Design and synthesis of lipidic organoalkoxysilanes for the self-assembly of liposomal nanohybrid cerasomes with controlled drug release properties.

This paper reports the facile design and synthesis of a series of lipidic organoalkoxysilanes with different numbers of triethoxysilane headgroups and hydrophobic alkyl chains linked by glycerol and pentaerythritol for the construction of cerasomes with regulated surface siloxane density and controlled release behavior. It was found that the number of triethoxysilane headgroups affected the properties of the cerasomes for encapsulation efficiency, drug loading capacity, and release behavior. For both water-soluble doxorubicin (DOX) and water-insoluble paclitaxel (PTX), the release rate from the cerasomes decreased as the number of triethoxysilane headgroups increased. The slower release rate from the cerasomes was attributed to the higher density of the siloxane network on the surface of the cerasomes, which blocks the drug release channels. In contrast to the release results with DOX, the introduction of one more hydrophobic alkyl chain into the cerasome-forming lipid resulted in a slower release rate of PTX from the cerasomes due to the formation of a more compact cerasome bilayer. An MTT viability assay showed that all of these drug-loaded cerasomes inhibited proliferation of the HepG2 cancer cell line. The fine tuning of the chemical structure of the cerasome-forming lipids would foster a new strategy to precisely regulate the release rate of drugs from cerasomes.

In vitro and in vivo evaluation of a photosensitive polyimide thin-film microelectrode array suitable for epiretinal stimulation.

BACKGROUND: Epiretinal implants based on microelectro-mechanical system (MEMS) technology with a polyimide (PI) material are being proposed for application. Many kinds of non-photosensitive PIs have good biocompatibility and stability as typical MEMS materials for implantable electrodes. However, the effects of MEMS microfabrication, sterilization and implantation using a photosensitive polyimide (PSPI) microelectrode array for epiretinal electrical stimulation has not been extensively examined. METHODS: A novel PSPI (Durimide 7510) microelectrode array for epiretinal electrical stimulation was designed, fabricated based on MEMS processing and microfabrication techniques. The biocompatibility of our new microelectrode was tested in vitro using an MTT assay and direct contact tests between the microelectrode surface and cells. Electrochemical impedance characteristics were tested based on a three-electrode testing method. The reliability and stability was evaluated by a chronic implantation of a non-functional array within the rabbit eye. Histological examination and SEM were performed to monitor possible damage of the retina and microelectrodes. Electrically evoked potentials (EEPs) were recorded during the acute stimulation of the retina. RESULTS: The substrate was made of PSPI and the electrode material was platinum (Pt). The PSPI microelectrode array showed good biocompatibility and appropriate impedance characteristics for epiretinal stimulation. After a 6-month epiretinal implantation in the eyes of rabbits, we found no local retinal toxicity and no mechanical compression caused by the array. The Pt electrodes adhesion to the PSPI remained stable. A response to electrical stimuli was with recording electrodes lying on the visual cortex. CONCLUSION: We provide a relevant design and fundamental characteristics of a PSPI microelectrode array. Strong evidences on testing indicate that implantation is safe in terms of mechanical pressure and biocompatibility of PSPI microelectrode arrays on the retina. The dual-layer process we used proffers considerable advantages over the more traditional single-layer approach and can accommodate much many electrode sites. This lays the groundwork for a future, high-resolution retinal prosthesis with many more electrode sites based on the flexible PSPI thin film substrate.

Film from peroxidation of an amino phospholipid and its biocompatibility.

A new kind of phospholipid product with fluorescence was derived from autoxidation of an aminophospholipid, L-alpha-phosphatidylethanolamine dilinoleoyl in solid film state. Atomic force microscopy showed that the film product was composed of round and elliptical vesicles with diameters of about 20-45 nm. The product was difficult to dissolve in water and most organic solvents. Fourier transform infrared spectroscopy, solid-state (13)C NMR, and solid-state (31)P NMR indicated that the unsaturated double carbon bond decreased with the reaction, and polymerization within/between phospholipid molecules occurred. Endothelial cells from human vein seeded onto the film showed the highest proliferating activity compared with seeding onto Corning culture plate, glass plate, or phospholipid film with phosphorylcholine head group, as evaluated by 3-(4,5-timethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay (p < 0.001). The hemocompatibility of the film was also assessed by platelet adhesion and protein adsorption. The results suggest that the product has potential applications as a new biomaterial coating.

Overcoming foreign-body reaction through nanotopography: Biocompatibility and immunoisolation properties of a nanofibrous membrane.

