International journal of pharmaceutics · 2026
The solid dispersion of a novel curcumin analogue (CACN136) prepared using PVP/Mannitol composite carrier significantly improved oral bioavailability and depression-like behavior in mice.
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Wei Yumeng, Gong Ke, Li Rongzhu, Zhang Qiong, Zhong Yueting, Zhao Wenmei, Zuo Ying, Chue Shifeng, Zhao Ling
Аннотация
OBJECTIVE: CACN136 is a novel curcumin analogue with antidepressant potential, but its poor aqueous solubility may restrict oral absorption. This study aimed to develop a rapidly dissolving solid dispersion of CACN136 (CACN136-SD) to further enhance its oral bioavailability and antidepressant efficacy.
METHODS: CACN136-SD was prepared using a solvent method with PVP and mannitol as composite carriers. Physicochemical characterization was performed through in vitro experiments, followed by pharmacokinetic and antidepressant behavioral evaluations.
RESULTS: CACN136-SD increased the apparent aqueous solubility of CACN136 approximately 20-fold. Cumulative dissolution at 10 min reached 95.69%, versus 6.64% for the active pharmaceutical ingredient (API). Differential scanning calorimetry and X-ray powder diffraction showed markedly reduced drug crystallinity, with CACN136 present predominantly in an amorphous or highly disordered state within the carrier matrix. Fourier-transform infrared spectroscopy showed changes in the local vibrational environment of CACN136 after incorporation into the matrix. The apparent terminal half-life of CACN136-SD was approximately 23 times that of the API, and its systemic exposure (AUC-t) was 8.95 times higher. In the chronic unpredictable mild stress (CUMS) model, CACN136-SD significantly alleviated depression-like behaviors and produced greater changes in serum and hippocampal 5-hydroxytryptamine (5-HT) and monoamine oxidase (MAO) levels than unformulated CACN136. Preliminary safety assessments detected no obvious cardiac, hepatic, or renal toxicity under the tested conditions.
CONCLUSION: CACN136-SD improved the solubility, dissolution, and oral exposure of CACN136 and showed enhanced antidepressant-like activity associated with changes in monoamine-related markers. This solid dispersion represents a promising antidepressant candidate with potential for clinical translation.
METHODS: CACN136-SD was prepared using a solvent method with PVP and mannitol as composite carriers. Physicochemical characterization was performed through in vitro experiments, followed by pharmacokinetic and antidepressant behavioral evaluations.
RESULTS: CACN136-SD increased the apparent aqueous solubility of CACN136 approximately 20-fold. Cumulative dissolution at 10 min reached 95.69%, versus 6.64% for the active pharmaceutical ingredient (API). Differential scanning calorimetry and X-ray powder diffraction showed markedly reduced drug crystallinity, with CACN136 present predominantly in an amorphous or highly disordered state within the carrier matrix. Fourier-transform infrared spectroscopy showed changes in the local vibrational environment of CACN136 after incorporation into the matrix. The apparent terminal half-life of CACN136-SD was approximately 23 times that of the API, and its systemic exposure (AUC-t) was 8.95 times higher. In the chronic unpredictable mild stress (CUMS) model, CACN136-SD significantly alleviated depression-like behaviors and produced greater changes in serum and hippocampal 5-hydroxytryptamine (5-HT) and monoamine oxidase (MAO) levels than unformulated CACN136. Preliminary safety assessments detected no obvious cardiac, hepatic, or renal toxicity under the tested conditions.
CONCLUSION: CACN136-SD improved the solubility, dissolution, and oral exposure of CACN136 and showed enhanced antidepressant-like activity associated with changes in monoamine-related markers. This solid dispersion represents a promising antidepressant candidate with potential for clinical translation.