Journal Article Development of a Transnasal Delivery System for Recombinant Human Growth Hormone (rhGH): Effects of the Concentration and MolecularWeight of Poly-L-arginine on the Nasal Absorption of rhGH in Rats

川島, 亮  ,  内田, 昌希  ,  八巻, 努  ,  大竹, 一男  ,  畑中, 朋美  ,  内田, 博之  ,  上田, 秀雄  ,  小林, 順  ,  森本, 雍憲  ,  夏目, 秀視

39 ( 3 )  , pp.329 - 335 , 2016-03 , 日本薬学会
ISSN:0918-61581347-5215
NCID:AA10885497
Description
A novel system for delivering recombinant human growth hormone (rhGH) that is noninvasive and has a simple method of administration is strongly desired to improve the compliance of children. The aim of this study was to investigate the potential for the intranasal (i.n.) co-administration of rhGH with poly-L-arginine (PLA) as a novel delivery system by evaluating the effects of the concentration and molecular weight of PLA on the nasal absorption of rhGH. The influence of the formation of insoluble aggregates and a soluble complex in the dosage formulation on nasal rhGH absorption was also evaluated by size-exclusion chromatography and ultrafiltration. PLA enhanced the nasal absorption of rhGH at each concentration and molecular weight examined. Nasal rhGH absorption increased dramatically when the PLA concentration was 1.0 % (w/v) due to the improved solubility of rhGH in the formulation. A delay in rhGH absorption was observed when the molecular weight of PLA was increased. This appeared to be because the increase in molecular weight caused the formation of a soluble complex. It seems that the PLA concentration affects the absorptionenhancing effect on rhGH, while the molecular weight of PLA affects the time when the maximum plasma rhGH concentration was reached (Tmax) of rhGH after i.n. administration, mainly because of the interactions among rhGH, PLA, and additives. Therefore, the transnasal rhGH delivery system using PLA is considered to be a promising alternative to subcutaneous (s.c.) injection if these interactions are sufficiently controlled.
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http://libir.josai.ac.jp/il/user_contents/02/G0000284repository/pdf/JOS-bpb.b15-00657.pdf

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