Yuan Jing, Su Wenhao, Gao Jingyang, Ma Xiaoqing, Yin Ronghuan, Jia Tong
Key Laboratory of Livestock Infectious Diseases, Ministry of Education, and Key Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, 110866, People's Republic of China.
College of Information Science and Engineering, Northeastern University, Shenyang, 110819, People's Republic of China.
Int J Nanomedicine. 2025 Jul 7;20:8861-8871. doi: 10.2147/IJN.S520910. eCollection 2025.
Praziquantel (PZQ) is currently the preferred medication for treating various parasites. However, its use is hindered by several issues, such as poor solubility, first-pass effect, and individual variability. A novel immediate release system was developed by loading PZQ onto Pluronic P123/L64 mixed micelles (PMMs). This approach aims to improve its bioavailability following oral administration.
PZQ-PMMs were prepared by thin film dispersion method. The encapsulation efficiency (EE), particle size, and polydispersity index (PDI) were utilized to identify the optimal formulation. Characterization techniques, including electron microscopy, infrared spectroscopy, thermal analysis, and X-ray diffraction were utilized to get an understanding of the molecular interactions between PZQ and micelles. This system was compared with commercially available preparations both in vitro and in vivo.
The particle size of the prepared PZQ-PMMs (P123:L64 1:1, w/w) was 19.33 ± 0.22 nm, with a PDI value of 0.106 ± 0.044, an EE of 86.88 ± 4.60%, and a drug loading of 4.16 ± 0.21%. Structural characterization results indicated that the spherical micelles were uniformly dispersed, with the drug existing in an amorphous form within PMMs. In vitro, PZQ-PMMs exhibited a faster immediate release in both pH 1.2 and pH 6.8 buffers. In vivo, at the same dosage, the micelles rapidly produced higher blood drug concentrations. The relative bioavailability of PZQ-PMMs was comparable to that of the PZQ 30% ethanol solution and was 1.7 times greater than that of commercially available preparations, with the increase in bioavailability being highly significant (P < 0.01).
The findings of this study confirm that Pluronic P123/L64 PMMs represent a novel and promising approach for enhancing solubility and bioavailability of PZQ, both in vitro and in vivo. The development of immediate release formulations is anticipated to be an effective option for drugs exhibiting a notable first-pass effect.
吡喹酮（PZQ）是目前治疗多种寄生虫的首选药物。然而，其应用受到一些问题的阻碍，如溶解度差、首过效应和个体差异。通过将PZQ负载到普朗尼克P123/L64混合胶束（PMMs）上开发了一种新型速释系统。该方法旨在提高其口服后的生物利用度。
采用薄膜分散法制备PZQ-PMMs。利用包封率（EE）、粒径和多分散指数（PDI）来确定最佳配方。采用电子显微镜、红外光谱、热分析和X射线衍射等表征技术来了解PZQ与胶束之间的分子相互作用。该系统在体外和体内均与市售制剂进行了比较。
制备的PZQ-PMMs（P123:L64 1:1，w/w）粒径为19.33±0.22nm，PDI值为0.106±0.044，EE为86.88±4.60%，载药量为4.16±0.21%。结构表征结果表明，球形胶束均匀分散，药物以无定形形式存在于PMMs中。在体外，PZQ-PMMs在pH 1.2和pH 6.8缓冲液中均表现出更快的速释。在体内，在相同剂量下，胶束迅速产生更高的血药浓度。PZQ-PMMs的相对生物利用度与PZQ 30%乙醇溶液相当，比市售制剂高1.7倍，生物利用度的提高具有高度显著性（P<0.01）。
本研究结果证实，普朗尼克P123/L64 PMMs是一种在体外和体内提高PZQ溶解度和生物利用度的新型且有前景的方法。速释制剂的开发有望成为具有显著首过效应药物的有效选择。
