Intranasal delivery of recombinant human growth hormone (somatropin) in sheep using chitosan-based powder formulations

Dyer, A. M.; Jabbal‐Gill, Inderjit; Hinchcliffe, Michael; Nankervis, R.; Smith, Alan M.; Watts, Peter

doi:10.1016/j.ejps.2005.03.014

Cited by 39 publications

(18 citation statements)

References 24 publications

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“…57 Formulations of chitosan and rhGH mixture, in powder and granule forms, achieved bioavailability of 14% and 15%, respectively, in sheep. 58 Moreover, its effect on the integrity of nasal membrane proved to be minimal in rats. 59 The mechanism of effect of the chitosan was suggested to be a combination of bioadhesion and a transient widening of the tight junctions in the membrane.…”

Section: Intranasal Deliverymentioning

confidence: 99%

Developments in human growth hormone preparations: sustained-release, prolonged half-life, novel injection devices, and alternative delivery routes

Cai¹,

Xu²,

Yuan³

et al. 2014

IJN

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Since the availability of recombinant human growth hormone (rhGH) enabled the application of human growth hormone both in clinical and research use in the 1980s, millions of patients were prescribed a daily injection of rhGH, but noncompliance rates were high. To address the problem of noncompliance, numerous studies have been carried out, involving: sustained-release preparations, prolonged half-life derivatives, new injectors that cause less pain, and other noninvasive delivery methods such as intranasal, pulmonary and transdermal deliveries. Some accomplishments have been made and launched already, such as the Nutropin Depot ® microsphere and injectors (Zomajet ® , Serojet ® , and NordiFlex ® ). Here, we provide a review of the different technologies and illustrate the key points of these studies to achieve an improved rhGH product.

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Section: Intranasal Deliverymentioning

confidence: 99%

Developments in human growth hormone preparations: sustained-release, prolonged half-life, novel injection devices, and alternative delivery routes

Cai¹,

Xu²,

Yuan³

et al. 2014

IJN

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“…Several experimental delivery systems for the improved nasal delivery of rhGH have been described. These include dry polymer particles such as starch microspheres [10], chitosan [11] and a thiomer/glutathione microparticulate delivery system [12].…”

Section: ________________________________________mentioning

confidence: 99%

Nasal Delivery of Recombinant Human Growth Hormone: In Vivo Evaluation with Pheroid™ Technology and N-Trimethyl Chitosan Chloride

Steyn¹,

Plessis

Kotzé³

2010

J Pharm Pharm Sci

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-Purpose. It was the aim of this study to investigate the possible enhancement of the absorption of recombinant human growth hormone (rhGH) in the nasal cavity, in the presence of a polymeric absorption enhancer, N-trimethyl chitosan chloride (TMC) and a patented fatty acid-based delivery system, Pheroid. Methods. Two types of Pheroid formulations, Pheroid vesicles and Pheroid microsponges were characterized and evaluated with regard to particle size and morphology. In vivo bioavailability studies in rats were performed and the nasal bioavailability of Pheroid vesicles and Pheroid microsponges were compared relative to subcutaneous administration. The results were also compared with different N-trimethyl chitosan chloride (TMC) formulations, TMC H-L and TMC H-H, well studied absorption enhancers. Results. Pheroid vesicles and Pheroid microsponges showed a size distribution of approximately 2-3 µm and 3-4 µm for Pheroid vesicles and Pheroid microsponges respectively. Using specific RIA, the relative bioavailability of rhGH after comparison with subcutaneous injection was determined to be 38.9, 128.5, 39.9, 136.3, and 8.3 % for Pheroid microsponges, Pheroid vesicles, TMC H-H, TMC H-L and control group (intranasal rhGH alone), respectively. All the enhancers showed significant absorption enhancement (P < 0.05) with the highest effect observed with TMC H-L. Conclusion. All the enhancers may have promising potential as safe and effective nasal absorption enhancers of rhGH.The Pheroid delivery system is a novel patented system consisting of a unique submicron emulsion type formulation. The system, which consist mainly of essential fatty acids can entrap and transport pharmacological active compounds. In this study it is shown that two types of Pheroid formulations, Pheroid vesicles and Pheroid microsponges, have the ability to entrap recombinant human growth hormone and improve the nasal absorption and thus bioavailability of rhGH. Intranasal administration of rhGH entrapped in Pheroid technology is an attractive alternative to subcutaneous of intravenous administration. _______________________________________________________________________________________

