title: Intranasal delivery of recombinant human growth hormone (somatropin) in sheep using chitosan-based powder formulations.
abstract: The effectiveness of chitosan in promoting the intranasal bioavailability of recombinant human growth hormone (hGH) has been evaluated. hGH was formulated with chitosan to produce a powder blend (Formulation A) and granules (Formulation B) for intranasal administration. The in vivo pharmacokinetic performance of the formulations was evaluated in a group of six sheep in a randomised crossover study. A subcutaneous injection of hGH solution was administered as a control. The intranasal and subcutaneous doses of hGH were 0.3 and 0.03 mg/kg, respectively. The intranasal formulations appeared to be well tolerated. Mean bioavailabilities of hGH from Formulations A and B were 14 and 15%, respectively relative to subcutaneous injection. It is concluded that chitosan-based intranasal powder formulations may provide a practical means for non-injectable delivery of hGH and, potentially, other therapeutic protein molecules.
authors.affiliation: Archimedes Development Ltd., Albert Einstein Centre, Nottingham Science and Technology Park, University Boulevard, Nottingham, NG7 2TN, UK.
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Cheng
authors.forename: A Margaret
authors.initials: AM
authors.lastname: Dyer
authors.forename: Inderjit
authors.initials: I
authors.lastname: Jabbal-Gill
authors.forename: Michael
authors.initials: M
authors.lastname: Hinchcliffe
authors.forename: Richard
authors.initials: R
authors.lastname: Nankervis
authors.forename: Alan
authors.initials: A
authors.lastname: Smith
authors.forename: Peter
authors.initials: P
authors.lastname: Watts
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry; D018592:Cross-Over Studies; D016503:Drug Delivery Systems / Q000379:methods*; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D011208:Powders; D011897:Random Allocation; D011994:Recombinant Proteins / Q000008:administration & dosage; D012756:Sheep; D013997:Time Factors
chemical_list: D011208:Powders; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D048271:Chitosan