FORMULATIONS AND TECHNOLOGIES IN GROWTH HORMONE DELIVERY


Gubran Khalil Mohammed, Rana M. Obaidat, Shereen Assaf, Mai Khanfar, Bashar Al-taani

Abstract


Growth hormone treatment has many indications including the treatment of growth hormone deficiency, Prader–Willi syndrome, chronic renal insufficiency, Turner syndrome, AIDS-related wasting, idiopathic short stature in children, and accumulation of fat which related in adults with lipodystrophy. Conventional therapy was achieved using intramuscular and subcutaneous injections. However, noncompliance was very high. To solve this; many studies have been attempted to prepare long-acting formulations and new to make derivatives of growth hormone and to use alternative routes of administration which term as noninvasive routes such as intranasal, pulmonary, transdermal and oral. New delivery systems were also used such as needle-free and auto-injector devices. In this review, different formulations, technologies, and routes of growth hormone delivery will be presented with the discussion of the principles of formulations and selected additives that were used to achieve improved growth hormone formulations.


Keywords


Growth Hormone, Growth Hormone Delivery, Long-acting formulations, Alternative Routes.

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References


“RCSB PDB - 1HWG: 1:2 COMPLEX OF HUMAN GROWTH HORMONE WITH ITS SOLUBLE BINDING PROTEIN Structure Summary Page.” [Online]. Available: http://www.rcsb.org/pdb/explore/explore.do?structureId=1HWG. [Accessed: 24-Jan-2017].

J. D. Veldhuis, “A tripeptidyl ensemble perspective of interactive control of growth hormone secretion.,” Horm. Res., vol. 60, no. Suppl 1, pp. 86–101, 2003.

P. Zizzari and M. T. Bluet-Pajot, “Ghrelin, from GH secretagogue to orexigenic peptide,” Corresp. en Metab. Horm. Diabetes Nutr., vol. 8, pp. 58–65, 2004.

S. Yi, B. Bernat, G. Pal, A. Kossiakoff, and W.-H. Li, “Functional promiscuity of squirrel monkey growth hormone receptor toward both primate and nonprimate growth hormones.,” Mol. Biol. Evol., vol. 19, no. 7, pp. 1083–1092, Jul. 2002.

J. Cázares-Delgadillo, a Ganem-Rondero, and Y. N. Kalia, “Human growth hormone: new delivery systems, alternative routes of administration, and their pharmacological relevance.,” Eur. J. Pharm. Biopharm., vol. 78, no. 2, pp. 278–88, 2011.

M. A. Preece, “Diagnosis and treatment of children with growth hormone deficiency.,” Clin. Endocrinol. Metab., vol. 11, no. 1, pp. 1–24, 1982.

G. McGauley, “The psychological consequences and quality of life in adults with growth hormone deficiency.,” Growth Horm. IGF Res., vol. 10 Suppl B, pp. S63–S68, 2000.

et al. Christiansen, J. Sandahl, “‘Absorption of human growth hormone injected subcutaneously and intramuscularly in growth deficient dwarfs.,’” p. 1540., 1981.

E. L. and Company, “Humatrope_ somatropin (rDNA origin) for injection,” 2009.

N. Vahl, N. Møller, T. Lauritzen, J. S. Christiansen, and J. O. Jørgensen, “Metabolic effects and pharmacokinetics of a growth hormone pulse in healthy adults: relation to age, sex, and body composition.,” J. Clin. Endocrinol. Metab., vol. 82, no. 11, pp. 3612–3618, 1997.

A. Keller et al., “Pharmacokinetics and pharmacodynamics of GH: Dependence on route and dosage of administration,” Eur. J. Endocrinol., vol. 156, pp. 647–653, 2007.

E. O. Reiter et al., “A multicenter study of the efficacy and safety of sustained release GH in the treatment of naive pediatric patients with GH deficiency.,” J. Clin. Endocrinol. Metab., vol. 86, no. 10, pp. 4700–6, 2001.