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“…9 The application of absorption enhancers were often studied in mucoadhesive like formulations in the form of liquids, gelling systems, nanoparticles and microspheres by few authors to better approach the transport of peptides and proteins across the nasal mucosa. [10][11][12][13][14][15][16] Of special interest has been the use of chitosan as an absorption enhancer and a bioadhesive materials acting by opening the tight junctions of nasal mucosa to overcome the high degree effect of the mucociliary clearance by increasing the residence time of the formulation in the nasal cavity. 17 Chitosan, a natural linear polycationic, biocompatible, biodegradable and mucoadhesive polymer derives from alkaline deacetylation of chitin of several Mw (10kDa-2000kDa) with varying degrees of deacetylation (40-98%).…”

Section: Introductionmentioning

confidence: 99%

Mucoadhesive Microspheres of Chitosan and Polyvinyl Alcohol as A Carrier for Intranasal Delivery of Insulin: In Vitro and In Vivo Studies

Darbandi¹

2017

MOJBB

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The aim of this study was to investigate the capabilities of chitosan microspheres as drug carrier system in co-formulation with polyvinyl alcohol (PVA), to improve the systemic absorption of intranasal insulin delivery.Insulin loaded microspheres was developed from varying ratio of chitosan solutions along with polyvinyl alcohol (PVA) as additive polymer using spray drying method. Different formulations were developed and morphological studies of the optimized formulas showed that the size range of spherical shaped particulate matters existed from 200 nm to 2 μm. It was clearly observed that physicochemical properties of the microspheres were extensively affected by changing the concentration ratio of the two polymeric materials. In vitro studies of insulin release pattern was performed in various time intervals up to 24 h. It was evident that microspheres made up of chitosan showed initial burst release but slower release as the experiment continued. Microspheres made up of combination of the aforementioned two polymers had instant, sharp and burst drug release. Surprisingly there was no absorption after intranasal delivery of chitosan-PVA microspheres in groups of rats comparing to formulated chitosan microspheres having profound absorption due to their smaller particle size, slower drug release rate and better mucoadhesive properties. Therefore, significant reduction in the plasma blood glucose level for chitosan based optimized formulation was seen right after 4.5 hours compared with control group. The aim of the present study was to fabricate an appropriate application of polymeric microspheres for intranasal delivery of insulin using a novel optimized formulation based on industrial level spray drying technique and to realize the possible barriers in scale up process of its large scale production, considering the effectiveness of polyvinyl alcohol (PVA) and chitosan to increase mucoadhesivness, gelling ability and ultimately effective release behavior pattern of insulin. According to this study, the combination of the polymers used and the mean particle size of formulated microspheres were found to be key factors in insulin drug release resulting for further enhancement of insulin absorption via intranasal route of delivery. Furthermore, avoidance of hepatic first pass metabolism makes it a preferred route for the delivery of small drug molecules but not basically the macromolecules as the permeability and degradability are rate-limiting steps in their systemic absorptions. KeywordsFeasibility of intranasal route for delivery of peptides and proteins has already been evaluated as mentioned before, due to the perceived less demanding barriers to peptides and proteins transport across the nasal epithelium as compared to the oral mucosa and nasal cavity comprising lower enzymatic content, higher leakiness of the membrane and high vascularity and no hepatic first pass metabolism But still there are few nasal peptide based products which have appeared on the market e.g. calcitonin (Miacalcin These prod...

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Intranasal delivery of recombinant human growth hormone (somatropin) in sheep using chitosan-based powder formulations

Cited by 39 publications

References 24 publications

Developments in human growth hormone preparations: sustained-release, prolonged half-life, novel injection devices, and alternative delivery routes

Developments in human growth hormone preparations: sustained-release, prolonged half-life, novel injection devices, and alternative delivery routes

Nasal Delivery of Recombinant Human Growth Hormone: In Vivo Evaluation with Pheroid™ Technology and N-Trimethyl Chitosan Chloride

Mucoadhesive Microspheres of Chitosan and Polyvinyl Alcohol as A Carrier for Intranasal Delivery of Insulin: In Vitro and In Vivo Studies

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