Enhanced oral absorption and therapeutic effect of acetylpuerarin based on D-α-tocopheryl polyethylene glycol 1000 succinate nanoemulsions

Abstract

Background Acetylpuerarin (AP), because of its lower water solubility, shows poor absorption that hinders its therapeutic application. Thus, the aim of this study was to prepare nanoemulsions for AP, enhance its oral bioavailability, and thus improve the therapeutic effect. Methods The nanoemulsions stabilized by D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) were prepared by high-pressure homogenization and characterized in terms of particle size, drug loading, morphology, and in vitro drug release. A lipid digestion model was used to predict in vivo drug solubilization in the gastrointestinal environment. The pharmacokinetics of AP formulations were performed in rats; meanwhile, a chylomicron flow-blocking rat model was used to evaluate the lymphatic drug transport. Moreover, the therapeutic effects of AP nanoemulsions on the model of focal cerebral ischemia-reperfusion for brain injury were also assessed. Results The nanoemulsions with a droplet size of 150 nm were well stabilized by TPGS and showed a high loading capacity for AP. In the digestion model, the distribution of AP in aqueous phase/pellet phase was about 90%/10% for nanoemulsions and 5%/95% for oil solution, indicating that the drug encapsulated in nanoemulsions would present in solubilized form after transportation into the gastrointestinal tract, whereas drug precipitation would occur as the oil solution was orally administered. The area under the curve value of AP nanoemulsions was 5.76±0.56 μg·hour·mL −1 , or was about 2.6 and 1.7 times as great as that of suspension and oil solution, respectively, indicating enhanced drug absorption and thus achieving a better neuroprotection effect on cerebral ischemic reperfusion injury. The values of peak plasma concentration and area under the curve from the blocking model were significantly less than those of the control model, suggesting that the lymphatic transport performed a very important role in absorption enhancement. Conclusion Enhanced oral bioavailability in nanoemulsions was achieved via the mechanism of the maintenance of drug solubilization in the gastrointestinal tract and the enhancement of lymphatic transport, which resulted in therapeutic improvement of cerebral ischemic reperfusion injury.

Recent Advances in the Application of Vitamin E TPGS for Drug Delivery

“…SEDDS/SMEDDS, an isotropic mixture composed of oil, solvent, surfactant and co-solvent/surfactant, can improve oral absorption of lipophilic drugs 141 . The TPGS stabilized acetylpuerarin nanoemulsions can increase drug solubilization in the gastrointestinal tract, improve lymphatic transport and thus enhance drug absorption for effective therapy on cerebral ischemic reperfusion injury 142 . In addition, microemulsions of BCS Class Ⅳ drug, cefpodoxime proxetil, were prepared by using Tween 80 and TPGS as surfactants and Capmul MCM as oil phase.…”

The effect of curcumin and its nanoformulation on adjuvant-induced arthritis in rats

“… 12 Fourth, Ns are easily fabricated and scaled-up; therefore, this is a promising technique for industrialization and application in the clinic. 13 , 14 Overall, Ns, with their ability to enhance solubility, stability, and bioavailability of drugs, are potent nanocarriers for oral delivery of insoluble drugs.…”

Sublingual Administration of Sildenafil Oro-dispersible Film: New Profiles of Drug Tolerability and Pharmacokinetics for PDE5 Inhibitors

“…We might then hypothesize that sub-lingual Sild absorption is favored by a prolonged drug-mucosa contact. Indeed, this phenomenon is generally pursued for oral trans-mucosal drugs, where the use of mucoadhesive polymers is recommended to assure prolonged period of contact between the formulation and the oral mucosa ( Lam et al, 2014 ), in particular from those drugs, like Sild, affected by low water solubility ( Zayed et al, 2012 ; Sun et al, 2014 ). These preliminary results are also suggestive of a possible improvement of the clinical efficacy for this class of drugs compared to original formulations.…”