Pluronic P123/L64 Mixed Micelles as Immediate Release Systems to Enhance the Bioavailability of Praziquantel in Rats

Pluronic P123/L64 混合胶束作为速释系统提高吡喹酮在大鼠体内的生物利用度

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Abstract

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

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