D. M. Cook et al., “The Pharmacokinetic and Pharmacodynamic Characteristics of a Long-Acting Growth Hormone (GH) Preparation (Nutropin Depot) in GH-Deficient Adults,” J. Clin. Endocrinol. Metab., vol. 87, no. 10, pp. 4508–4514, 2002.

H. H. Kwak et al., “Development of a sustained-release recombinant human growth hormone formulation.,” J. Control. Release, vol. 137, no. 2, pp. 160–5, 2009.

Y. Wei et al., “A novel sustained-release formulation of recombinant human growth hormone and its pharmacokinetic, pharmacodynamic and safety profiles,” Mol. Pharm., vol. 9, no. 7, pp. 2039–2048, 2012.

C. Govardhan et al., “Novel long-acting crystal formulation of human growth hormone.,” Pharm. Res., vol. 22, no. 9, pp. 1461–70, 2005.

S. J. Kim, S. K. Hahn, M. J. Kim, D. H. Kim, and Y. P. Lee, “Development of a novel sustained release formulation of recombinant human growth hormone using sodium hyaluronate microparticles,” J. Control. Release, vol. 104, no. 2, pp. 323–335, 2005.

M. Bidlingmaier et al., “Comparative pharmacokinetics and pharmacodynamics of a new sustained-release growth hormone (GH), LB03002, versus daily GH in adults with GH deficiency,” J. Clin. Endocrinol. Metab., vol. 91, no. 8, pp. 2926–2930, 2006.

F. Jordan, a. Naylor, C. a. Kelly, S. M. Howdle, a. Lewis, and L. Illum, “Sustained release hGH microsphere formulation produced by a novel supercritical fluid technology: In vivo studies,” J. Control. Release, vol. 141, no. 2, pp. 153–160, 2010.

K. J. Brodbeck, S. Pushpala, and a J. McHugh, “Sustained release of human growth hormone from PLGA solution depots.,” Pharmaceutical research, vol. 16, no. 12. pp. 1825–9, 1999.

A. R. Hoffman et al., “Efficacy of a long-acting growth hormone (GH) preparation in patients with adult GH deficiency,” J. Clin. Endocrinol. Metab., vol. 90, no. 12, pp. 6431–6440, 2005.

R. Webster et al., “PEGylated proteins: Evaluation of their safety in the absence of definitive metabolism studies,” Drug Metab. Dispos., vol. 35, no. 1, pp. 9–16, 2007.

R. Webster et al., “PEGylation of somatropin (recombinant human growth hormone): impact on its clearance in humans.,” Xenobiotica., vol. 38, no. 10, pp. 1340–51, 2008.

P. Touraine et al., “Lipoatrophy in GH deficient patients treated with a long-acting pegylated GH.,” Eur. J. Endocrinol., vol. 161, no. 4, pp. 533–40, 2009.

M. H. Rasmussen, L. Jensen, T. W. Anderson, T. Klitgaard, and J. Madsen, “Multiple doses of pegylated long-acting growth hormone are well tolerated in healthy male volunteers and possess a potential once-weekly treatment profile.,” Clin. Endocrinol. (Oxf)., vol. 73, no. 6, pp. 769–76, 2010.

J. de Schepper, M. H. Rasmussen, Z. Gucev, A. Eliakim, and T. Battelino, “Long-acting pegylated human GH in children with GH deficiency: a single-dose, dose-escalation trial investigating safety, tolerability, pharmacokinetics and pharmacodynamics.,” Eur. J. Endocrinol., vol. 165, no. 3, pp. 401–9, 2011.

K. Racz et al., “OR7-6: Safety and efficacy of ARX201: six month dose-ranging study of a novel long-acting pegylated growth hormone in young adults with growth hormone deficiency,” Growth Horm. IGF Res., vol. 24, p. S20, 2014.

