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Improvement of pulmonary absorption of poorly absorbable macromolecules by hydroxypropyl-β-cyclodextrin grafted polyethylenimine (HP-β-CD-PEI) in rats.
Int J Pharm. 2015 Jul 15; 489(1-2):294-303.IJ

Abstract

Effects of hydroxypropyl-β-cyclodextrin grafted polyethylenimine (HP-β-CD-PEI) including HP-β-CD-PEI600, HP-β-CD-PEI1800, HP-β-CD-PEI10000 on the pulmonary absorption of insulin, calcitonin, 5(6)-carboxyfluorescein (CF) and fluorescein isothiocyanate dextrans (FDs) with various molecular weights (FD4, FD10 and FD70) were examined by an pulmonary absorption study in rats. Pulmonary absorptions of these poorly absorbable drugs were significantly enhanced by HP-β-CD-PEI1800 and HP-β-CD-PEI10000, and HP-β-CD-PEI1800 with the concentration of 5% (w/v) provided maximal absorption enhancing effect on pulmonary absorption of these model drugs. The toxicity study demonstrated that HP-β-CD-PEI did not induce any toxic action to rat pulmonary membranes. In addition, zeta potential of insulin solution changed to positive by addition of various HP-β-CD-PEI, meanwhile, the degree of positive charge was linearly correlated with absorption enhancing effect of HP-β-CD-PEI, suggesting that positive charge of HP-β-CD-PEI might be related to their absorption enhancing mechanisms for enhancing pulmonary absorption of insulin in rats. In conclusion, HP-β-CD-PEI is a potential and safe absorption enhancer for improving absorption of hydrophilic macromolecules especially peptide and protein drugs by pulmonary delivery.

Authors+Show Affiliations

School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.National TCM Key Lab of Serum Pharmacochemistry, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin, China.School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.School of Pharmacy, Xi'an Jiaotong University, Xi'an, China. Electronic address: gaoyangyang@mail.xjtu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25959121

Citation

Zhang, Hailong, et al. "Improvement of Pulmonary Absorption of Poorly Absorbable Macromolecules By Hydroxypropyl-β-cyclodextrin Grafted Polyethylenimine (HP-β-CD-PEI) in Rats." International Journal of Pharmaceutics, vol. 489, no. 1-2, 2015, pp. 294-303.
Zhang H, Huang X, Sun Y, et al. Improvement of pulmonary absorption of poorly absorbable macromolecules by hydroxypropyl-β-cyclodextrin grafted polyethylenimine (HP-β-CD-PEI) in rats. Int J Pharm. 2015;489(1-2):294-303.
Zhang, H., Huang, X., Sun, Y., Lu, G., Wang, K., Wang, Z., Xing, J., & Gao, Y. (2015). Improvement of pulmonary absorption of poorly absorbable macromolecules by hydroxypropyl-β-cyclodextrin grafted polyethylenimine (HP-β-CD-PEI) in rats. International Journal of Pharmaceutics, 489(1-2), 294-303. https://doi.org/10.1016/j.ijpharm.2015.05.020
Zhang H, et al. Improvement of Pulmonary Absorption of Poorly Absorbable Macromolecules By Hydroxypropyl-β-cyclodextrin Grafted Polyethylenimine (HP-β-CD-PEI) in Rats. Int J Pharm. 2015 Jul 15;489(1-2):294-303. PubMed PMID: 25959121.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Improvement of pulmonary absorption of poorly absorbable macromolecules by hydroxypropyl-β-cyclodextrin grafted polyethylenimine (HP-β-CD-PEI) in rats. AU - Zhang,Hailong, AU - Huang,Xiaoyan, AU - Sun,Ya, AU - Lu,Guangyou, AU - Wang,Ke, AU - Wang,Zhigang, AU - Xing,Jianfeng, AU - Gao,Yang, Y1 - 2015/05/07/ PY - 2014/12/30/received PY - 2015/04/16/revised PY - 2015/05/06/accepted PY - 2015/5/12/entrez PY - 2015/5/12/pubmed PY - 2016/3/2/medline KW - HP-β-CD-PEI KW - Membrane toxicity KW - Poorly absorbable drugs KW - Pulmonary absorption SP - 294 EP - 303 JF - International journal of pharmaceutics JO - Int J Pharm VL - 489 IS - 1-2 N2 - Effects of hydroxypropyl-β-cyclodextrin grafted polyethylenimine (HP-β-CD-PEI) including HP-β-CD-PEI600, HP-β-CD-PEI1800, HP-β-CD-PEI10000 on the pulmonary absorption of insulin, calcitonin, 5(6)-carboxyfluorescein (CF) and fluorescein isothiocyanate dextrans (FDs) with various molecular weights (FD4, FD10 and FD70) were examined by an pulmonary absorption study in rats. Pulmonary absorptions of these poorly absorbable drugs were significantly enhanced by HP-β-CD-PEI1800 and HP-β-CD-PEI10000, and HP-β-CD-PEI1800 with the concentration of 5% (w/v) provided maximal absorption enhancing effect on pulmonary absorption of these model drugs. The toxicity study demonstrated that HP-β-CD-PEI did not induce any toxic action to rat pulmonary membranes. In addition, zeta potential of insulin solution changed to positive by addition of various HP-β-CD-PEI, meanwhile, the degree of positive charge was linearly correlated with absorption enhancing effect of HP-β-CD-PEI, suggesting that positive charge of HP-β-CD-PEI might be related to their absorption enhancing mechanisms for enhancing pulmonary absorption of insulin in rats. In conclusion, HP-β-CD-PEI is a potential and safe absorption enhancer for improving absorption of hydrophilic macromolecules especially peptide and protein drugs by pulmonary delivery. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/25959121/Improvement_of_pulmonary_absorption_of_poorly_absorbable_macromolecules_by_hydroxypropyl_β_cyclodextrin_grafted_polyethylenimine__HP_β_CD_PEI__in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(15)00439-1 DB - PRIME DP - Unbound Medicine ER -