ABSTRACT
Nanoparticulate drug delivery systems (Nano-DDSs) have emerged as possible solution to the obstacles of anticancer drug delivery. However, the clinical outcomes and translation are restricted by several drawbacks, such as low drug loading, premature drug leakage and carrier-related toxicity. Recently, pure drug nano-assemblies (PDNAs), fabricated by the self-assembly or co-assembly of pure drug molecules, have attracted considerable attention. Their facile and reproducible preparation technique helps to remove the bottleneck of nanomedicines including quality control, scale-up production and clinical translation. Acting as both carriers and cargos, the carrier-free PDNAs have an ultra-high or even 100% drug loading. In addition, combination therapies based on PDNAs could possibly address the most intractable problems in cancer treatment, such as tumor metastasis and drug resistance. In the present review, the latest development of PDNAs for cancer treatment is overviewed. First, PDNAs are classified according to the composition of drug molecules, and the assembly mechanisms are discussed. Furthermore, the co-delivery of PDNAs for combination therapies is summarized, with special focus on the improvement of therapeutic outcomes. Finally, future prospects and challenges of PDNAs for efficient cancer therapy are spotlighted.
ABSTRACT
Erythrocytes (red blood cells, RBCs) are the most abundant circulating cells in the blood and have been widely used in drug delivery systems (DDS) because of their features of biocompatibility, biodegradability, and long circulating half-life. Accordingly, a "camouflage" comprised of erythrocyte membranes renders nanoparticles as a platform that combines the advantages of native erythrocyte membranes with those of nanomaterials. Following injection into the blood of animal models, the coated nanoparticles imitate RBCs and interact with the surroundings to achieve long-term circulation. In this review, the biomimetic platform of erythrocyte membrane-coated nano-cores is described with regard to various aspects, with particular focus placed on the coating mechanism, preparation methods, verification methods, and the latest anti-tumor applications. Finally, further functional modifications of the erythrocyte membranes and attempts to fuse the surface properties of multiple cell membranes are discussed, providing a foundation to stimulate extensive research into multifunctional nano-biomimetic systems.
ABSTRACT
Objective To evaluate the blood clearance,tissue uptake and distribution as well as safety of high dose-40 mg intravenous fish oil/'medium chain triglycerides (FO/MCT:2 ∶ 8,wt/wt) lipid emulsions iu mice by measuriug the contents of triglycerides (TG) and free fatty acids (FFA) level in blood.Methods FO/MCT emulsions were radiolabeled with nondegradable [3H] cholesteryl ether to trace core particle metabolism in C57BL/6J mice following a bolus injection.For high dose,TG was 40 mg,100 times of low dose.Blood samples were obtained within 25 min to analyze TG and FFA concentrations;extracted organs were used to measure the tissue distribution of lipid emulsions.Results No animal in either group died,and no fat overload syndrome evidence was found after high dose injection.Compared with low dose,high dose injection increased the plasma TG and FFA concentrations rapidly;the emulsions were cleared significantly slower during 25 min after administration in mice;blood has a higher uptake ratio in organs,but heart has a lower one;there was no significant difference in liver and lung uptake ratio between the two groups.Conclusions High dose injection of FO/MCT is not fatal in mice.The animals only experience hypertriglyceridemia and high level of free fatty acids during a significant slower blood clearance period compared to low dose.Although blood clearance is slower,the blood uptake rate increases for further metabolism and clearance.Heart and lung functions are not affected as a lower cardiac and pulmonary uptake;blood uptakes more emulsions to further metabolize.FO/MCT may not induce fat overload syndrome in mice when administered with a super high dose.