Rhamnose-PEG-induced supramolecular helices: Addressing challenges of drug solubility and release efficiency in transdermal patch

• Published in: Journal of controlled release 2024-03, Vol.367, p.848-863
• Main Authors: Song, Haoyuan, Liu, Chao, Ruan, Jiuheng, Cai, Yu, Wang, Jiaqi, Wang, Xiaoxu, Fang, Liang
• Format: Article
• Language: English
• Subjects: Drug solubility; Release efficiency; Rhamnose; Supramolecular; Transdermal drug delivery systems
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2024.02.016

Transdermal drug delivery systems (TDDS) demand both high drug loading capacity and efficient delivery. In order to improve both simultaneously, this study aims to develop a novel rhamnose-induced pressure-sensitive adhesive (HPR) by dispersing the drug in the supramolecular helical structure. Ten model drugs, categorized as acidic and basic compounds, were chosen to understand the characteristics of the HPR and its inner mechanism. Notably, it enhanced drug loading by 1.41 to 5 times over commercially available pressure-sensitive adhesives Duro-Tak@ 87–4098 and Duro-Tak@ 87–2287, in addition to increasing drug release efficiency by a factor of about 5. Pharmacokinetic evaluation demonstrated that the HPR group had >4-fold (Tulobuterol TUL) and 3-fold (Diclofenac DIC) more area under the blood drug concentration curve (AUC) than the commercial TUL and DIC patches in the absence of added excipients and a significantly prolonged mean residence time (MRT) of >4-fold (TUL) and 3-fold (DIC), demonstrating the potential for highly efficacious and prolonged dosing. Furthermore, its safety and mechanical properties meet the requisite standards. Mechanistic inquiries unveiled that both acidic and basic drugs establish hydrogen bonds with HPR and become encapsulated within supramolecular helical structures. The supramolecular helical structures, significantly elevated both the enthalpy of the drug-HPR and entropy of the drugs release, thereby substantially enhancing drug delivery efficiency. In summary, HPR enabled a significant simultaneous enhancement of drug loading and drug delivery, which, together with its unique spatial structure, would contribute to the development of TDDS. In addition, the establishment of rhamnose-induced supramolecular helical structures would provide innovative pathways for different drug delivery systems. [Display omitted]