Ocular Therapeutics and Molecular Delivery Strategies for Neovascular Age-Related Macular Degeneration (nAMD)

Abstract

Age-related macular degeneration (AMD) is the leading cause of vision loss in geriatric population. Intravitreal (IVT) injections are popular clinical option. Biologics and small molecules offer efficacy but relatively shorter half-life after intravitreal injections. To address these challenges, numerous technologies and therapies are under development. Most of these strategies aim to reduce the frequency of injections, thereby increasing patient compliance and reducing patient-associated burden. Unlike IVT frequent injections, molecular therapies such as cell therapy and gene therapy offer restoration ability hence gained a lot of traction. The recent approval of ocular gene therapy for inherited disease offers new hope in this direction. However, until such breakthrough therapies are available to the majority of patients, antibody therapeutics will be on the shelf, continuing to provide therapeutic benefits. The present review aims to highlight the status of pre-clinical and clinical studies of neovascular AMD treatment modalities including Anti-VEGF therapy, upcoming bispecific antibodies, small molecules, port delivery systems, photodynamic therapy, radiation therapy, gene therapy, cell therapy, and combination therapies.

Bionanofactories for Green Synthesis of Silver Nanoparticles: Toward Antimicrobial Applications

“…This vast range of phytochemicals includes Aloe vera plant extract [ 20 ], Mangifera indica fruit extract [ 21 ], Murraya koenigii leaf [ 22 ], and others carbohydrates [ 23 ]. Glucose was also utilized to synthesize AgNPs along with the appearance of stabilizing agents such as soluble starch [ 5 , 24 , 25 ], sucrose, and maltose [ 26 ]. One of the very well-known plants is Eucalyptus [ 27 ], whereas Bacillus methylotrophicus [ 28 ] has also attracted interest in green synthesis.…”

“…The resultant nanoparticles were found to be stable and similar in properties (e.g., polydispersity and shape) to AgNPs obtained using conventional techniques of synthesis [ 148 ]. AgNP [ 24 ] synthesis utilizes water (solvent) and polysaccharides (capping agent) such as starch and heparin in this process. This method is reported to be advantageous as the binding interactions between AgNPs and starch are quite weak and are noted to reverse at higher temperatures, thus assisting the segregation of the obtained NPs.…”

“…Uniform AgNPs were also fabricated by microwave radiation [ 1 , 24 ] of a carboxymethyl cellulose sodium (CMS) and silver nitrate solution. The NPs generated were uniform and appreciably stable at room temperature for around 2 months [ 172 ].…”

“…AgNPs [ 103 ] have displayed significant antimicrobial activity alone and in combination with antibiotics, mediated by three possible mechanisms: (i) cell wall and membrane damage, (ii) intracellular penetration and damage, and (iii) oxidative stress [ 83 , 103 , 210 ]. In one study [ 24 ], it was shown that AgNPs formed using disaccharides such as maltose and lactose possessed greater activity compared to those synthesized using monosaccharides such as glucose and galactose. This could be due to the smaller size of disaccharides compared to monosaccharides.…”

“…The antibacterial effects of these nanoparticles may also correspond to [ 82 ] a dual mechanism that includes the bactericidal effect of Ag + ions and the membrane-disrupting effect of the polymer subunits. Moreover, in other applications [ 24 ], silver aerosol NPs were found to be significantly active as antimicrobials toward B. subtilis [ 211 ]. They have also been utilized in antimicrobial water filters, in activated carbon fiber (ACF) filters [ 212 ], and for the removal of bioaerosols.…”