Strategies to release doxorubicin from doxorubicin delivery vehicles.

Doxorubicin (DOX) is one of the most effective cytotoxic anticancer drugs and has been successfully applied in clinics to treat haematological malignancies and a broad range of solid tumours. However, the clinical applications of DOX have long been limited due to severe dose-dependent toxicities. Recent advances in the development of DOX delivery vehicles have addressed some of the non-specific toxicity challenges associated with DOX. These DOX-loaded vehicles are designed to release DOX in cancer cells effectively by cutting off linkers between DOX and carriers response to stimuli. This article focuses on various strategies that serve as potential tools to release DOX from DOX-loaded vehicles efficiently to achieve a higher DOX concentration in tumour tissue and a lower concentration in normal tissue. With a deeper understanding of the differences between normal and tumour tissues, it might be possible to design ever more promising prodrug systems for DOX delivery and cancer therapy in the near future.

A review of polypeptide-based polymersomes.

Self-assembled systems from biodegradable amphiphilic polymers at the nanometer scale, such as nanotubes, nanoparticles, polymer micelles, nanogels, and polymersomes, have attracted much attention especially in biomedical fields. Among these nano-aggregates, polymersomes have attracted tremendous interests as versatile carriers due to their colloidal stability, tunable membrane properties and ability of encapsulating or integrating a broad range of drugs and molecules. Biodegradable block polymers, especially aliphatic polyesters such as polylactide, polyglycolide and poly (ε-caprolactone) have been widely used as biomedical materials for a long time to well fit the requirement of biomedical drug carriers. To have a precise control of the aggregation behavior of nano-aggregates, the more ordered polypeptide has been used to self-assemble into the drug carriers. In this review we focus on the study of polymersomes which also named pepsomes formed by polypeptide-based copolymers and attempt to clarify the polypeptide-based polymersomes from following aspects: synthesis and characterization of the polypeptide-based copolymers, preparation, multifunction and application of polypeptide-based polymersomes.

Self-assembly properties, aggregation behavior and prospective application for sustained drug delivery of a drug-participating catanionic system.

In the present study, the self-assembly properties, aggregation behavior and potential application of mixed samples formed by an active drug (diclofenac sodium, DS) and conventional surfactant (didodecyldimethyl ammonium bromide, DDAB) are investigated with surface tension, transmission electron microscope (TEM), dynamic light scattering (DLS), zeta potential, conductivity, in vitro drug release and hemolytic toxicity measurements. The physicochemical parameters such as critical micelle concentration (CMC), the surface tension at CMC (γCMC), the maximum surface excess concentration (Γ max) and the minimum area per molecule headgroup at the air/water interface (A min) and degree of counterion binding (ß) are obtained from the surface tension and electrical conductivity measurements. The results show that diclofenac sodium can decrease the surface tension of water and aggregate in the aqueous solution when its concentration is large enough. The CMC and γCMC of the DS/DDAB mixed systems are found to have values between that of individual DS and DDAB solutions. TEM and DLS results demonstrate the formation of spherical vesicles in a wide range of the molar ratio of the two components. The amount of charge on the vesicles and their stability can be tuned by controlling the amount of drug and surfactant. To evaluate the potential use of the as-prepared DS/DDAB catanionic vesicles in drug delivery systems, the in vitro drug release and hemolytic toxicity are carried out. The results indicate that both the drug release behavior and the hemolytic toxicity are dependent on the composition of the samples, X1 (X1=nDS/n(DS+DDAB), decreasing with the decrease of X1. The results of this work suggested that the drug-participating catanionic vesicles can be used as a safe and an efficient vehicle for sustained drug release.

Folate-conjugated hybrid SBA-15 particles for targeted anticancer drug delivery.

Surface functionalization is one of the key steps toward the utilization of mesoporous materials in drug delivery system. Here, the folic acid (FA) ligands are conjugated onto poly(ethylene imine) (PEI) modified SBA-15 particles (PEI/SBA-15) via amide reaction, which results in the FA/PEI/SBA-15 particles. Doxorubicin hydrochloride (DOX), an anticancer drug, is successfully loaded into these particles. The in vitro cytotoxicity and cellular uptake of the empty FA/PEI/SBA-15 particles and the DOX-loaded ones are evaluated on two kinds of cancer cells (HeLa cells and A549 cells). Specifically, an excellent cellular uptake using the current anticancer drug delivery vehicles (DOX-loaded FA/PEI/SBA-15 particles) mediated by the FA receptor is demonstrated by fluorescence microscope and flow cytometry. The FA/PEI/SBA-15 particles demonstrate a lower cytotoxicity comparing with the PEI/SBA-15 particles, while the DOX-loaded FA/PEI/SBA-15 particles exhibit much greater inhibition to the studied cancer cells. Furthermore, the in vitro release study shows that the targeted FA/PEI/SBA-15 particles have a typical sustained release behavior. This work therefore demonstrates that drug-loaded FA/PEI/SBA-15 particles have great potential application in targeted anticancer drug delivery for cancer therapy.

Formation of drug/surfactant catanionic vesicles and their application in sustained drug release.

The aggregation behavior of the cationic drug/anionic surfactant vesicles formed by tetracaine hydrochloride (TH) and double-chain surfactant, sodium bis(2-ethylhexyl)sulfosuccinate (AOT), was investigated. By controlling the molar ratio of TH to AOT, a transition from catanionic vesicles to micelles was observed. The catanionic aggregates exhibited different charge properties, structures, interaction enthalpies and drug release behaviors depending on the composition. To characterize the cationic drug/anionic surfactant system, transmission electron microscopy (TEM), dynamic light scattering (DLS), isothermal titration calorimetry (ITC), conductivity, turbidity and zeta potential (ζ) measurements were performed. The drug release results indicate that the present drug-containing catanionic vesicles have promising applications in drug delivery systems. Furthermore, the percentage of drug distributed in the catanionic vesicles or micelles can be obtained by comparing the cumulative release of the corresponding aggregates with the pure drug solution.