Preparation and intestinal absorption mechanism of herpetrione and Herpetospermum caudigerum polysaccharides based self-assembled nanoparticles
In this experiment,self-assembled nanoparticles(SANs)were prepared by the pH-driven method,and Her-HCP SAN was constructed by using herpetrione(Her)and Herpetospermum caudigerum polysaccharides(HCPs).The average particle size and polydispersity index(PDI)were used as evaluation indexes for process optimization,and the quality of the final formulation was evaluated in terms of particle size,PDI,Zeta potential,and microstructure.The proposed Her-HCP SAN showed a spheroid structure and uniform morphology,with an average particle size of(244.58±16.84)nm,a PDI of 0.147 1±0.014 8,and a Zeta potential of(-38.52±2.11)mV.Her-HCP SAN significantly increased the saturation solubility of Her by 2.69 times,with a cumulative release of 90.18％within eight hours.The results of in vivo unidirectional intestinal perfusion reveal that Her active pharmaceutical ingredient(API)is most effectively absorbed in the jejunum,where both Ka and Papp are significantly higher compared to the ileum(P＜0.001).However,the addition of HCP leads to a significant reduction in the Papp of Her in the jejunum(P＜0.05).Furthermore,the formation of the Her-HCP SAN results in a notably lower Papp in the jejunum compared to Her API alone(P＜0.001),while both Ka and Papp in the ileum are significantly increased(P＜0.001,P＜0.05).The absorption of Her-HCP SAN at different concentrations in the ileum shows no significant differences,and the pH has no significant effect on the absorption of Her-HCP SAN in the ileum.The addition of the transporter protein inhibitors(indomethacin and rifampicin)significantly increases the absorption parameters Ka and Papp of Her-HCP SAN in the ileum(P＜0.05,P＜0.01),whereas the addition of verapamil has no significant effect on the intestinal absorption parameters of Her-HCP SAN,suggesting that Her may be a substrate for multidrug resistance-associated protein 2 and breast cancer resistance proteins but not a substrate of P-glycoprotein.
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维普