Implantable immunoisolation membranes need to possess superior biocompatibility to prohibit the fibrotic deposition that would reduce the nutrient supply and impair the viability/function of the encapsulated cells. Here, electrospun membranes based on thermoplastic polyurethane (TPU) were fabricated to contain microfibers (PU-micro) or nanofibers (PU-nano). The two types of membranes were compared in terms of their interaction with macrophage cells and the host tissues. It was found that the fibrous membranes of different topographies possess distinct material properties: PU-nano caused minimal macrophage responses in vitro and in vivo and induced only mild foreign body reactions compared to PU-micro membranes. A flat macroencapsulation device was fabricated using PU-nano membranes and its immunoisolation function investigated in subcutaneous transplantation models. The nanofibrous device demonstrated the capability to effectively shield the allografts from the immune attack of the host. Nanotopography may confer biocompatibility to materials and nanofibrous materials warrant further study for development of "invisible" immunoisolation devices for cell transplantation.

Viscous optical clearing agent for in vivo optical imaging.

By allowing more photons to reach deeper tissue, the optical clearing agent (OCA) has gained increasing attention in various optical imaging modalities. However, commonly used OCAs have high fluidity, limiting their applications in in vivo studies with oblique, uneven, or moving surfaces. In this work, we reported an OCA with high viscosity. We measured the properties of this viscous OCA, and tested its successful performances in the imaging of a living animal's skin with two optical imaging modalities: photoacoustic microscopy and optical coherence tomography. Our results demonstrated that the viscous OCA has a great potential in the study of different turbid tissues using various optical imaging modalities.

Uniform polypyrrole nanoparticles with high photothermal conversion efficiency for photothermal ablation of cancer cells.

Uniform polypyrrole (PPy) nanoparticles are fabricated from a facile one-step aqueous dispersion polymerization. Owing to their high photothermal conversion efficiency and photostability compared with the well-known Au nanorods, as well as their good colloidal stability and biocompatibility, the resulting PPy nanoparticles can used as a novel promising photothermal ablation coupling agent for targeted treatment of cancer.

In vitro biocompatibility of a platinum-electrode embedded photosensitive polyimide (Durimide) retinal prosthesis.

PURPOSE: The photosensitive polyimide film, Durimide, is a common component of retinal prostheses; however, retinal cell response to Durimide has not been effectively studied This work assessed the in vitro biocompatibility of a retinal prosthesis containing platinum-electrode embedded Durimide film. MATERIALS AND METHODS: Biocompatibility evaluation assessed cytotoxicity, attachment, and proliferation of two cell lines: a human retinal pigmented epithelium cell line (CRL) and a rhesus monkey choroid- retinal endothelial cell line (RF/6A). Cells were cultured with the platinum-electrode embedded Durimide film, with tissue-culture treated polystyrene plates (TCPS) used as a control substrate for cell growth. The effect of a Durimide-exposed medium on cell apoptosis and life cycle was assessed using flow cytometry (FCM). RESULTS: The indirect cytotoxicity evaluation revealed no toxic effect of the prosthesis on cells. The attachment and proliferation of CRL and RF/6A cells cultured with the Durimide prostheses showed no significant differences to the control. The FCM experiments demonstrated a liquid medium exposed to the prosthesis had no effects on apoptosis or cell life cycle in comparison with the control (p > 0.05). CONCLUSIONS: The results demonstrate that Durimide has good biocompatibility with retinal cell lines CRL and RF/6A. In conclusion, while further in vitro and in vivo studies are required to clarify long-term effects, Durimide is indicated as a promising material with suitable biocompatibility for retinal implants.

Efficacy of intravenous amphotericin B-polybutylcyanoacrylate nanoparticles against cryptococcal meningitis in mice.

Amphotericin B deoxycholate (AmB), a classic antifungal drug, remains the initial treatment of choice for deep fungal infections, but it is not appropriate for treatment of cryptococcal meningitis due to its inability to pass through the blood-brain barrier (BBB). We examined the efficacy of amphotericin B-polybutylcyanoacrylate nanoparticles (AmB-PBCA-NPs) modified with polysorbate 80 that had a mean particle diameter less than 100 nanometers (69.0 ± 28.6 nm). AmB-PBCA-NPs were detected in the brain 30 minutes after systemic administration into BALB/c mice and had a higher concentration than systemically administered AmB liposome (AmB-L, P < 0.05); AmB was not detected in the brain. Following infection for 24 hours and then 7 days of treatment, the survival rate of mice in the AmB-PBCA-NP group (80%) was significantly higher than that of the AmB (0%) or AmB-L (60%) treatment groups. Fungal load was also lower when assessed by colony-forming unit counts obtained after plating infected brain tissue (P < 0.05). Our study indicates that AmB-PBCA-NPs with polysorbate 80 coating have the capacity to transport AmB across the BBB and is an efficient treatment against cryptococcal meningitis in a mouse model.

Photo-sensitive liposomes: chemistry and application in drug delivery.

Photo-sensitive liposomes have been studied for a few decades and various photo-sensitive triggers have been developed so far. This review offers an overview of the different photo-triggering mechanisms for controlled pulsatile content release from liposomes, which have the potential of finding clinical applications as intelligent drug delivery systems.