Khalid Hafiz Muhammad Bilal, Rasul Akhtar, Shah Shahid, Abbas Ghulam, Mahmood Abid
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad 38040, Pakistan.
Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad 38040, Pakistan.
ACS Omega. 2023 Mar 3;8(10):9662-9672. doi: 10.1021/acsomega.3c00400. eCollection 2023 Mar 14.
Most biopharmaceutics classification system (BCS) class IV drugs have limited oral bioavailability due to poor solubility and poorer permeability. This work aims to investigate the possibility of utilizing disulfide bridged nanoparticles to improve BCS IV drug solubility and oral absorption. Disulfide bridged nanoparticles were made using thiolated sodium alginate (TSA) and thiolated eudragit RS100 (TERS100). This study used paclitaxel (PTL) as a model drug to create PTL-loaded nanoparticles using the air oxidation approach. PTL-loaded nanoparticles boosted the solubility of PTL by over 11 times (∼59 μg/mL). The nanoparticles had particle sizes of 103 nm, polydispersity indices of 0.034, and zeta potentials of -21 mV, respectively. Nanoparticles demonstrated 75.34% and 89.18% entrapment and loading efficiency of PTL, respectively. The PTL release data from nanoparticles had good sustained release properties. The effective permeability of PTL from nanoparticles was 2.19-fold higher than that of pure PTL suspension. The relative bioavailability of PTL with disulfide bridged nanoparticles was 237.11%, which was much higher than that of PTL suspension, according to the pharmacokinetic data. These results show that disulfide bridged nanoparticles have a wide range of clinical applications.
大多数生物药剂学分类系统（BCS）IV类药物由于溶解度差和渗透性更差，口服生物利用度有限。本研究旨在探讨利用二硫键桥连纳米粒提高BCS IV类药物溶解度和口服吸收的可能性。使用硫醇化海藻酸钠（TSA）和硫醇化聚丙烯酸树脂RS100（TERS100）制备二硫键桥连纳米粒。本研究以紫杉醇（PTL）为模型药物，采用空气氧化法制备了载PTL纳米粒。载PTL纳米粒使PTL的溶解度提高了11倍以上（约59μg/mL）。纳米粒的粒径分别为103nm，多分散指数为0.034，ζ电位为-21mV。纳米粒对PTL的包封率和载药率分别为75.34%和89.18%。纳米粒的PTL释放数据具有良好的缓释性能。PTL从纳米粒的有效渗透率比纯PTL混悬液高2.19倍。根据药代动力学数据，二硫键桥连纳米粒的PTL相对生物利用度为237.11%，远高于PTL混悬液。这些结果表明二硫键桥连纳米粒具有广泛的临床应用前景。
