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Objectives: Orientation to specific cells is an important topic in active targeting strategy for nanoparticle-based drug delivery systems. While these administered nanoparticles will be sequestrated within the liver, their cellular distribution behaviors in the liver are not clear. The aim of this study was to fabricate glycyrrhizic acid (GL) modified BSA nanoparticles and evaluate their hepatic cellular distribution. Methods: GL-modified BSA (GL-BSA) was tailored according to the periodate oxidation method, then GL-BSA nanoparticles loaded with paclitaxel (PTX@GL-BSA NPs) were prepared through self-assembly approach. In vitro cellular uptake was assessed by FITC-labeled BSA nanoparticles and immunofluorescent analysis was performed to track their relative distribution in the liver. Key findings: The fabricated PTX@GL-BSA NPs were spherical structure with the particle size of 179 nm and a negative potential (−17.3 mV). Flow cytometry (FCM) studies exhibited that the accumulation of GL-BSA nanoparticles was 5.3-fold compared with BSA nanoparticles in HepG2 cells. The Nanoparticles were preferentially accumulated in the sinusoidal endothelial cells rather than the Kupffer cells. Conclusions: This study provides useful information to understand the distribution of hepatic targeting nanoparticles when using GL-modified BSA nanoparticles, which helps to further use for effective treatment of liver disease. [ABSTRACT FROM AUTHOR]

Inspired by the fact that leukocytes have innate phagocytic functions and oriented migration capabilities in response to chemoattractants, we have unveiled that endogenous neutrophils as "Trojan horses", participate in the delivery of nanoparticles in an "in vivo self-armed assembly" manner. Neutrophils were the main population to preferentially sequester the intravenous administrated nanoparticles with an average size of 260 nm. The pre-implantation of CXCL1-laden hydrogels could trigger and induce a targeted signal to attract an influx of neutrophils carrying the therapeutic goods to the desired position. In mouse models of melanoma, the combinatorial regimen of using the PLGA nanoparticles with the CXCL1 hydrogels exhibited superior tumor inhibition capability. This work leveraged the natural phagocytosis of neutrophile and the chemotactic effect of chemokines for targeted delivery. We believe this strategy will improve the therapeutic efficiency of nanoparticle-based delivery systems, especially when the chemokines are implanted at sites of surgical tumor removal, during cancer treatment at the clinic. [ABSTRACT FROM AUTHOR]

Objective: To prepare oridonin nanoparticles and evaluate their pharmacokinetics in rats. Methods: The oridonin poly (lactic-co-glycolic acid) (PLGA) nanoparticles were prepared by emulsion sonication and solvent evaporation method with PLGA as encapsulation materials. Their physicochemical properties were identified through determination of particle size and polydispersity index (PDI), transmission electronic microscopy (TEM) observation of the appearance form, analysis of entrapment efficiency and drug loading. The oridonin PLGA nanoparticles were administered intravenously through caudal vein in rats. Then blood concentrations of oridonin were determined by HPLC method, and the pharmacokinetics were analyzed by DAS software. Results: The particle size of the prepared nanoparticles on the average was about 180 nm, the entrapment efficiency was (87.7 ± 7.7)% and drug loading was (7.5 ± 0.8)% with an outward spherical appearance. The compartment model was attrib-uted to two-compartment model after single intravenous injection of oridonin PLGA nanoparticles. The main pharmacokinetic parameters were as follows: half life of distribution phase (t1/2α) was 2.115 h, half life of elimination phase (t1/2β) was 69.315 h, the area under the curve (AUC) was 42.463 mg · h · L-1, clearance (CL) was 0.094 L · h-1 · kg-1, apparent volume of distribution (V) was 0.4 L/kg. Conclusion: The preparation technology of oridonin PLGA nanoparticles is simple and feasible, with a higher entrapment efficiency. The bioavailability of oridonin could be improved when oridonin was fabricated into PLGA nanoparticles. [ABSTRACT FROM AUTHOR]

A folic acid (FA)-functionalized drug vehicle platform based on Pluronic 127 (P127)/D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) mixed micelles was orchestrated for an effective delivery of the model drug resveratrol in order to address the problem of poor water solubility and rapid metabolism of resveratrol and improve its targeted accumulation at tumor site. The FA-decorated mixed micelles were prepared using thin-film hydration method and optimized by central composite design approach. The micelles were also characterized in terms of size and morphology, drug entrapment efficiency and in vitro release profile. In addition, the cytotoxicity and cell uptake of the micelles were evaluated in folate receptor-overexpressing MCF-7 cell line. In vivo pharmacokinetic and biodistribution studies were also performed. The average size of the micelles was ~20 nm with a spherical shape and high encapsulation efficiency (99.67%). The results of fluorescence microscopy confirmed the targeting capability of FA-conjugated micelles in MCF-7 cells. FA-modified micelles exhibited superior pharmacokinetics in comparison with that of solution. Further, the low accumulation of resveratrol-loaded FA micelles formulation in the heart and kidney avoided toxicity of these vital organs. It could be concluded that folate-modified P127/TPGS mixed micelles might serve as a potential delivery platform for resveratrol., Competing Interests: Disclosure The authors report no conflicts of interest in this work.