Optimization on conditions of podophyllotoxin-loaded liposomes using response surface methodology and its activity on PC3 cells.

The purpose of this study was to optimize the preparation conditions of podophyllotoxin liposomes (PPT-Lips), and to investigate their effects on PC3 cells. PPT-Lips were prepared by using a thin-film dispersion method. In order to achieve maximum drug encapsulation efficiency (EE), the process and formulation variables were optimized by response surface methodology (RSM). The optimum preparation conditions were cholesterol to lecithin ratio of 3.6:40 (w/w), lipid to drug ratio of 15.8:1 (w/w), and the ultrasonic intensity of 35% (total power of 400 W). The experimental EE of PPT-Lips was 90.425%, which was consistent with the theoretically predicted value. The characterization studies showed that PPT-Lips were well-dispersible spherical particles with an average size of 106 nm and a zeta potential of -10.1 mV. A gradual and time-dependent pattern of PPT from liposomes was found in in vitro drug release with a cumulative release amount up to 70.3% in 24 h. Results of cell viability experiments on PC3 cells demonstrated that PPT-Lips exhibited more effective anticancer activity in comparison with free PPT. Therefore, PPT-Lips represent an efficient and promising drug delivery system for PPT.

Self-assembling ferrimagnetic fluorescent micelles for bioimaging guided efficient magnetic hyperthermia therapy.

Multifunctional magnet-fluorescent nanocomposites are widely applied in biomedical applications. Incorporating biocompatible quantum dots with highly ferrimagnetic magnetic nanoparticles into one nanoplatform for achieving efficient magnetic hyperthermia therapy (MHT) is very important. Herein, we reported an amphiphilic block copolymer with a flowable hydrophobic chain to encapsulate highly ferrimagnetic magnetic nanoparticles and ZnS/InP quantum dots via a facile self-assembly method. The obtained ferrimagnetic fluorescent micelle (FMFM) exhibited a uniform diameter of about 180 nm. In stark contrast, larger aggregation (400 nm in diameter) inevitably occurred using common poly(D,L-lactide) (PLA)-based amphiphilic block copolymer with a rigid hydrophobic chain, which was readily cleared by the reticuloendothelial system (RES). The flowable FMFM exhibited long-term colloidal stability within one month and desired fluorescent stability within 84 h. Benefiting from the high ferrimagnetism, the FMFM revealed excellent magnetic heating effect and magnetic resonance imaging capability. With accurate manipulation under an external magnetic field, FMFM realized in vitro enhanced fluorescence imaging sensitivity and accumulation efficiency at the tumor region, achieving in vitro and vivo improved MHT efficacy.

Thermoresponsive in Situ Forming Hydrogel with Sol-Gel Irreversibility for Effective Methicillin-Resistant Staphylococcus aureus Infected Wound Healing.

An in situ forming hydrogel has emerged as a promising wound dressing recently. As physically cross-linked hydrogels are normally unstable, most in situ forming hydrogels are chemically cross-linked. However, big concerns have remained regarding the slow gelation and the potential toxicity of residual functional groups from cross-linkers or the polymer matrix. Herein, we report a sprayable in situ forming hydrogel composed of poly(N-isopropylacrylamide166-co-n-butyl acrylate9)-poly(ethylene glycol)-poly(N-isopropylacrylamide166-co-n-butyl acrylate9) copolymer (P(NIPAM166-co-nBA9)-PEG-P(NIPAM166-co-nBA9), denoted as PEP) and silver-nanoparticles-decorated reduced graphene oxide nanosheets (Ag@rGO, denoted as AG) in response to skin temperature. This thermoresponsive hydrogel exhibits intriguing sol-gel irreversibility at low temperatures for the stable dressing of a wound, which is attributed to the inorganic/polymeric dual network and abundant coordination interactions between Ag@rGO nanosheets and PNIPAM. The biocompatibility and antibacterial ability against methicillin-resistant Staphylococcus aureus (MRSA) of this PEP-AG hydrogel wound dressing are confirmed in vitro and in vivo, which could transparently promote the healing of a MRSA-infected skin defect.

Magnetic liposomal emodin composite with enhanced killing efficiency against breast cancer.

As an active natural ingredient extracted from the plant Rheum palmatum, emodin exhibits various pharmacological activities, especially the inhibition of tumor growth and migration. However, the anticancer activity of emodin is limited mainly due to its poor solubility and the lack of specific targeting. Herein, we employed liposome to load emodin into the lipid bilayer, and high-performance ferromagnetic iron oxide nanocubes were simultaneously encapsulated in the hydrophilic bilayer. The optimized magnetic liposomal emodin nanocomposite (MLE) exhibited a 24.1% increase in the efficiency of killing MCF-7 cancer cells at a low concentration of 16 µg mL-1 compared with that of the hydrophobic free emodin. A further 8.67% enhancement of the killing efficiency was obtained by magnetic targeting. Benefitting from the high ferromagnetism, the transverse relaxivity (r2) of MLE was measured to be as high as 392.9 mM-1 s-1. With guidance from the external magnetic field, the effective accumulation of this magnetic liposome in the tumor region of a 4T1 breast tumor bearing mouse was observed by both MR tracking and fluorescence imaging, which should be beneficial for decreasing the required therapeutic dose of emodin. Hemolysis, cytotoxicity and biochemistry assays confirmed the excellent biocompatibility of this magnetic liposomal carrier. The anti-tumor therapeutic effect of MLE was further investigated in vivo, and the tumor in the therapeutic group was almost eliminated, indicating that this magnetic liposomal emodin could serve as a novel magnetically guided theranostic nanoagent.