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Objectives Zein nanoparticles (Zein NPs) were used as a hydroxyapatite (HA) biomineralization template to generate HA/Zein NPs. Doxorubicin hydrochloride (DOX) was loaded on HA/Zein NPs (HA/Zein‐DOX NPs) to improve its pH‐sensitive release, bioavailability and decrease cardiotoxicity. Methods HA/Zein‐DOX NPs were prepared by phase separation and biomimetic mineralization method. Particle size, polydispersity index (PDI), Zeta potential, transmission electron microscope, X‐ray diffraction and Fourier‐transform infrared spectroscopy of HA/Zein‐DOX NPs were characterized. The nanoparticles were then evaluated in vitro and in vivo. Key findings The small PDI and high Zeta potential demonstrated that HA/Zein‐DOX NPs were a stable and homogeneous dispersed system and that HA was mineralized on Zein‐DOX NPs. HA/Zein‐DOX NPs showed pH‐sensitive release. Compared with free DOX, HA/Zein‐DOX NPs increased cellular uptake which caused 7 times higher in‐vitro cytotoxicity in 4T1 cells. Pharmacokinetic experiments indicated the t1/2β and AUC0–t of HA/Zein‐DOX NPs were 2.73‐ and 3.12‐fold higher than those of DOX solution, respectively. Tissue distribution exhibited HA/Zein‐DOX NPs reduced heart toxicity with lower heart targeting efficiency (18.58%) than that of DOX solution (37.62%). Conclusion In this study, HA/Zein‐DOX NPs represented an antitumour drug delivery system for DOX in clinical tumour therapy with improved bioavailability and decreased cardiotoxicity.

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Objectives Gambogenic acid (GNA), one of the main active ingredients isolated from Garcinia cambogia, has shown diverse antitumour activities. However, short biological half‐life and low oral bioavailability severely limit its clinical application. Here, we developed GNA‐loaded zein nanoparticles (GNA‐ZN‐NPs) based on phospholipid complex and zein nanoparticles to prolong the circulation time and enhance oral bioavailability of GNA. Methods The physicochemical properties of GNA‐ZN‐NP were characterized in details. The in vitro release profile, in vivo pharmacokinetic experiments and tissue distribution of GNA‐ZN‐NPs were also evaluated. Key findings The particle size, PDI and encapsulation efficiency of GNA‐ZN‐NPs were 102.90 nm, 0.027 and 76.35 ± 0.64%, respectively. The results of SEM, FTIR, DSC and XRD demonstrated that GNA‐ZN‐NPs were prepared successfully. The in vitro dissolution of GNA‐ZN‐NPs exhibited controlled release compared with raw GNA solution. The pharmacokinetic study showed that the AUC of GNA‐ZN‐NPs was significantly increased, and the t1/2 and MRT values of GNA‐ZN‐NPs were 3.21‐fold and 2.19‐fold higher than that of GNA solution. Tissue distribution results illustrated that GNA‐ZN‐NPs showed hepatic‐targeting properties. Conclusion GNA‐ZN‐NPs significantly enhanced the oral bioavailability and prolonged half‐life of GNA, providing a promising oral drug delivery system to improve in vivo pharmacokinetic behaviour of GNA.

Objectives Resveratrol (Res), a naturally occurring polyphenol, has shown pharmacological activities in treatment of liver diseases. However, the application of Res was limited by its poor bioavailability and liver targeting. Herein, 3‐O‐β‐D‐Galactosylated Resveratrol (Gal‐Res) was synthesized by structural modification of Res to enhance bioavailability and liver targeting. Methods The Gal‐Res was characterized by IR, 1H‐NMR spectra and MS. The in vitro antitumour experiments, in vivo pharmacokinetics and biodistribution studies were evaluated. Results Gal‐Res was successfully synthesized in our study. Compared to Res, Gal‐Res resulted in enhanced cytotoxicity in HepG2 cells. After intravenous injection of normal SD rats, Gal‐Res significantly improved the bioavailability of Res and the Cmax and AUC0–t of Gal‐Res were 3.186 and 3.929 time than that of Res. In addition, in the study of liver targeting, the relative uptake rate (Re) of Gal‐Res in the liver (2.006) is the largest. The drug targeting efficiency (Te; 38.924%) of Gal‐Res was greater than that of Res. These showed that Gal‐Res could significantly improve the distribution ability of Res in liver. Conclusions On the whole, Gal‐Res increased cellular uptake to HepG2 cells, bioavailability and liver targeting, providing its future clinical application in the treatment of liver diseases.

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Nanosuspensions technique is an important tool to enhance the saturation solubility and dissolution velocity of poorly soluble drugs. Trans-resveratrol (t-Res) with extensive pharmacological effects was severely restricted by poor solubility and short biological half-life. In this study, anti-solvent precipitation was employed to development trans-resveratrol nanosuspensions (t-Res NS) with PVPK30 as stabilizer. The physicochemical properties, in vitro release and in vivo pharmacokinetics of t-Res NS were investigated. The mean particle size, zeta potential, encapsulation efficiency and drug loading of t-Res NS prepared by the optimal prescription were 96.9 nm, -20.4mV, 78% and 28.1%, respectively. The morphology of t-Res nanoparticles was spherical indicated by SEM with amorphous phase verified by XRD and DSC. The t-Res NS present a good physical stability as well as enhanced chemical stability. Compared to crude drug, the in vitro dissolution rate of t-Res NS was increased with fitting Higuchi equation (Q=0.3215t1/2+0.0070). The in vivo pharmacokinetic test in rats showed that the AUC0∼t of t-Res NS (559.4 μg/mL·min) was about 3.6-fold higher than that of t-Res solution. Meanwhile, the MRT of t-Res nanosuspensions was longer than that of t-Res solution. These results suggested that NS may be a potentially nanocarrier for clinical delivery of t-Res.