No abstract

Mangiferin (MGF) is found in many natural plants, such as Rhizoma Anemarrhenae, and has anti-diabetes effects. However, its clinical applications and development are limited by poor solubility and low-concentration enrichment in pancreatic islets. In this paper, targeted polymeric nanoparticles were constructed for MGF delivery with the desired drug loading content (6.86 ± 0.60%), excellent blood circulation, and missilelike delivery to the pancreas. Briefly, Glucagon-like peptide 1 (GLP-1) as an active targeting agent to the pancreas was immobilized on the block copolymer polyethyleneglycol-polycaprolactone (PEG-PCL) to obtain final GLP-1-PEG-PCL amphiphiles. Spherical MGF-loaded polymeric nanoparticles were acquired from the self-assembly of the targeted GDPP nanoparticles and MGF with a homogeneous size of 158.9 ± 1.7 nm and a negative potential for a good steady state in circulation. In this drug vehicle, GLP-1 acts as the missile vanguard via the GLP-1 receptor on the surface of the pancreas for improving the accumulation and efficiency of MGF in the pancreas, the hypoglycemic effect of MGF, and the restorative effect on pancreatic islets, which were investigated. As compared to free MGF, MGF/GDPP nanoparticles appeared to be more concentrated in the pancreas, with better blood glucose and glucose tolerance, enhanced insulin levels, increased β-cell proliferation, reduced β-cell apoptosis, and islet repair in vivo. This targeted drug delivery system provided a novel strategy and hope for enhancing MGF delivery and antidiabetes efficacy.

No abstract

Polymeric micelles are important carriers for anticancer drug delivery. However, rare papers focused on the dynamic of drug in the core of micelles. In this paper, we used fluorescence resonance energy transfer (FRET) technique to investigate the dynamic diffusion of drug from polymeric micelles. mPEG-PCL diblock copolymers were used as carriers. A pair of fluorescence molecules Cy3 and Cy5 was selected to evoke the FRET phenomenon. Cy5 was immobilized on the terminal group of PCL segments, Cy3 was encapsulated in the Cy5 modified polymeric micelles as the model drug. The drug loaded polymeric micelles were incubated with 4T1 breast cancer cells. The FRET was observed to explore the dynamic of Cy3 in the micelles. The results showed that the Cy3 loaded micelles were stable in aqueous solution as the energy-transfer efficiency (ETE, I660/I565) rarely decreased even when the time was as long as 120 h. The ETE increased with the content of encapsulated Cy3. The FRET spectra showed that the ETE of the Cy3 loaded polymeric micelles lowered with the release of Cy3 in PBS. The intracellular tracking of the Cy3 loaded micelles found more than 60% loaded drug was release within 12 h with the calculation of ETE in FRET spectra and it was same to confocal laser scanning and flow cytometry results.

Bio-inspired supramolecular self-assembly have been widely explored in biomedical engineering, especially in the field of drug delivery. Here, viral capsid analogue pH-Sensitive polymeric micelles HA-Hyd-DOX were reported, where natural polysacarrides hyaluronic acid (HA) and anticancer drug doxorubicin (DOX), were linked through a hydrazone bond with a high drug loading content of 33.09 wt%. The polymeric micelles look like artificial virus capsids from "core-shell" structures. In addition, the polymeric backbone HA and hydrazone bonds were destroyed in the presence of hyaluronidase in cancer cells and under the acidic conditions of pH = 5 respectively, thereby prodrug-based polymeric micelles could penetrate into the tumor and DOX could be released in lysosomes to enhance anticancer efficacy. With the comparison of typical prodrug-based polymeric micelles mPEG-Hyd-DOX system where DOX was linked to methoxy poly(ethylene glycol) with a hydrazone bond linkage, HA-Hyd-DOX showed greater inhibition to cancer cells due to the better penetration. Such viral capsids mimicking polymeric micelles provided some remarkable benefits for drug delivery, including, high drug loading efficiency, controlled drug release and excellent biodegradable.