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基于低共熔凝胶的药物递送:阿替洛尔给药的创新方法。

Eutectogel-Based Drug Delivery: An Innovative Approach for Atenolol Administration.

作者信息

Cassano Roberta, Sole Roberta, Siciliano Carlo, Baldino Noemi, Mileti Olga, Procopio Debora, Curcio Federica, Calviello Gabriella, Serini Simona, Trombino Sonia, Di Gioia Maria Luisa

机构信息

Dipartimento di Farmacia, Salute e Scienze della Nutrizione, Università della Calabria, Arcavacata di Rende, 87036 Cosenza, Italy.

Dipartimento di Ingegneria Informatica, Modellistica, Elettronica e Sistemistica, Università della Calabria, Arcavacata di Rende, 87036 Cosenza, Italy.

出版信息

Pharmaceutics. 2024 Dec 4;16(12):1552. doi: 10.3390/pharmaceutics16121552.

Abstract

Hypertension affects 32% of adults worldwide, leading to a significant global consumption of cardiovascular medications. Atenolol, a β-adrenergic receptor blocker, is widely prescribed for cardiovascular diseases such as hypertension, angina pectoris, and myocardial infarction. According to the Biopharmaceutics Classification System (BCS), atenolol belongs to Class III, characterized by high solubility but low permeability. Currently, atenolol is commercially available in oral formulations. Increasing attention is being directed towards developing cost-effective transdermal delivery systems, due to their ease of use and better patient compliance. Eutectogels represent next-generation systems that are attracting great interest in the scientific community. Typically obtained from deep eutectic solvents (DESs) combined with gelling agents, these systems exhibit unique properties due to the intrinsic characteristics of DESs. In this study, a DES based on choline chloride as a hydrogen bond acceptor (HBA) and propylene glycol as a hydrogen bond donor (HBD) was explored to enhance the topical delivery of atenolol. The solubility of atenolol in the DES was evaluated using spectroscopic and thermodynamic measurements which confirmed the formation of hydrogen bonds between the drug and DES components. Additionally, the safety of the DES was assessed in a cell viability assay. Subsequently, we formulated eutectogels with different concentrations using animal gelatin and Tego Carbomer 140, and characterized these formulations through rheological measurements, swelling percentage, and permeation studies with Franz cells. These novel eutectogels exhibit superior performance over conventional hydrogels, with a release rate of approximately 86% and 51% for Carbomer- and gelatin-based eutectogels, respectively. In contrast, comparable hydrogels released only about 27% and 35%. These findings underscore the promising potential of eutectogels for the transdermal delivery of atenolol.

摘要

高血压影响着全球32%的成年人,导致全球心血管药物的大量消耗。阿替洛尔是一种β-肾上腺素能受体阻滞剂,被广泛用于治疗高血压、心绞痛和心肌梗死等心血管疾病。根据生物药剂学分类系统(BCS),阿替洛尔属于III类药物,其特点是高溶解性但低渗透性。目前,阿替洛尔有口服制剂上市。由于其使用方便且患者依从性更好,开发具有成本效益的透皮给药系统正受到越来越多的关注。低共熔凝胶代表了新一代系统,在科学界引起了极大的兴趣。这些系统通常由低共熔溶剂(DESs)与胶凝剂组合而成,由于DESs的内在特性而具有独特的性能。在本研究中,探索了一种以氯化胆碱作为氢键受体(HBA)和丙二醇作为氢键供体(HBD)的DES,以增强阿替洛尔的局部给药。使用光谱和热力学测量方法评估了阿替洛尔在DES中的溶解度,证实了药物与DES成分之间形成了氢键。此外,在细胞活力测定中评估了DES的安全性。随后,我们使用动物明胶和Tego Carbomer 140配制了不同浓度的低共熔凝胶,并通过流变学测量、溶胀率和使用Franz扩散池的渗透研究对这些制剂进行了表征。这些新型低共熔凝胶表现出优于传统水凝胶的性能,基于Carbomer和明胶的低共熔凝胶的释放率分别约为86%和51%。相比之下,类似的水凝胶仅释放约27%和35%。这些发现强调了低共熔凝胶在阿替洛尔透皮给药方面的潜在应用前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16c2/11728620/35ee6dc96a65/pharmaceutics-16-01552-g001.jpg

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