G. N. Cox, M. S. Rosendahl, E. a Chlipala, D. J. Smith, S. J. Carlson, and D. H. Doherty, “A long-acting, mono-PEGylated human growth hormone analog is a potent stimulator of weight gain and bone growth in hypophysectomized rats.,” Endocrinology, vol. 148, no. 4, pp. 1590–7, 2007.

G. Pasut, A. Mero, F. Caboi, L. Sollai, F. M. Veronese, and S. Scaramuzza, “Article A New PEG ## -Alanine Active Derivative for Releasable Protein Conjugation A New PEG - -Alanine Active Derivative for Releasable Protein,” pp. 2427–2431, 2008.

C. Höybye, A. F. H. Pfeiffer, D. Ferone, D. Gilfoyle, M. Beckert, and J. S. Christiansen, “OR03-5 A phase 2, multicenter, multiple-dose, open-label, parallel-group, active controlled, safety, tolerability, pharmacokinetic and pharmacodynamic study of ACP-001 in adult patients with Growth Hormone Deficiency (AGHD),” Growth Horm. IGF Res., vol. 22, pp. S8–S9, 2012.

M. H. Rasmussen, M. W. B. Olsen, L. Alifrangis, S. Klim, and M. Suntum, “A Reversible Albumin-Binding Growth Hormone Derivative is Well Tolerated and Possesses a Potential Once-Weekly Treatment Profile.,” J. Clin. Endocrinol. Metab., vol. 99, no. 10, pp. E1819-29, 2014.

B. L. Osborn et al., “Albutropin : a growth hormone – albumin fusion with improved pharmacokinetics and pharmacodynamics in rats and monkeys,” Eur J Pharmacol, vol. 456, no. 1–3, pp. 149–158, 2002.

J. L. Cleland et al., “A novel long-acting human growth hormone fusion protein (VRS-317): enhanced in vivo potency and half-life.,” J. Pharm. Sci., vol. 101, no. 8, pp. 2744–2754, Aug. 2012.

M. I. Goth et al., “P03-37 Once-weekly, CTP-modified hGH (MOD-4023) is effective in growth hormone deficient adults: A phase II, dose and frequency finding study,” Growth Horm. IGF Res., vol. 22, pp. S84–S85, 2012.

E.-S. Kim et al., “Controlled release of human growth hormone fused with a human hybrid Fc fragment through a nanoporous polymer membrane.,” Nanoscale, vol. 5, no. 10, pp. 4262–9, 2013.

K. Manohar, W. R. Ravis, D. L. Golden, and A. K. Banga, “journal of pharmaceutics Controlled release of human growth hormone following subcutaneous administration in dogs,” Solutions, vol. 152, pp. 1993–1998, 1997.

G. Tae, J. a Kornfield, and J. a Hubbell, “Sustained release of human growth hormone from in situ forming hydrogels using self-assembly of fluoroalkyl-ended poly(ethylene glycol).,” Biomaterials, vol. 26, no. 25, pp. 5259–66, 2005.

H. S. Yoo, “Photo-cross-linkable and thermo-responsive hydrogels containing chitosan and Pluronic for sustained release of human growth hormone (hGH).,” J. Biomater. Sci. Polym. Ed., vol. 18, no. 11, pp. 1429–1441, 2007.

U. P. Shinde, M. K. Joo, H. J. Moon, and B. Jeong, “Sol-gel transition of PEG-PAF aqueous solution and its application for hGH sustained release,” J. Mater. Chem., vol. 22, no. 13, pp. 6072–6079, 2012.

M.-R. Park, C. Chun, S.-W. Ahn, M.-H. Ki, C.-S. Cho, and S.-C. Song, “Sustained delivery of human growth hormone using a polyelectrolyte complex-loaded thermosensitive polyphosphazene hydrogel,” J. Control. Release, vol. 147, no. 3, pp. 359–367, 2010.

J. García, M. J. Dorta, O. Munguía, M. Llabrés, and J. B. Fariña, “Biodegradable laminar implants for sustained release of recombinant human growth hormone.,” Biomaterials, vol. 23, no. 24, pp. 4759–64, 2002.

