A natural polysaccharide-based nanogel has been synthesized and characterized as pH-sensitive drug delivery system for poorly water-soluble anticancer drugs. In this work, methacrylated hyaluronic acid (MAHA) was used to prepared acid degradable nanogels by a surfactant-free polymerization method in water, where 2,2-dimethacroyloxy-1-ethoxypropane (DMAEP) served as a pH labile cross-linker. Nanogels of different cross-linking density were prepared and doxorubicin (DOX) was successfully encapsulated into the nanogels with drug-loading contents (DLC) ranging from 7.67 to 12.15%. An accelerated DOX release was found in acidic conditions. Cytotoxicity study showed that the DOX loaded nanogels have significantly enhanced cytotoxicity in vitro compared with the nonsensitive ones. Confocal microscopy revealed that there was more DOX in the nuclei of tumor cells when incubated with DOX-loaded pH sensitive nanogels for 3 to 12 h. The enhanced anticancer activity of DOX-loaded pH-sensitive nanogels was also verified by in vivo therapeutic study on mice, in which tumor volume evolution was measured and tumor tissues cell apoptosis and proliferation was examined.

In this study, the structure–activity relationship of amphiphilic block copolymer micelles as nanosized drug delivery system was revealed. Firstly, a biodegradable triblock polymers PEG-DiHyd-PLA containing hydrazone bond was synthesized through the ring-opening polymerization. In this method, PEG-DiHyd-Phenol was used as the initiator and L-lactide as the monomer. Then, the polymeric micelles were formed and used as nano-drug carriers with pH sensitivity. The structure and composition of the polymer were characterized by infrared (IR), nuclear magnetic resonance (1H-NMR), and gel permeation chromatography (GPC), we characterized the self-assembling process of the triblock polymers and the pH sensitivity of the micelles by the means of transmission electron microscopy (TEM), dynamic light scattering method (DLS). Doxorubicin (DOX) acts as the model drug, and we researched the capacities of drug loading and release in vitro of the micelles. MTT experiments showed that the blank micelles of PEG-DiHyd-PLA were not cytotoxic to tumor cells (HepG-2, MCF-7) and normal cell (L-02 cells), but the DOX loaded ones displayed more toxicity than the ones without hydrazone, which was consistent to the further confocal laser scanning microscopy and flow cytometry study.

Coenzyme Q (CoQ) is widely used in preventive or curative treatment of cardiovascular diseases. However, CoQ exhibits an extremely low solubility in aqueous medium as well as a poor oral bioavailability. Therefore, solanesyl poly(ethylene glycol) succinate (SPGS) and CoQ were formulated as CoQ-SPGS micelles with a high content of CoQ to improve the bioavailability of CoQ in rat. Findings indicate that, in the CoQ-SPGS micelles, SPGS is self-assembled into stable nanosized micelles with a CoQ loading capacity of more than 39%. The CoQ-SPGS micelles exhibit an enhanced photostability upon exposure to simulated sunlight. In vivo experiments demonstrate that, as compared to that of the coarse suspensions of CoQ, there was three-fold enhancement of oral bioavailability for CoQ-loaded SPGS micelles depending on varying molecular weight of SPGS. In the encapsulation of CoQ by SPGS micelles, the self-assembled nanocarriers with strong muco-adhesive properties lead to increases in the solubility and oral absorption of lipophilic CoQ nanoparticles.

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