# Permeation Effect Analysis of Drug Using Raman Spectroscopy for Iontophoresis
###### Abstract  
Iontophoresis technology could improve the efficiency of transdermal drug delivery through the skin and be a promising prospective tool for clinical drug therapy in the near future. Surface-enhanced Raman spectroscopy (SERS) was used to analyze the concentration distribution of penicillin sodium in the skin of a mice model, and the iontophoresis delivery efficiency of drug percutaneous permeation was evaluated with various times and concentrations of penicillin sodium through Raman spectra. The results showed both the action time and drug concentration for iontophoresis can deeply influence transdermal drug delivery effects, and the Raman spectrum might be an effective method to evaluate transdermal drug delivery efficiency.  
iontophoresis; Raman spectrum; penicillin sodium; quantitative analysis +
Footnote †: journal:  
* [2022] 202220220220220220220202202022020220202202022020202202022020220202202022022020220220220220220220220220220220220220220220220220  
delivered as iontophoretic drugs in early studies. At present, more kinds of drugs are delivered by iontophoresis for improving treatment effects, such as ocular drugs [13], propranolol [14], biological macromolecular drugs [15], etc. Scars can be treated with iontophoresis, in which cathodal iontophoresis enhances the delivery of sodium fluorescein across the scar skin epidermis by approximately 46 folds, meaning iontophoresis could be utilized to overcome the barrier resistance of the scar skin epidermis and treat scars regionally [16]. Micro-needles or ultrasound have been combined with iontophoresis for the transdermal delivery of drugs [17; 18]. However, despite being a key index to evaluate the therapeutic effect of a drug, drug concentration in the skin is difficult to accurately measure. At the same time, some traditional methods are utilized to analyze the drug concentration on the skin, such as high-performance liquid chromatography (HPLC) [19] and mass spectrometry (MS) [20]. By using penicillin V as the internal standard, [PERSON] [21] developed and validated the method applied in the determination of amoxicillin and penicillin G (determined mean levels were 287/320 ng\(\cdot\)mL\({}^{-1}\)) and their major metabolites in bovine milk samples using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). However, these methods showed some limitations involving low sensitivity, time-consuming procedures, and complex sample preparation. Raman spectroscopy can provide information at the molecular level as a measurement and analysis method [22]. The intensities of Raman characteristic peaks are related to the concentrations of the corresponding molecules in samples [18; 23]. [PERSON] [24] detected the residue of penicillin G in milk using Raman spectroscopy with a detection limit of 0.85 ug\(\cdot\)kg\({}^{-1}\). It has been well-documented that Raman spectroscopy is suitable for the acquisition of qualitative permeation profiles [25], but a comprehensive investigation regarding its suitability for quantitative effect evaluations of drug iontophoresis permeation remains to be conducted.  
Based on all these premises, in this study, we explored the SERS method for quantitatively analyzing the influence of iontophoresis action time and drug concentration on the permeation effect for penicillin sodium.