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

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.