A Nanogel Formulation of Anti-VEGF Peptide for Ocular Neovascularization Treatment.

Age-related macular degeneration (AMD) is an eye disorder that can lead to visual impairment in elder patients, and current treatments include repeated injections of monoclonal antibody-based antivascular endothelial growth factor (anti-VEGF) agents. This study investigates the potential of a nanoformulation of a peptide anti-VEGF molecule for neovascular AMD. Anti-VEGF peptide HRHTKQRHTALH (HRH), which has high affinity to VEGF-Fc receptor, was used as the bioactive agent to control neovascularization of the retina. The nanoformulation consisting of hyaluronic acid nanogel was generated by incorporating divinyl sulfone and cholesterol to increase the stability and control the size of the nanodrug. The encapsulation efficacy of nanogel was 65%, and drug release was 34.72% at the end of 192 h. Obtained nanogels were efficiently internalized in 15 min by human umbilical vascular endothelial cells (HUVECs) and ARPE-19 cells, and results indicate that nanoformulation is not toxic to ARPE-19 cells, whereas it inhibits HUVEC proliferation owing to anti-VEGF peptide in the nanogel structure. In the coculture experiment in which retinal penetration was modeled, it was observed that the nanogel reached HUVECs and negatively affected their proliferation without disturbing the monolayer of ARPE-19 cells. In vivo experiments with chick chorioallantoic membrane revealed that nanogel formulation has higher antiangiogenesis activity compared to free HRH. Additionally, in an oxygen-induced retinopathy model, the excessive growth of blood vessels was notably suppressed in mice treated with HRH-loaded nanogel. This research indicates that nanogels formulated in this study are promising candidates as a topical treatment for AMD.

A Flexible Cystoscope Based on Hydrodynamic Cavitation for Tumor Tissue Ablation.

OBJECTIVE: Hydrodynamic cavitation is characterized by the formation of bubbles inside a flow due to local reduction of pressure below the saturation vapor pressure. The resulting growth and violent collapse of bubbles lead to a huge amount of released energy. This energy can be implemented in different fields such as heat transfer enhancement, wastewater treatment and chemical reactions. In this study, a cystoscope based on small scale hydrodynamic cavitation was designed and fabricated to exploit the destructive energy of cavitation bubbles for treatment of tumor tissues. The developed device is equipped with a control system, which regulates the movement of the cystoscope in different directions. According to our experiments, the fabricated cystoscope was able to locate the target and expose cavitating flow to the target continuously and accurately. The designed cavitation probe embedded into the cystoscope caused a significant damage to prostate cancer and bladder cancer tissues within less than 15 minutes. The results of our experiments showed that the cavitation probe could be easily coupled with endoscopic devices because of its small diameter. We successfully integrated a biomedical camera, a suction tube, tendon cables, and the cavitation probe into a 6.7 mm diameter cystoscope, which could be controlled smoothly and accurately via a control system. The developed device is considered as a mechanical ablation therapy, can be a solid alternative for minimally invasive tissue ablation methods such as radiofrequency (RF) and laser ablation, and could have lower side effects compared to ultrasound therapy and cryoablation.

Niosomal Drug Delivery Systems for Ocular Disease-Recent Advances and Future Prospects.

The eye is a complex organ consisting of several protective barriers and particular defense mechanisms. Since this organ is exposed to various infections, genetic disorders, and visual impairments it is essential to provide necessary drugs through the appropriate delivery routes and vehicles. The topical route of administration, as the most commonly used approach, maybe inefficient due to low drug bioavailability. New generation safe, effective, and targeted drug delivery systems based on nanocarriers have the capability to circumvent limitations associated with the complex anatomy of the eye. Nanotechnology, through various nanoparticles like niosomes, liposomes, micelles, dendrimers, and different polymeric vesicles play an active role in ophthalmology and ocular drug delivery systems. Niosomes, which are nano-vesicles composed of non-ionic surfactants, are emerging nanocarriers in drug delivery applications due to their solution/storage stability and cost-effectiveness. Additionally, they are biocompatible, biodegradable, flexible in structure, and suitable for loading both hydrophobic and hydrophilic drugs. These characteristics make niosomes promising nanocarriers in the treatment of ocular diseases. Hereby, we review niosome based drug delivery approaches in ophthalmology starting with different preparation methods of niosomes, drug loading/release mechanisms, characterization techniques of niosome nanocarriers and eventually successful applications in the treatment of ocular disorders.