E. Fidotti, “A history of growth hormone injection devices.,” J. Pediatr. Endocrinol. Metab., vol. 14, no. 5, pp. 497–501, 2001.

H. Dumas, P. Panayiotopoulos, D. Parker, and V. Pongpairochana, “Understanding and meeting the needs of those using growth hormone injection devices.,” BMC Endocr. Disord., vol. 6, p. 5, 2006.

G. H. Verrips, R. a Hirasing, M. Fekkes, T. Vogels, S. P. Verloove-Vanhorick, and H. a Delemarre-Van De Waal, “Psychological responses to the needle-free Medi-Jector or the multidose Disetronic injection pen in human growth hormone therapy.,” Acta Paediatr., vol. 87, no. 2, pp. 154–158, 1998.

H. Agerso, J. Moller-Pedersen, S. Cappi, P. Thomann, B. Jesussek, and T. Senderovitz, “Pharmacokinetics and pharmacodynamics of a new formulation of recombinant human growth hormone administered by ZomaJet 2 Vision, a new needle-free device, compared to subcutaneous administration using a conventional syringe.,” J. Clin. Pharmacol., vol. 42, no. 11, pp. 1262–1268, Nov. 2002.

H. G. Dörr et al., “Are needle-free injections a useful alternative for growth hormone therapy in children? Safety and pharmacokinetics of growth hormone delivered by a new needle-free injection device compared to a fine gauge needle.,” J. Pediatr. Endocrinol. Metab., vol. 16, no. 3, pp. 383–92, 2003.

C. Brearley, A. Priestley, J. Leighton-Scott, and M. Christen, “Pharmacokinetics of recombinant human growth hormone administered by cool. clickTM 2, a new needle-free device, compared with subcutaneous administration using a conventional syringe and needle,” BMC Pharmacol. Toxicol., vol. 7, no. 1, p. 10, 2007.

L. Illum, “Nasal drug delivery—possibilities, problems and solutions,” J. Control. Release, vol. 87, no. 1–3, pp. 187–198, 2003.

L. Jorgensen and E. Bechgaard, “Intranasal permeation of thyrotropin-releasing hormone: in vitro study of permeation and enzymic degradation.,” Sect. Title Pharm., vol. 107, no. 3, pp. 231–237, 1994.

a S. Harris, I. M. Nilsson, Z. G. Wagner, and U. Alkner, “Intranasal administration of peptides: nasal deposition, biological response, and absorption of desmopressin.,” J. Pharm. Sci., vol. 75, no. 11, pp. 1085–8, 1986.

P. A. Baldwin, C. K. Klingbeil, C. J. Grimm, and J. P. Longenecker, “The effect of sodium tauro-24,25-dihydrofusidate on the nasal absorption of human growth hormone in three animal models.,” Pharm. Res., vol. 7, no. 5, pp. 547–552, May 1990.

L. Hedin, S. Petersson, and S. Rosberg, “of Human Growth Hormone ( hGH ) in Combination with a Membrane in Patients with GH Deficiency :,” no. October, pp. 962–967, 1993.

A. N. Fisher, N. F. Farraj, D. T. O’Hagan, I. Jabbal-Gill, L. Illum, and et al., “Effect of L-alpha-lysophosphatidylcholine on the nasal absorption of human growth hormone in three animal species,” Int. J. Pharm., vol. 74, pp. 147–156, 1991.

L. Illum, N. F. Farraj, S. S. Davis, B. R. Johansen, and D. T. O’Hagan, “Investigation of the nasal absorption of biosynthetic human growth hormone in sheep--use of a bioadhesive microsphere delivery system,” Int. J. Pharm., vol. 63, pp. 207–211, 1990.

H. Nielsen, “Epithelial Transport and Bioavai lability of lntranasall y Administered Human Growth Hormone Formulated with the Absorption Enhancers,” vol. 83, no. 12, pp. 3–8, 1994.

