inflammatory function of an in situ cross-linkable conjugate hydrogel of hyaluronic acid and dexamethasone. Biomaterials 28:1778–1786

    Article  PubMed  CAS  Google Scholar 

  • Jaklenec A, Wan E, Murray ME, Mathiowitz E (2008) Novel scaffolds fabricated from protein-loaded microspheres for tissue engineering. Biomaterials 29:185–192

    Article  PubMed  CAS  Google Scholar 

  • Jen A, Merkle HP (2001) Diamonds in the rough: protein crystals from a formulation perspective. Pharm Res 18:1483–1488

    Article  PubMed  CAS  Google Scholar 

  • Jepson MA, Clark MA, Hirst BH (2004) M cell targeting by lectins: a strategy for mucosal vaccination and drug delivery. Adv Drug Deliv Rev 56:511–525

    Article  PubMed  CAS  Google Scholar 

  • Katre NV (2004) Liposome-based depot injection technologies how versatile are they? Am J Drug Deliv 4:213–227

    Article  Google Scholar 

  • Kim MR, Park TG (2002) Temperature-responsive and degradable hyaluronic acid/Pluronic composite hydrogels for controlled release of human growth hormone. J Control Release 80:69–77

    Article  PubMed  CAS  Google Scholar 

  • Kondoh M, Yagi K (2007) Tight junction modulators: promising candidates for drug delivery. Med Chem 14:2482–2488

    CAS  Google Scholar 

  • Kondoh M, Takahashi A, Fujii M, Yagi K, Watanabe Y (2006) A novel strategy for a drug delivery system using a claudin modulator. Biol Pharm Bull 29:1783–1789

    Article  PubMed  CAS  Google Scholar 

  • Kranz H, Bodmeier R (2007) A novel in situ forming drug delivery system for controlled parenteral drug delivery. Int J Pharm 332:107–114

    Article  PubMed  CAS  Google Scholar 

  • Krauland AH, Schnurch AB et al (2006) Thiolated chitosan microparticles: a vehicle for nasal peptide drug delivery. Int J Pharm 307:270–277

    Article  PubMed  CAS  Google Scholar 

  • Kwon J-H, Lee B-H, Lee J-J, Kim C-W (2004) Insulin microcrystal suspension as a long-acting formulation for pulmonary delivery. Eur J Pharm Sci 22:107–116

    Article  PubMed  CAS  Google Scholar 

  • Lee JW, Park JH, Robinson JR (2000) Bioadhesive-based dosage forms: the next generation. J Pharm Sci 89:850–866

    Article  PubMed  CAS  Google Scholar 

  • Lee AL, Wang Y, Ye W-H, Yoon HS, Chan SY, Yang Y-Y (2008) Efficient intracellular delivery of functional proteins using cationic polymer core/shell nanoparticles. Biomaterials 29:1224–1232

    Article  PubMed  CAS  Google Scholar 

  • Leitner VM, Schnurch AB et al (2004) Nasal delivery of human growth hormone: in vitro and in vivo evaluation of thiomer/glutathione microparticulate delivery system. J Control Release 100:87–95

    Article  PubMed  CAS  Google Scholar 

  • Li H, Qian ZM (2002) Transferrin/transferrin receptor-mediated drug delivery. Med Res Rev 22:225–250

    Article  PubMed  CAS  Google Scholar 

  • Lin CC, Metters A (2006) Hydrogels in controlled release formulations: network design and mathematical modeling. Adv Drug Deliv Rev 58:1379–1408

    Article  PubMed  CAS  Google Scholar 

  • Lutolf MP, Lauer-Fields JL, Schmoekel HG, Metters AT, Weber FE, Fields GB, Hubbell JA (2003) Synthetic matrix metalloproteinase-sensitive hydrogels for the conduction of tissue regeneration: engineering cell-invasion characteristics. Proc Natl Acad Sci USA 100:5413–5418

    Article  PubMed  CAS  Google Scholar 

  • MacKay JA, Szoka FC Jr (2003) HIV TAT protein transduction domain mediated cell binding and intracellular delivery of nanoparticles. J Dispers Sci Technol 24:465–473

