Vigato Aryane A, Machado Ian P, Del Valle Matheus, da Ana Patricia A, Sepulveda Anderson F, Yokaichiya Fabiano, Franco Margareth K K D, Loiola Messias C, Tófoli Giovana R, Cereda Cintia Maria S, de Sairre Mirela I, de Araujo Daniele R
Human and Natural Sciences Center, Federal University of ABC, Sao Paulo 09210-580, SP, Brazil.
Department of Fundamental Chemistry, Institute of Chemistry, University of São Paulo, Sao Paulo 05508-000, SP, Brazil.
Pharmaceutics. 2022 Jan 27;14(2):293. doi: 10.3390/pharmaceutics14020293.
Organogels (ORGs) are remarkable matrices due to their versatile chemical composition and straightforward preparation. This study proposes the development of ORGs as dual drug-carrier systems, considering the application of synthetic monoketonic curcuminoid (m-CUR) and lidocaine (LDC) to treat topical inflammatory lesions. The monoketone curcuminoid (m-CUR) was synthesized by using an innovative method via a NbCl-acid catalysis. ORGs were prepared by associating an aqueous phase composed of Pluronic F127 and LDC hydrochloride with an organic phase comprising isopropyl myristate (IPM), soy lecithin (LEC), and the synthesized m-CUR. Physicochemical characterization was performed to evaluate the influence of the organic phase on the ORGs supramolecular organization, permeation profiles, cytotoxicity, and epidermis structural characteristics. The physico-chemical properties of the ORGs were shown to be strongly dependent on the oil phase constitution. Results revealed that the incorporation of LEC and m-CUR shifted the sol-gel transition temperature, and that the addition of LDC enhanced the rheological G'/G″ ratio to higher values compared to original ORGs. Consequently, highly structured gels lead to gradual and controlled LDC permeation profiles from the ORG formulations. Porcine ear skin epidermis was treated with ORGs and evaluated by infrared spectroscopy (FTIR), where the stratum corneum lipids were shown to transition from a hexagonal to a liquid crystal phase. Quantitative optical coherence tomography (OCT) analysis revealed that LEC and m-CUR additives modify skin structuring. Data from this study pointed ORGs as promising formulations for skin-delivery.
有机凝胶（ORGs）因其多样的化学成分和简单的制备方法而成为引人注目的基质。本研究提出将ORGs开发为双药物载体系统，考虑应用合成单酮姜黄素类化合物（m-CUR）和利多卡因（LDC）治疗局部炎症性病变。单酮姜黄素类化合物（m-CUR）通过一种创新方法经NbCl-酸催化合成。通过将由普朗尼克F127和盐酸利多卡因组成的水相与包含肉豆蔻酸异丙酯（IPM）、大豆卵磷脂（LEC）和合成的m-CUR的有机相相结合来制备ORGs。进行了物理化学表征，以评估有机相对ORGs超分子结构、渗透曲线、细胞毒性和表皮结构特征的影响。结果表明，ORGs的物理化学性质强烈依赖于油相组成。结果显示，LEC和m-CUR的加入改变了溶胶-凝胶转变温度，并且与原始ORGs相比，LDC的加入使流变学G'/G″比值提高到更高值。因此，高度结构化的凝胶导致LDC从ORG制剂中逐渐且可控地渗透。用ORGs处理猪耳皮肤表皮并通过红外光谱（FTIR）进行评估，结果显示角质层脂质从六方相转变为液晶相。定量光学相干断层扫描（OCT）分析表明，LEC和m-CUR添加剂改变了皮肤结构。本研究的数据表明ORGs是有前景的皮肤给药制剂。