T. Laursen, B. Grandjean, J. O. Jørgensen, and J. S. Christiansen, “Bioavailability and bioactivity of three different doses of nasal growth hormone (GH) administered to GH-deficient patients: comparison with intravenous and subcutaneous administration.,” Eur. J. Endocrinol., vol. 135, no. 3, pp. 309–15, 1996.

V. M. Leitner, D. Guggi, and A. Bernkop-Schnürch, “Thiomers in noninvasive polypeptide delivery: in vitro and in vivo characterization of a polycarbophil-cysteine/glutathione gel formulation for human growth hormone.,” J. Pharm. Sci., vol. 93, no. 7, pp. 1682–91, 2004.

V. M. Leitner, D. Guggi, A. H. Krauland, and A. Bernkop-Schnürch, “Nasal delivery of human growth hormone: in vitro and in vivo evaluation of a thiomer/glutathione microparticulate delivery system.,” J. Control. Release, vol. 100, no. 1, pp. 87–95, 2004.

Y.-H. Cheng et al., “Intranasal delivery of recombinant human growth hormone (somatropin) in sheep using chitosan-based powder formulations.,” Eur. J. Pharm. Sci., vol. 26, no. 1, pp. 9–15, 2005.

D. Steyn, L. Plessis, and A. Kotzé, “Nasal Delivery of Recombinant Human Growth Hormone : In Vivo Evaluation with Pheroid TM Technology and N-Trimethyl Chitosan Chloride,” vol. 13, no. 2, pp. 263–273, 2010.

L. Illum, F. Jordan, and A. L. Lewis, “CriticalSorb: a novel efficient nasal delivery system for human growth hormone based on Solutol HS15.,” J. Control. Release, vol. 162, no. 1, pp. 194–200, 2012.

R. U. Agu, M. I. Ugwoke, M. Armand, R. Kinget, and N. Verbeke, “The lung as a route for systemic delivery of therapeutic proteins and peptides.,” Respir. Res., vol. 2, no. 4, pp. 198–209, 2001.

C. Lombry, D. a Edwards, V. Préat, and R. Vanbever, “Alveolar macrophages are a primary barrier to pulmonary absorption of macromolecules.,” Am. J. Physiol. Lung Cell. Mol. Physiol., vol. 286, pp. L1002–L1008, 2004.

H. Chrystyn, “Is total particle dose more important than particle distribution?,” Respir. Med., vol. 91 Suppl A, pp. 17–9, 1997.

H. G. Folkesson, L. Hedin, and B. R. Weström, “Lung to blood passage of human growth hormone after intratracheal instillation: stimulation of growth in hypophysectomized rats.,” J. Endocrinol., vol. 134, pp. 197–203, 1992.

P. Colthorpe, S. J. Farr, I. J. Smith, D. Wyatt, and G. Taylor, “The influence of regional deposition on the pharmacokinetics of pulmonary-delivered human growth hormone in rabbits.,” Pharm. Res., vol. 12, no. 3, pp. 356–359, Mar. 1995.

C. Bosquillon, V. Préat, and R. Vanbever, “Pulmonary delivery of growth hormone using dry powders and visualization of its local fate in rats,” J. Control. Release, vol. 96, no. 2, pp. 233–244, 2004.

M. Jalalipour, A. R. Najafabadi, K. Gilani, H. Esmaily, and H. Tajerzadeh, “Effect of dimethyl-beta-cyclodextrin concentrations on the pulmonary delivery of recombinant human growth hormone dry powder in rats.,” J. Pharm. Sci., vol. 97, no. 12, pp. 5176–5185, Dec. 2008.

Y. B. Schuetz, A. Naik, R. H. Guy, and Y. N. Kalia, “Emerging strategies for the transdermal delivery of peptide and protein drugs.,” Expert Opin. Drug Deliv., vol. 2, no. 3, pp. 533–548, 2005.