    Article  CAS  Google Scholar 

  • Mao S, Germershaus O, Fischer D, Linn T, Schnepf R, Kissel T (2005) Uptake and transport of PEG-graft-trimethyl-chitosan copolymer–insulin nanocomplexes by epithelial cells. Pharm Res 22:2058–2068

    Article  PubMed  CAS  Google Scholar 

  • Martins S, Sarmento B, Ferreira D et al (2007) Lipid-based colloidal carriers for peptide and protein delivery—liposomes versus lipid nanoparticles. Int J Nanomed 2:595–607

    CAS  Google Scholar 

  • Miyamoto M, Natsume H, Satoh I, Ohtake K, Yamaguchi M, Kobayashi D, Sugibayashi K, Morimoto Y (2001) Effect of poly-arginine on the nasal absorption of FITC-dextran of different molecular weights and recombinant human granulocyte colony-stimulating factor (rhG-CSF) in rats. Int J Pharm 226:127–138

    Article  PubMed  CAS  Google Scholar 

  • Morçöl T, Nagappan P, Nerenbaum L, Mitchell A, Bell SJD (2004) Calcium phosphate-PEG-insulin-casein (CAPIC) particles as oral delivery systems for insulin. Int J Pharm 277:91–97

    Article  PubMed  Google Scholar 

  • Morishita M, Peppas NA (2006) Is the oral route possible for peptide and protein drug delivery? Drug Discov Today 11:905–910

    Article  PubMed  CAS  Google Scholar 

  • Nam YS, Park JY, Han S-H, Chang I-S (2002) Intracellular drug delivery using poly(d, l-lactide-co-glycolide) nanoparticles derivatized with a peptide from a transcriptional activator protein of HIV-1. Biotechnol Lett 24:2093–2098

    Article  CAS  Google Scholar 

  • Okubo K, Minomi K, Pearson EA, Roberts C, Davies MC, Illum L, Stolnik S (2008) Mucosal transport studies on the excised tissue model. In: Proceedings of 35th annual meeting and exposition of the controlled release society, New York

  • Palframan R, Vugler A, Moore A, Baker M, Lightwood D, Nesbitt A, Foulkes R, Gozzard N (2007) Certolizumab pegol adalimumab accumulation in the inflammed paws of mice with collagen-induced arthritis compared to noninflammed tissue in vivo biofluorescence imaging of Alexa 680-labeled antibodies. Clin Immunol 123:S170

    Article  Google Scholar 

  • Pardridge WM (2007) Blood–brain barrier delivery of protein and non-viral gene therapeutics with molecular Trojan horses. J Control Release 122:345–348

    Article  PubMed  CAS  Google Scholar 

  • Peppas NA, Kim B (2006) Stimuli-sensitive protein delivery systems. J Drug Deliv Sci Technol 16:11–18

    CAS  Google Scholar 

  • Pharma Circle, Online database: http://www.pharmacircle.com. Cited July 29, 2008

  • Rubas W, Cromwell ME, Shahrokh Z (1996) Flux measurements across Caco-2 monolayers may predict transport in human large intestinal tissue. J Pharm Sci 85:165–169

    Article  PubMed  CAS  Google Scholar 

  • Spencer BJ, Verma IM (2007) Targeted delivery of proteins across the blood–brain barrier. Proc Natl Acad Sci USA 18:7594–7599

    Article  Google Scholar 

  • Stolnik S, Illum L, Davis SS (1995) Long circulating microparticulate drug carriers. Adv Drug Deliv Rev 16:195–214

    Article  CAS  Google Scholar 

  • Suciati T, Howard D, Barry J, Everitt NM, Shakesheff KM, Rose FRAJ (2006) Zonal release of proteins within tissue engineering scaffolds. J Mat Sci: Mat Med 17:1049–1056

    Article  CAS  Google Scholar 

  • Szebeni J (2005) Complement activation-related pseudoallergy: a new class of drug-induced acute immune toxicity. Toxicology 216:106–121

    Article  PubMed  CAS  Google Scholar 

  • Takeuchi H, Yamamoto H, Kawashima Y (2001) Mucoadhesive nanoparticulate systems for peptide drug delivery. Adv Drug Deliv Rev 47:39–54

