Almutairy Bjad K, Alshetaili Abdullah, Alali Amer S, Ahmed Mohammed Muqtader, Anwer Md Khalid, Aboudzadeh M Ali
Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj 11942, Saudi Arabia.
Institut des Sciences Analytiques et de Physico-Chimie pour l'Environnement et les Matériaux, University Pau & Pays Adour, 64000 Pau, France.
Polymers (Basel). 2021 Jul 11;13(14):2272. doi: 10.3390/polym13142272.
Olmesartan medoxomil (OLM) is one of the prominent antihypertensive drug that suffers from low aqueous solubility and dissolution rate leading to its low bioavailability. To improve the oral bioavailability of OLM, a delivery system based on ethylcellulose (EC, a biobased polymer) nanosponges (NSs) was developed and evaluated for cytotoxicity against the A549 lung cell lines and antihypertensive potential in a rat model. Four OLM-loaded NSs (ONS1-ONS4) were prepared and fully evaluated in terms of physicochemical properties. Among these formulations, ONS4 was regarded as the optimized formulation with particle size (487 nm), PDI (0.386), zeta potential (ζP = -18.1 mV), entrapment efficiency (EE = 91.2%) and drug loading (DL = 0.88%). In addition, a nanosized porous morphology was detected for this optimized system with NS surface area of about 63.512 m/g, pore volume and pore radius Dv(r) of 0.149 cc/g and 15.274 Å, respectively, measured by nitrogen adsorption/desorption analysis. The observed morphology plus sustained release rate of OLM caused that the optimized formulation showed higher cytotoxicity against A549 lung cell lines in comparison to the pure OLM. Finally, this system (ONS4) reduced the systolic blood pressure (SBP) significantly ( < 0.01) as compared to control and pure OLM drug in spontaneously hypertensive rats. Overall, this study provides a scientific basis for future studies on the encapsulation efficiency of NSs as promising drug carriers for overcoming pharmacokinetic limitations.
奥美沙坦酯（OLM）是一种重要的抗高血压药物，但它的水溶性和溶解速率较低，导致其生物利用度较低。为了提高OLM的口服生物利用度，开发了一种基于乙基纤维素（EC，一种生物基聚合物）纳米海绵（NSs）的给药系统，并评估了其对A549肺癌细胞系的细胞毒性以及在大鼠模型中的抗高血压潜力。制备了四种载有OLM的NSs（ONS1-ONS4），并对其理化性质进行了全面评估。在这些制剂中，ONS4被认为是优化制剂，其粒径为487 nm，多分散指数（PDI）为0.386，zeta电位（ζP = -18.1 mV），包封率（EE = 91.2%）和载药量（DL = 0.88%）。此外，通过氮吸附/解吸分析检测到该优化系统具有纳米级多孔形态，NS表面积约为63.512 m/g，孔体积和孔径Dv(r)分别为0.149 cc/g和15.274 Å。观察到的形态加上OLM的缓释速率使得优化制剂与纯OLM相比，对A549肺癌细胞系表现出更高的细胞毒性。最后，与自发性高血压大鼠中的对照和纯OLM药物相比，该系统（ONS4）显著降低了收缩压（SBP）（<0.01）。总体而言，本研究为未来关于NSs作为有前景的药物载体克服药代动力学限制的包封效率研究提供了科学依据。
