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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.

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.

To enhance the water solubility, oral bioavailability, and tumor targeting of gambogenic acid (GNA), polydopamine nanoparticles (PDA NPs) were prepared to encapsulate and stabilize GNA surface modified by folic acid (FA) and then coated with sodium alginate (GNA@PDA-FA SA NPs) to achieve an antitumor effect by oral administration. GNA@PDA-FA SA NPs exhibited in vitro pH-sensitive release behavior. In vitro cell studies manifested that GNA@PDA-FA NPs had higher cytotoxicity to 4T1 cells compared with raw GNA (IC 50 = 2.58 μM vs 7.57 μM). After being modified with FA, GNA@PDA-FA NPs were taken up easily by 4T1 cells. In vivo studies demonstrated that the area under the curve (AUC 0→∞ ) of the plasma drug concentration−time of GNA@ PDA-FA SA NPs was 2.97-fold higher than that of raw GNA, along with improving drug distribution in the liver, lung, and kidney tissues. In vivo anti-tumor experiments, GNA@PDA-FA SA NPs significantly inhibited the growth of breast tumors in the 4T1 xenograft breast cancer model via oral administration without obvious toxicity on major organs. Our studies indicated that the GNA@PDA-FA SA NPs modified with FA and coated with SA were a promising drug delivery system for targeting tumor therapy via oral administration.

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.