Erythrocyte Membrane-Coated Arsenic Trioxide-Loaded Sodium Alginate Nanoparticles for Tumor Therapy.

Arsenic trioxide (ATO) has a significant effect on the treatment of acute promyelocytic leukemia (APL) and advanced primary liver cancer, but it still faces severe side effects. Considering these problems, red blood cell membrane-camouflaged ATO-loaded sodium alginate nanoparticles (RBCM-SA-ATO-NPs, RSANs) were developed to relieve the toxicity of ATO while maintaining its efficacy. ATO-loaded sodium alginate nanoparticles (SA-ATO-NPs, SANs) were prepared by the ion crosslinking method, and then RBCM was extruded onto the surface to obtain RSANs. The average particle size of RSANs was found to be 163.2 nm with a complete shell-core bilayer structure, and the average encapsulation efficiency was 14.31%. Compared with SANs, RAW 264.7 macrophages reduced the phagocytosis of RSANs by 51%, and the in vitro cumulative release rate of RSANs was 95% at 84 h, which revealed a prominent sustained release. Furthermore, it demonstrated that RSANs had lower cytotoxicity as compared to normal 293 cells and exhibited anti-tumor effects on both NB4 cells and 7721 cells. In vivo studies further showed that ATO could cause mild lesions of main organs while RSANs could reduce the toxicity and improve the anti-tumor effects. In brief, the developed RSANs system provides a promising alternative for ATO treatment safely and effectively.

Preparation and Characterization of Erythrocyte Membrane-Camouflaged Berberine Hydrochloride-Loaded Gelatin Nanoparticles.

The discovery of a new pharmacological application of berberine hydrochloride (BH) made it more clinically valuable. However, the further development of BH was hampered by its short half-life and side effects after intravenous injection. To overcome these problems, a novel BH delivery system was developed using natural red blood cell membrane-camouflaged BH-loaded gelatin nanoparticles (RBGPs) to reduce the toxicity associated with injections and achieve sustained release. The size of the RBGPs was 260.3 ± 4.1 nm, with an obvious core⁻shell structure, and the membrane proteins of the RBGPs were mostly retained. The RBGP system showed significant immune-evading capabilities and little cytotoxicity to human embryonic kidney (HEK) 293T cells and LO2 cells. Finally, RBGPs improved the sustained releasing effect of BH significantly. When the cumulative release time reached 120 h, the cumulative release rate of RBGPs was 78.42%. In brief, RBGPs hold the potential to achieve long circulation and sustained-release of BH, avoid side effects caused by high plasma concentration in common injection formulations, and broaden the clinical applications of BH.

Er Shen Wan extract alleviates polyuria and regulates AQP 2 and AVPR 2 in a rat model of spleen-kidney Yang deficiency-induced diarrhea.

ETHNOPHARMACOLOGICAL RELEVANCE: Er Shen Wan (ESW), has been empirically used for treating spleen-kidney Yang deficiency (SKYD) syndrome in Traditional Chinese medicine (TCM) for centuries and shows a variety of activities. The medicinal formula is a mixture of two component herbs, Psoraleae Fructus (PF, Bu-Gu-Zhi in Chinese) and Myristicae Semen (MS, Rou-Dou-Kou in Chinese). The current study was designed to evaluate ESWP antidiuretic treatment of polyuria and to explore potential mechanisms of renal water metabolism in the rat model of SKYD-induced diarrhea. MATERIALS AND METHODS: An animal model of 'SKYD-induced diarrhea syndrome' has been established to evaluate the therapeutic effect and action mechanism according to the clinical syndrome and symptoms. The optimal dose (3.5 g/kg) of ESWP was given to rats by gavage for two weeks. Urinary volumes after 24 h were recorded. After the end of the trial, macroscopic morphological and histological examination of the kidney were conducted. Serum levels of Arginine vasopressin (AVP) and aldosterone (ALD) were also measured. Additionally, quantitative real-time RT-PCR (RT-qPCR) and immunohistochemistry (IHC) analyses were performed to clarify the regulation of aquaporin 2 (AQP 2) and arginine vasopressin type 2 receptor (AVPR 2) in the kidney at the gene and tissue expression levels respectively. RESULTS: After the administration of ESWP, urinary output volume after 24 h was found to be significantly decreased in rats. Elevated plasma levels of AVP and ALD were detected. Histological kidney damage appeared to be impeded, and histological disease scores were reduced. In addition, the expression levels of AQP 2 and AVPR 2 were significantly increased. CONCLUSION: This study suggests that ESWP may elicit significant effects on the treatment of polyuria. Potential mechanisms at least partially involve hormone regulation, and alleviating renal pathological damage. Simultaneously, ESWP may alter renal water absorption by increasing AQP 2 and AVPR 2 expression levels. Thus, the in vivo experimental evidence indicates that ESWP has a therapeutic effect on the SKYD syndrome, which is consistent with its traditional usage.

