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Investigation of the transport and absorption of Angelica sinensis polysaccharide through gastrointestinal tract both in vitro and in vivo.

ABSTRACT: To investigate the absorption and delivery of ASP in gastrointestinal (GI) tract, cASP was successfully synthesized by chemically modifying with succinic anhydride and then conjugating with a near infrared fluorescent dye Cy5.5. Then, the capacity of oral absorption of cASP was evaluated. The results demonstrated that cASP had low toxicity and no disruption on the integrity of cell membrane. The endocytosis of cASP into the epithelial cells was time- and energy-dependent, which was mediated by macropinocytosis pathway and clathrin- and caveolae (or lipid raft)-related routes. Otherwise, the actin filaments played a relatively weak role at the same time. The transport study illustrated that cASP could penetrate through the epithelial monolayer and mainly mediated by the same routes as that in the endocytosis experiment. Moreover, both in vitro Ussing chamber and in vivo ligated intestinal loops models indicated that cASP could be diffused through the mucus barriers and be absorbed in the whole small intestine. Finally, near-infrared fluorescence imaging presented that cASP could be absorbed and circulated into the blood, then distributed into various organs after oral administration. In conclusion, ASP could be absorbed after oral administration through endocytosis process mainly mediated by macropinocytosis pathway and clathrin- and caveolae (or lipid raft)-related routes, then be absorbed and circulated into blood. This study presents a comprehensive understanding of oral delivery of cASP, which will provide theoretical basis for the clinical application of ASP.

SUBMITTER: Wang K

PROVIDER: S-EPMC8240978 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:In vivo drug dissolution in the gastrointestinal (GI) tract is largely unmeasured. The purpose of this clinical study was to evaluate the in vivo drug dissolution and systemic absorption of the BCS class IIa drug ibuprofen under fed and fasted conditions by direct sampling of stomach and small intestinal luminal content. Expanding current knowledge of drug dissolution in vivo will help to establish physiologically relevant in vitro models predictive of drug dissolution. A multilumen GI catheter was orally inserted into the GI tract of healthy human subjects. Subjects received a single oral dose of ibuprofen (800 mg tablet) with 250 mL of water under fasting and fed conditions. The GI catheter facilitated collection of GI fluid from the stomach, duodenum, and jejunum. Ibuprofen concentration in GI fluid supernatant and plasma was determined by LC-MS/MS. A total of 23 subjects completed the study, with 11 subjects returning for an additional study visit (a total of 34 completed study visits). The subjects were primarily white (61%) and male (65%) with an average age of 30 years. The subjects had a median [min, max] weight of 79 [52, 123] kg and body mass index of 25.7 [19.4, 37.7] kg/m2. Ibuprofen plasma levels were higher under fasted conditions and remained detectable for 28 h under both conditions. The AUC0-24 and Cmax were lower in fed subjects vs fasted subjects, and Tmax was delayed in fed subjects vs fasted subjects. Ibuprofen was detected immediately after ingestion in the stomach under fasting and fed conditions until 7 h after dosing. Higher levels of ibuprofen were detected in the small intestine soon after dosing in fasted subjects compared to fed. In contrast to plasma drug concentration, overall gastric concentrations remained higher under fed conditions due to increased gastric pH vs fasting condition. The gastric pH increased to near neutrality after feedingbefore decreasing to acidic levels after 7 h. Induction of the fed state reduced systemic levels but increased gastric levels of ibuprofen, which suggest that slow gastric emptying and transit dominate the effect for plasma drug concentration. The finding of high levels of ibuprofen in stomach and small intestine 7 h post dosing was unexpected. Future work is needed to better understand the role of various GI parameters, such as motility and gastric emptying, on systemic ibuprofen levels in order to improve in vitro predictive models.

Dataset Information

Investigation of the transport and absorption of Angelica sinensis polysaccharide through gastrointestinal tract both in vitro and in vivo.

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