    Article  PubMed  CAS  Google Scholar 

  • Tessmar JK, Goepferich AM (2007) Matrices and scaffolds for protein delivery in tissue engineering. Adv Drug Deliv Rev 59:274–291

    Article  PubMed  CAS  Google Scholar 

  • Trif M, Roseanu A, Brock JH, Brewer JM (2007) Designing lipid nanostructures for local delivery of biologically active macromolecules. J Liposome Res 17:237–248

    Article  PubMed  CAS  Google Scholar 

  • Tuesca A, Nakamura K, Morishita M, Joseph J, Peppas N, Lowman A (2007) Complexation hydrogels for oral insulin delivery: effects of polymer dosing on in vivo efficacy. J Pharm Sci 97:2607–2618

    Article  Google Scholar 

  • Tuma PL, Hubbard AL (2003) Transcytosis: crossing cellular barriers. Physiol Rev 83:871–932

    PubMed  CAS  Google Scholar 

  • Ungaro F, Biondi M, d’Angelo I, Indolfi L, Quaglia F, Netti PA, La Rotonda MI (2006) Microsphere-integrated collagen scaffolds for tissue engineering: effect of microsphere formulation and scaffold properties on protein release kinetics. J Control Release 113:128–136

    Article  PubMed  CAS  Google Scholar 

  • Van Tomme SR, Hennink WE (2007) Biodegradable dextran hydrogels for protein delivery applications. Expert Rev Med Devices 4:147–164

    Article  PubMed  Google Scholar 

  • Vila A, Gill H, McCallion O, Alonso MJ (2004) Transport of PLA-PEG particles across the nasal mucosa: effect of particle size and PEG coating density. J Control Release 98:231–244

    Article  PubMed  CAS  Google Scholar 

  • Wadia JS, Dowdy SF (2005) Transmembrane delivery of protein and peptide drugs by TAT-mediated transduction in the treatment of cancer. Adv Drug Deliv Rev 57:579–596

    Article  PubMed  CAS  Google Scholar 

  • Wagstaff KM, Jans DA (2006) Protein transduction: cell penetrating peptides and their therapeutic applications. Curr Med Chem 13:1371–1387

    Article  PubMed  CAS  Google Scholar 

  • Wei G, Jin Q, Giannobile WV, Ma PX (2007) The enhancement of osteogenesis by nano-fibrous scaffolds incorporating rhBMP-7 nanospheres. Biomaterials 28:2087–2096

    Article  PubMed  CAS  Google Scholar 

  • Whitaker MJ, Hao J, Davies OR, Serhatkulub G, Stolnik-Trenkic S, Howdle SM, Shakesheff KM (2005) The production of protein-loaded microparticles by supercritical fluid enhanced mixing and spraying. J Control Release 101:85–92

    Article  PubMed  CAS  Google Scholar 

  • Winter JA, Davies OR, Brown AP, Garnett MC, Stolnik S, Pritchard DI (2005) The assessment of hookworm calreticulin as a potential vaccine for necatoriasis. Parasite Immunol 27:139–146

    Article  PubMed  CAS  Google Scholar 

  • Woodley J (2001) Bioadhesion: new possibilities for drug administration? Clin Pharmacokinet 40:77–84

    Article  PubMed  CAS  Google Scholar 

  • Yakovlevski K (2004) Spherical protein particles and methods for making and using them, US Patent 2004/0219224A1

  • Zhang N, Chittasupho C, Duangrat C, Siahaan T, Berkland C (2008) PLGA nanoparticle-peptide conjugate effectively targets intercellular cell-adhesion molecule-1. Bioconjug Chem 19:145–152

    Article  PubMed  CAS  Google Scholar 

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  1. Drug Delivery and Tissue Engineering Division, School of Pharmacy, University of Nottingham, University Park, NG7 2RD, UK

    Snjezana Stolnik & Kevin Shakesheff

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  1. Snjezana Stolnik
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  2. Kevin Shakesheff
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Correspondence to Snjezana Stolnik.

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Stolnik, S., Shakesheff, K. Formulations for delivery of therapeutic proteins. Biotechnol Lett 31, 1–11 (2009). https://doi.org/10.1007/s10529-008-9834-y

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