Autologous Red Blood Cell Delivery of Betamethasone Phosphate Sodium for Long Anti-Inflammation.

Although glucocorticoids are highly effective in treating various types of inflammation such as skin disease, rheumatic disease, and allergic disease, their application have been seriously limited for their high incidence of side effects, particularly in long term treatment. To improve efficacy and reduce side effects, we encapsulated betamethasone phosphate (BSP) into biocompatible red blood cells (RBCs) and explored its long acting-effect. BSP was loaded into rat autologous erythrocytes by hypotonic preswelling method, and the loading amount was about 2.5 mg/mL cells. In vitro, BSP loaded RBCs (BSP-RBCs) presented similar morphology, osmotic fragility to native RBCs (NRBCs). After the loading process, the loaded cells can maintain around 70% of Na⁺/K⁺-ATPase activity of natural cells. In vivo, a series of tests including survival, pharmacokinetics, and anti-inflammatory effect were carried out to examine the long-acting effect of BSP-RBCs. The results shown that the loaded cells could circulate in plasma for over nine days, the release of BSP can last for over seven days and the anti-inflammatory effect can still be observed on day 5 after injection. Totally, BSP-loaded autologous erythrocytes seem to be a promising sustained releasing delivery system with long anti-inflammatory effect.

Nanocrystals Technology for Pharmaceutical Science.

BACKGROUND: Nanocrystals technology is a promising method for improving the dissolution rate and enhancing the bioavailability of poorly soluble drugs. In recent years, it has been developing rapidly and applied to drug research and engineering. Nanocrystal drugs can be formulated into various dosage forms. OBJECTIVE: This review mainly focused on the nanocrystals technology and its application in pharmaceutical science. Firstly, different preparation methods of nanocrystal technology and the characterization of nanocrystal drugs are briefly described. Secondly, the application of nanocrystals technology in pharmaceutical science is mainly discussed followed by the introduction of sustained release formulations. Then, the scaling up process, marketed nanocrystal drug products and regulatory aspects about nanodrugs are summarized. Finally, the specific challenges and opportunities of nanocrystals technology for pharmaceutical science are summarized and discussed. CONCLUSION: This review will provide a comprehensive guide for scientists and engineers in the field of pharmaceutical science and biochemical engineering.

Preparation and characterization of erythrocyte membrane cloaked PLGA/arsenic trioxide nanoparticles and evaluation of their in vitro anti-tumor effect.

Arsenic trioxide (ATO) is used for acute promyelocytic leukemia (APL) that is resistant to all-trans-retinoic acid, but its direct intravenous injection sometimes induces severe toxic side effects. Here, we developed a delivery system of red blood cell membrane (RBCM) cloaked poly (lactic-co-glycolic) acid (PLGA)-ATO nanoparticles (RPANs) to reduce the toxicity. PLGA was used to entrap the ATO, and the PLGA-ATO nanoparticles (PANs) were prepared by the emulsification method. Then RBCMs were employed to cloak the PANs using ultrasonication, to develop the RPANs delivery system. The prepared RPANs had a uniform size of around 233.6 nm with an obvious core-shell structure, as observed by TEM. The completeness of the membrane proteins was confirmed by SDS-PAGE and an in vitro release time of 65 h was determined for the RPANs. The RPANs also exhibited low cytotoxicity against the 293k kidney cell line (84.6% cell viability rate), which suggested that the ATO toxicity was reduced by RBCM cloaking. Moreover, the anti-tumor effects of the RPANs against the HL60 cell line were comparable to those of ATO solution. Our study demonstrated that the RPANs system has anti-tumor potential and could be developed into a safe and sustained release delivery system for ATO.