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Approximately 30% of the world's land area is acidic soil (pH < 5.5), and aluminum (Al) toxicity and phosphorus (P) deficiency are two main constraints of plant growth in acidic soil. However, direct application of P fertilizer to acidic soil can form insoluble Al–P precipitates, thus reducing P availability. We used a split-root technique to experimentally investigate whether Eucalyptus seedlings can translocate P from root halves with no Al stress to root halves experiencing Al stress, thus ameliorating the Al toxicity of the latter. The results revealed that P application led to fixation of Al in the form of an Al–P precipitate in sand, thus relieving Al toxicity. In addition, the application of P increased the nutritive P supply and alleviated P deficiency within the plant. In Eucalyptus seedlings, increased P application to the root half without Al3+ exposure alleviated Al toxicity in the other root half. The extent of resistance to Al stress depended on the genotype of the Eucalyptus seedlings. Based on our findings, P can be applied to areas not only through roots, but also by other methods, such as leaf fertilization or application of nutrient solutions to the trunk, preferably avoiding the formation of Al–P precipitates in the soil. [ABSTRACT FROM AUTHOR]

The key structural requirement for the antitumor activity of 10-hydroxycamptothecin (HCPT) is the intact lactone moiety which is always instability and suffered from pH-dependent hydrolysis. The aim of this study was to evaluate the protection effects of liposomal encapsulation on the labile lactone ring. Mono-modal dispersed quasi-spherical liposomes with mean diameter of 145 nm and high drug entrapment efficiency of 90% were obtained under optimal conditions. The in vitro hydrolysis kinetics behaviors of lactone were studied in varied pH buffers. Compared to that of free HCPT in solution formulation, both the hydrolysis half-life and observed equilibrium constant of liposomal HCPT were increased significantly along with the decreased apparent hydrolysis rate constant. The plasma pharmacokinetics was studied by assessing the lactone stability versus time profiles in vivo following intravenous administration of free and liposomal HCPT. The liposomal encapsulation led to a twofold increase in the AUC values and significant decrease in the plasma clearance of lactone ( P < 0.05). There was a good correlation between in vitro and in vivo stability of HCPT-lactone. These results suggested a potential application of the novel liposome formulation for the stable delivery system of HCPT. [ABSTRACT FROM AUTHOR]

Objective: This study presents a preliminary exploration on extending the half-life of therapeutic proteins by crystallization strategy without new molecular entities generation. Methods: Recombinant human interferon (rhIFN) α-2b, a model protein drug in this case, was crystallized using a hanging-drop vapor diffusion method. A novel chelating technique with metal ions was employed to promote crystals formation. Results: The effects of key factors such as seeding protein concentration, pH of the hanging drop, ionic strength of the equilibration solution, and precipitants were investigated. Size-exclusion liquid chromatography, antiviral activity determination, and enzyme-linked immunosorbent assay indicated that both the molecular integrity and biological potency of rhIFN were not significantly affected by crystallization process. In addition, the in vitro release behavior of rhIFN from crystal lattice was characterized by an initial fast release, followed by a sustained release up to 48 hour. Conclusion: The work described here suggested an exciting possibility of therapeutic protein crystals as a long-acting formulation. [ABSTRACT FROM AUTHOR]

Despite its strong anti-tumor activity against human cancers, paclitaxel (Taxol®) suffers limited clinical applications due to the low aqueous solubility and lack of appropriate delivery vehicles. In an attempt to develop an alternative formulation of paclitaxel suitable for parenteral administration, paclitaxel-loaded lipid nanospheres were constructed as colloidal carrier system for controlled drug delivery. Alpha-tocopheryl succinate ( α-TOS), a semi-synthetic vitamin E analog, was employed as a new physiological acceptable lipid material to prepare nanoparticulates. A novel bottom-up process was performed by a modified spontaneous emulsification solvent-diffusion method, which is suitable for large industrial scale production. The influence of key parameters such as temperature and surfactant concentration on the size and uniformity of the distribution of nanospheres were investigated. Spherical particles with ∼ 100 nm of mean diameter and 90% of drug entrapment efficiency were obtained under optimal conditions. Physicochemical characterization of the particles reveals a molecular dispersion of paclitaxel in the lipidic matrix. The in vitro release behavior of paclitaxel from the developed nanospheres was characterized by an initial fast release, followed by a sustained release up to 72 h. The release mechanism suggests that paclitaxel release from the vehicles was dual controlled by both the diffusion of drug and corrosion of lipid matrix. These results demonstrate the principle suitability of α-TOS-based lipid nanospheres as a potential delivery system for paclitaxel delivery. [ABSTRACT FROM AUTHOR]