Background
Angiogenic ocular diseases address the main source of vision impairment or irreversible vision loss. The angiogenesis process depends on the balance between the pro-angiogenic and anti-angiogenic factors. An imbalance between these factors leads to pathological conditions in the body. The vascular endothelial growth factor is the main cause of pathological conditions in the ocular region. Intravitreal injections of anti-angiogenic drugs are selective, safe, specific and revolutionized treatment for ocular angiogenesis. But intravitreal injections are invasive techniques with other severe complications. The area of targeting vascular endothelial growth factor receptors progresses with novel approaches and therapeutically based hope for best clinical outcomes for patients through the developments in anti-angiogenic therapy.
Main text
The present review article gathers prior knowledge about the vascular endothelial growth factor and associated receptors with other angiogenic and anti-angiogenic factors involved in ocular angiogenesis. A focus on the brief mechanism of vascular endothelial growth factor inhibitors in the treatment of ocular angiogenesis is elaborated. The review also covers various recent novel approaches available for ocular drug delivery by comprising a substantial amount of research works. Besides this, we have also discussed in detail the adoption of nanotechnology-based drug delivery systems in ocular angiogenesis by comprising literature having recent advancements. The clinical applications of nanotechnology in terms of ocular drug delivery, risk analysis and future perspectives relating to the treatment approaches for ocular angiogenesis have also been presented.
Conclusion
The novel ocular drug delivery systems involving nanotechnologies are of great importance in the ophthalmological sector to overcome traditional treatments with many drawbacks. This article gives a detailed insight into the various approaches that are currently available to be a road map for future research in the field of ocular angiogenesis disease management.
Conjunctivitis is an inflammation of the conjunctiva, which covers the white part of the eyeball. It can be caused by allergies, bacterial or viral infection. In situ hydrogels are three-dimensional hydrophilic cross-linked network of polymers. In situ hydrogel provided better therapeutic index when compared to conventional treatment. The present work describes the formulation and evaluation of ofloxacin and dexamethasone based on the concept of pH triggered in situ gelation. Carbopol 934p was used as the gelling agent in combination with HPMC, as a viscosityenhancing agent, benzalkonium chloride as preservative, sodium chloride as tonicity adjusting agent. The prepared formulations were liquid at the low pH and underwent rapid transition into viscous gel at the pH of the tear fluid. Formulations were evaluated for various rheological, in vitro and in vivo release characteristics. Infrared spectroscopy studies showed that there were no interactions between the drug and polymers. Viscosity of the prepared hydrogels lies in the optimum range and drug was released up to 85 % as the end of 13 h. The prepared in situ hydrogel was sterile, non-irritant to the eye. The present study indicated that it is possible to develop safe and physiologically effective in situ hydrogel which is patient compliant.
Objective: The present investigation aims to develop nano in situ gels of bevacizumab and evaluate their safety and efficacy.
Methods: Nanoparticles were designed using the desolvation and double emulsion solvent evaporation technique. The hen’s egg test: chorioallantoic membrane (HET-CAM) assay was adopted to evaluate the anti-angiogenesis and irritancy potential of prepared nano in situ gel. Computational docking study carried out using glide module of Schrodinger software.
Results: The FT-IR study showed no interaction between the components. The drug-loaded nanoparticle showed particle size in the range of 369±5.3 to 410±3.5, followed by PDI 0.41±0.1 to 0.73±0.1, and ζ–Potential-13±2.3 to-9±3.4. The entrapment efficiency of nanoparticles was found in between the range of 72.35±1.4 to 87.22±1.1, followed by loading efficiency of 8.81±0.3 to 12.78±0.7. The FE-SEM studies resulted in an irregular pattern of aggregated particles. The spherical shape of the particles was confirmed through the HR-TEM study. The nano in situ gel exhibited pH in the range of 7.2±0.2 to 7.3±0.1 followed by a viscosity of 325.2±8.7 to 498.7±5.8 mPa. s. CAM assays revealed the safety and anti-angiogenesis activity of the developed formulation. All different concentrations of in situ gels of bevacizumab showed a significant anti-angiogenic effect. The outcome of the molecular docking study revealed the well-binding capacity of bevacizumab with vascular endothelial growth factor (-7.325) and human serum albumin (-5.620) residues.
Conclusion: The above outcomes improved our perception regarding the anti-angiogenic activity and safety of nano-in situ gels of bevacizumab. Overall, these findings denoted that implementing the current idea in the therapy of ocular angiogenesis might be a promising platform for better treatment.
Objective: The study aims to find a suitable method of developing silk fibroin-based anastrozole nanoparticles and formulate in situ injectables by loading the optimized nanoparticle formulation for the sustained release treatment of breast cancer.
Methods: The nanoparticles were formulated utilizing two different methods, solvent change and precipitation approach using silk fibroin. Prepared nanoparticles characterized in terms of size, zeta potential, polydispersity, and entrapment efficiency. The chosen optimized formulation (SF-ANS-NPs-1) was subsequently analyzed for compatibility investigations by Fourier-transform infrared spectroscopy (FT-IR), thermal analysis, surface morphology, x-ray diffraction, transmission electron spectroscopy, cumulative drug release, and stability studies as per ICH guidelines. Followed by formulating and evaluating in situ injectable gel using pluronic F-127.
Results: A particle size of 181.70±1.3 nm was reported by the optimized SF-ANS-NPs-1 formulation. FT-IR and thermal studies confirmed the compatibility of the drug with the polymers, and x-ray diffraction studies indicated crystalline nature. Surface morphology analysis indicated nano-size particle formation. A cumulative drug release (%CDR) of 94.15% was noted at the 168th hour. The results of the stability studies were indicated to be consistent over 90 d. In situ gel formulation showed desired spreadability, sol-gel transition temperature (37±0.5 ℃), viscosity (9.37±1.2 mPa·s), desired acidic pH, and a sustained release for 21 d (98.11%) with three months accelerated stability.
Conclusion: The results suggested that the combination of anastrozole with silk fibroin in the form of nanoparticles and in situ gelling systems could be an undoubtedly effective delivery method for prolonging breast cancer therapy.
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