Sinha Swagata, Ravi Punna Rao, Rashmi Sahadevan Rajesh, Szeleszczuk Łukasz
Department of Pharmacy, Birla Institute of Technology and Science, Hyderabad Campus, Jawahar Nagar, Kapra Mandal, Medchal District, Pilani 500078, Telangana, India.
Department of Organic and Physical Chemistry, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Str., 02-093 Warsaw, Poland.
Pharmaceutics. 2025 Jun 13;17(6):774. doi: 10.3390/pharmaceutics17060774.
This research focuses on the development and optimization of polymer-lipid hybrid nanoparticles (PLHNs) using two grades of mPEG-PCL co-polymers in combination with DPPC and lecithin to address the biopharmaceutical challenges of acalabrutinib (ACP), a selective treatment for different hematological malignancies. : Variations in the mPEG-to-ε-caprolactone ratio influenced both the molecular weight (Mw) of the synthesized co-polymers and their aqueous phase affinity. The ACP-loaded PLHNs (ACP-PLHNs) were optimized using a circumscribed central composite design. The in vivo studies were performed in Wistar rats. : The lipophilic mPEG-PCL (Mw = 9817.67 Da) resulted in PLHNs with a particle size of 155.91 nm and 40.08% drug loading, while the hydrophilic mPEG-PCL (Mw = 23,615.84 Da) yielded PLHNs with a relatively larger size (223.46 nm) and relatively higher drug loading (46.59%). The drug release profiles were polymer-grade dependent: lipophilic ACP-PLHNs (ACP-PLHNs) sustained release up to 30 h in pH 7.2 buffer, while hydrophilic ACP-PLHNs (ACP-PLHNs) completed release within 24 h. Stability studies showed greater stability for ACP-PLHNs, likely due to reduced molecular rearrangement from the chemically stable lipophilic co-polymer. : Oral administration of both formulations exhibited a 2-fold ( < 0.001) improvement in the C and AUC and a 3.9-fold ( < 0.001) increase in the relatively oral bioavailability compared to the conventional ACP suspension in male wistar rats.
本研究聚焦于使用两种不同等级的甲氧基聚乙二醇-聚己内酯（mPEG-PCL）共聚物与二棕榈酰磷脂酰胆碱（DPPC）和卵磷脂相结合，来开发和优化聚合物-脂质杂化纳米颗粒（PLHNs），以应对阿卡替尼（ACP）这一针对不同血液系统恶性肿瘤的选择性治疗药物所面临的生物制药挑战。mPEG与ε-己内酯比例的变化影响了合成共聚物的分子量（Mw）及其水相亲和力。载有ACP的PLHNs（ACP-PLHNs）通过限定的中心复合设计进行了优化。体内研究在Wistar大鼠中进行。亲脂性的mPEG-PCL（Mw = 9817.67 Da）制得的PLHNs粒径为155.91 nm，载药量为40.08%，而亲水性的mPEG-PCL（Mw = 23615.84 Da）制得的PLHNs尺寸相对较大（223.46 nm），载药量相对较高（46.59%）。药物释放曲线取决于聚合物等级：亲脂性的ACP-PLHNs在pH 7.2缓冲液中可持续释放长达30小时，而亲水性的ACP-PLHNs在24小时内完成释放。稳定性研究表明ACP-PLHNs具有更高的稳定性，这可能是由于化学稳定的亲脂性共聚物减少了分子重排。与雄性Wistar大鼠中的传统ACP悬浮液相比，两种制剂的口服给药在C和AUC方面均有2倍的改善（<0.001），相对口服生物利用度提高了3.9倍（<0.001）。
