Construction of multi-program responsive vitamin E succinate-chitosan-histidine nanocarrier and its response strategy in tumor therapy.

Multifunctional drug delivery carriers have emerged as a promising cancer drug delivery strategy. Here, we developed a vitamin E succinate-chitosan-histidine (VCH) multi-program responsive drug carrier. The structure was characterized by FT-IR and 1H NMR spectrum, and the DLS and SEM results showed typical nanostructures. The drug loading content was 21.0 % and the corresponding encapsulation efficiency was 66.6 %. The UV-vis and fluorescence spectra demonstrated the existence of the π-π stacking interaction between DOX and VCH. Drug release experiments implied good pH sensitivity and sustained-release effect. The DOX/VCH nanoparticles could be efficiently taken up by HepG2 cancer cells and the tumor inhibition rate was up to 56.27 %. The DOX/VCH reduced the tumor volume and weight efficiently with a TIR of 45.81 %. The histological analysis results showed that DOX/VCH could effectively inhibit tumor growth and proliferation, and there was no damage to normal organs. VCH nanocarriers could combine the advantages of VES, histidine and chitosan to achieve pH sensitivity and P-gp inhibition, and effectively improve the drug solubility, targeting and lysosomal escape. Through the program response of different micro-environment, the newly developed polymeric micelles could successfully be utilized as a multi-program responsive nanocarrier system for the treatment of cancers.

Recent Advances and Progress on Melanin: From Source to Application.

Melanin is a biological pigment formed by indoles and phenolic compounds. It is widely found in living organisms and has a variety of unique properties. Due to its diverse characteristics and good biocompatibility, melanin has become the focus in the fields of biomedicine, agriculture, the food industry, etc. However, due to the wide range of melanin sources, complex polymerization properties, and low solubility of specific solvents, the specific macromolecular structure and polymerization mechanism of melanin remain unclear, which significantly limits the further study and application of melanin. Its synthesis and degradation pathways are also controversial. In addition, new properties and applications of melanin are constantly being discovered. In this review, we focus on the recent advances in the research of melanin in all aspects. Firstly, the classification, source, and degradation of melanin are summarized. Secondly, a detailed description of the structure, characterization, and properties of melanin is followed. The novel biological activity of melanin and its application is described at the end.

pH-sensitive O-carboxymethyl chitosan/sodium alginate nanohydrogel for enhanced oral delivery of insulin.

Oral drug delivery is considered the most preferred mode of treatment because of its high patient compliance and minimal invasiveness. However, the oral delivery of protein drug has been a difficult problem which restricts its application due to the unstable and inefficient penetration of protein in the gastrointestinal tract. In this study, a novel OCMC/SA nanohydrogel was prepared by using of O-carboxymethyl chitosan (OCMC) and sodium alginate (SA) to solve the problem. The OCMC/SA had a typical nanostructure, which was helpful to increase the specific surface area and enhanced the bioavailability of the drugs. OCMC/SA had a high drug loading capacity and realized passive drug targeting function by responding to the different pH value of the microenvironment. It could have a certain protective effect on drugs in strong acid circumstances, while its structure got loosed and effectively released drugs in intestinal circumstances. OCMC/SA could release the drug for >12 h, and the released insulin could maintain high activity. OCMC/SA nanohydrogel showed promising results in type 1 diabetic rats, and its pharmacological bioavailability was 6.57 %. In conclusion, this study constructed a novel OCMC/SA nanohydrogel, which had a lot of exciting characteristics and provided a new strategy for oral drug delivery.

N-carboxymethyl chitosan/sodium alginate composite hydrogel loading plasmid DNA as a promising gene activated matrix for in-situ burn wound treatment.

Improving the degree of vascularization through the regulation of wound microenvironment is crucial for wound repair. Gene activated matrix (GAM) technology provides a new approach for skin regeneration. It is a local gene delivery system that can not only maintain a moist environment, but also increase the concentration of local active factors. For this purpose, we fabricated the mVEGF165/TGF-ß1 gene-loaded N-carboxymethyl chitosan/sodium alginate hydrogel and studied its effect on promoting deep second degree burn wound repair. The average diameter of the hydrogel pores was 100 µm and the porosity was calculated as 50.9%. SEM and CLSM images showed that the hydrogel was suitable for cell adhesion and growth. The NS-GAM could maintain continuous expression for at least 9 days in vitro, showing long-term gene release and expression effect. Deep second-degree burn wound model was made on the backs of Wistar rats to evaluate the healing effect. The wounds were healed by day 22 in NS-GAM group with the prolonged high expression of VEGF and TGF-ß1 protein. A high degree of neovascularization and high expression level of CD34 were observed in NS-GAM group in 21 days. The histological results showed that NS-GAM had good tissue safety and could effectively promote epithelialization and collagen regeneration. These results indicated that the NS-GAM could be applied as a promising local gene delivery system for the repair of deep second-degree burn wounds.