New zwitterionic HP-β-CD-PEI-MPC polymer used as a transdermal penetration enhancer

• Published in: Reactive & functional polymers Vol. 154; p. 104677
• Main Authors: Gao, Jushan, Zhao, Xiaoye, Jing, Wanghui, Zhang, Xinxin, Wang, Ke, Yan, Luke
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.09.2020; Elsevier BV
• Subjects: Cyanocobalamin; Cyclodextrins; Drug delivery systems; Enhancing ability; Evaluation; Fluorescence; Hydrophilicity; Irritation; Irritation of the skin; Michael reaction; NMR; Nuclear engineering; Nuclear magnetic resonance; Nuclear safety; Penetration; Phosphorylcholine; Polyethyleneimine; Polymers; Promoting mechanism; Raman spectroscopy; Ring opening; Spectrum analysis; Transdermal penetration enhancer; Vitamin B; Zwitterions; Transdermal penetration enhancer; Promoting mechanism; Enhancing ability; Irritation of the skin
• ISSN: 1381-5148; 1873-166X
• DOI: 10.1016/j.reactfunctpolym.2020.104677

In this study, a new kind of zwitterionic hydroxypropyl-β-cyclodextrin-polyethyleneimine grafted 2-methylallyloxyethyl phosphorylcholine (HP-β-CD-PEI1800-MPC) transdermal penetration enhancer was successfully synthesized, and its feasibility for promoting transdermal absorption of the hydrophilic drug Vitamin B12 was evaluated. The enhancer was synthesized by epoxy ring-opening and the Michael addition reaction, and its structure was confirmed by nuclear magnetic resonance spectrum (1HNMR). The penetration enhancing effect of HP-β-CD-PEI1800-MPC on hydrophilic vitamin B12 was evaluated by transdermal experience in vitro. A skin irritation experiment and histopathological observations of skin sections with hematoxylin and eosin (H&E) and Masson staining were performed to analyze the safety of HP-β-CD-PEI1800-MPC. A preliminary study was conducted on the promoting mechanism of the transdermal enhancer using laser Raman spectroscopy, ATR-FTIR and DSC. The transdermal depth and distribution of the enhancer in skin were examined by fluorescence labeling. In vitro transdermal permeation was determined by Franz cells, and the cumulative drug content through skin was measured by HPLC. All the data showed that HP-β-CD-PEI1800-MPC could be a safe and effective penetration enhancer for topical drug delivery. [Display omitted] •A new zwitterionic HP-β-CD-PEI-MPC polymers as the transdermal enhancer is prepared.•The transdermal mechanism of a new zwitterionic HP-β-CD-PEI-MPC polymers is explored.•The HP-β-CD-PEI-MPC polymer is safe and effective for transdermal delivery of Vitamin BThe HP-β-CD-PEI-MPC polymer is safe and effective for transdermal delivery of Vitamin B12.