Murugan E, Yogaraj V
Department of Physical Chemistry, School of Chemical Sciences, University of Madras, Guindy Campus, Chennai, Tamil Nadu, India.
Front Chem. 2023 Feb 17;11:1123775. doi: 10.3389/fchem.2023.1123775. eCollection 2023.
Furosemide (FRSD) is a loop diuretic that has been categorized as a class IV drug according to the Biopharmaceutics Classification System (BCS). It is used in the treatment of congestive heart failure and edema. Owing to low solubility and permeability, its oral bioavailability is very poor. In this study, two types of poly (amidoamine) dendrimer-based drug carriers (generation G2 and G3) were synthesized to increase the bioavailability of FRSD through solubility enhancement and sustained release. The developed dendrimers enhanced the solubility of FRSD 58- and 109-fold, respectively, compared with pure FRSD. studies demonstrated that the maximum time taken to release 95% of the drug from G2 and G3 was 420-510 min, respectively, whereas for pure FRSD the maximum time was only 90 min. Such a delayed release is strong evidence for sustained drug release. Cytotoxicity studies using Vero and HBL 100 cell lines through an MTT assay revealed increased cell viability, indicating reduced cytotoxicity and improved bioavailability. Therefore, the present dendrimer-based drug carriers are proven to be prominent, benign, biocompatible, and efficient for poorly soluble drugs, such as FRSD. Therefore, they could be convenient choices for real-time applications of drug delivery.
呋塞米（FRSD）是一种袢利尿剂，根据生物药剂学分类系统（BCS）被归类为IV类药物。它用于治疗充血性心力衰竭和水肿。由于其低溶解性和低渗透性，其口服生物利用度非常差。在本研究中，合成了两种基于聚（酰胺胺）树枝状大分子的药物载体（第2代和第3代），以通过提高溶解度和缓释来提高FRSD的生物利用度。与纯FRSD相比，所开发的树枝状大分子分别将FRSD的溶解度提高了58倍和109倍。研究表明，从G2和G3中释放95%药物的最长时间分别为420 - 510分钟，而对于纯FRSD，最长时间仅为90分钟。这种延迟释放是药物持续释放的有力证据。通过MTT法对Vero和HBL 100细胞系进行的细胞毒性研究显示细胞活力增加，表明细胞毒性降低且生物利用度提高。因此，目前基于树枝状大分子的药物载体被证明对于像FRSD这样的难溶性药物而言是突出的、良性的、生物相容的且高效的。因此，它们可能是药物递送实时应用的便捷选择。