L. G. et al., “Transdermal delivery of human growth hormone through RF-microchannels,” Pharm. Res., vol. 22, no. 4, pp. 550–555, 2005.

Y. Ito, Y. Ohashi, K. Shiroyama, N. Sugioka, and K. Takada, “Self-dissolving micropiles for the percutaneous absorption of recombinant human growth hormone in rats.,” Biol. Pharmacetical Bull., vol. 31, no. 8, pp. 1631–3, 2008.

J. W. Lee, S. O. Choi, E. I. Felner, and M. R. Prausnitz, “Dissolving microneedle patch for transdermal delivery of human growth hormone,” Small, vol. 7, no. 4, pp. 531–539, 2011.

K. Fukushima et al., “Two-Layered Dissolving Microneedles for Percutaneous Delivery of Peptide/Protein Drugs in Rats,” Pharm. Res., vol. 28, no. 1, pp. 7–21, 2011.

M. H. XIAOLING LI, ORAL BIOAVAILABILITY Basic Principles, Advanced Concepts, and Applications. 2011.

A. Leone-bay et al., “4- [ 4- [( 2-Hydroxybenzoyl ) Amino ] Phenyl ] Butyric Acid as a Novel Oral Delivery Agent for Recombinant Human Growth Hormone,” Mater. Chem., vol. 2623, no. 96, pp. 2571–2578, 1996.

S. J. Wu and J. R. Robinson, “Transcellular and lipophilic complex-enhanced intestinal absorption of human growth hormone.,” Pharm. Res., vol. 16, no. 8, pp. 1266–1272, Aug. 1999.

H. Yoshiura et al., “Design and in vivo evaluation of solid-in-oil suspension for oral delivery of human growth hormone,” Biochem. Eng. J., vol. 41, no. 2, pp. 106–110, 2008.

N. Amet, W. Wang, and W. C. Shen, “Human growth hormone-transferrin fusion protein for oral delivery in hypophysectomized rats,” J. Control. Release, vol. 141, no. 2, pp. 177–182, 2010.

Y. Ni, J. Yu, J.-P. Xu, and X.-L. Meng, “Enhanced delivery of human growth hormone across cell membrane by Tat-PTD.,” Endocrine, vol. 46, no. 1, pp. 138–47, 2014.

E. Technologies, “Oral Human Growth Hormone,” 2004.

J. Parmentier et al., “Improved Oral Bioavailability of Human Growth Hormone by a Combination of Liposomes Containing Bio-Enhancers and Tetraether Lipids and Omeprazole,” J. Pharm. Sci., vol. 103, no. 12, pp. 3985–3993, 2014.




About this article

Title

FORMULATIONS AND TECHNOLOGIES IN GROWTH HORMONE DELIVERY

Keywords

Growth Hormone, Growth Hormone Delivery, Long-acting formulations, Alternative Routes.

DOI

10.22159/ijpps.2017.v9i7.18079

Date

01-07-2017

Additional Links

Manuscript Submission

Journal

International Journal of Pharmacy and Pharmaceutical Sciences
Vol 9, Issue 7, 2017 Page: 1-12

Online ISSN

0975-1491

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Authors & Affiliations

Gubran Khalil Mohammed
Pharmaceutical Technology Department, Faculity of Pharmacy, Jordan University of Science and Technology, Irbid, jordan
Jordan

Rana M. Obaidat
Pharmaceutical Technology Department, Faculity of Pharmacy, Jordan University of Science and Technology, Irbid, jordan
Jordan

Shereen Assaf
Pharmaceutical Technology Department, Faculity of Pharmacy, Jordan University of Science and Technology, Irbid, jordan
Jordan

Mai Khanfar
Pharmaceutical Technology Department, Faculity of Pharmacy, Jordan University of Science and Technology, Irbid, jordan

Bashar Al-taani
Pharmaceutical Technology Department, Faculity of Pharmacy, Jordan University of Science and Technology, Irbid, jordan


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