Kawashima Ryo, Uchida Masaki, Yamaki Tsutomu, Ohtake Kazuo, Hatanaka Tomomi, Uchida Hiroyuki, Ueda Hideo, Kobayashi Jun, Morimoto Yasunori, Natsume Hideshi
Faculty of Pharmaceutical Sciences, Josai University.
Biol Pharm Bull. 2016;39(3):329-35. doi: 10.1248/bpb.b15-00657. Epub 2015 Dec 25.
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 absorption-enhancing 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.
人们强烈希望有一种新型的重组人生长激素（rhGH）递送系统，该系统无创且给药方法简单，以提高儿童的依从性。本研究的目的是通过评估聚-L-精氨酸（PLA）的浓度和分子量对rhGH鼻腔吸收的影响，来研究rhGH与PLA鼻腔联合给药作为一种新型递送系统的潜力。还通过尺寸排阻色谱法和超滤法评估了剂型中不溶性聚集体和可溶性复合物的形成对鼻腔rhGH吸收的影响。在所研究的每个浓度和分子量下，PLA均增强了rhGH的鼻腔吸收。当PLA浓度为1.0%（w/v）时，鼻腔rhGH吸收显著增加，这是由于rhGH在制剂中的溶解度提高。当PLA分子量增加时，观察到rhGH吸收延迟。这似乎是因为分子量的增加导致了可溶性复合物的形成。似乎PLA浓度影响对rhGH的吸收增强作用，而PLA分子量影响鼻腔给药后rhGH达到最大血浆浓度的时间（Tmax），主要是由于rhGH、PLA和添加剂之间的相互作用。因此，如果这些相互作用得到充分控制，使用PLA的经鼻rhGH递送系统被认为是皮下（s.c.）注射的一种有前途的替代方法。
