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Pharmacokinetic Simulations of Intravitreal Biologicals: Aspects of Drug Delivery to the Posterior and Anterior Segments
摘要： Biologicals are important ocular drugs that are be delivered using monthly and bimonthly intravitreal injections to treat retinal diseases, such as age-related macular degeneration. Long acting delivery systems are needed for prolongation of their dosing interval. Intravitreal biologicals are eliminated from the eye via the aqueous humor outflow. Thus, the anterior and posterior segments are exposed to the drug. We utilized a kinetic simulation model to estimate protein drug concentrations in the vitreous and aqueous humor after bolus injection and controlled release administration to the vitreous. The simulations predicted accurately the experimental levels of 5 biologicals in the vitreous and aqueous humor. The good match between the simulations and experimental data demonstrated almost complete anterior segment bioavailability, and major dose sparing with ocular controlled release systems. Overall, the model is a useful tool in the design of intraocular delivery of biologicals.
关键词： aflibercept,ocular drug delivery,ranibizumab,intravitreal injection,controlled release,bevacizumab
更新于2025-09-23 15:22:29
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Nepafenac-Loaded Cyclodextrin/Polymer Nanoaggregates: A New Approach to Eye Drop Formulation
摘要： The topical administration route is commonly used for targeting therapeutics to the eye; however, improving the bioavailability of drugs applied directly to the eye remains a challenge. Different strategies have been studied to address this challenge. One of them is the use of aggregates that are formed easily by self-assembly of cyclodextrin (CD)/drug complexes in aqueous solution. The aim of this study was to design a new eye drop formulation based on aggregates formed between CD/drug complexes. For this purpose, the physicochemical properties of the aggregates associated with six CDs and selected water-soluble polymers were analysed. Complex formation was studied using differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR) and 1H nuclear magnetic resonance spectroscopy (1H-NMR). Results showed that HPβCD performed best in terms of solubilization, while γCD performed best in terms of enhancing nanoaggregate formation. Formation of inclusion complexes was con?rmed by DSC, FT-IR and 1H-NMR studies. A mixture of 15% (w/v) γCD and 8% (w/v) HPβCD was selected for formulation studies. It was concluded that formulations with aggregate sizes less than 1 μm and viscosity around 10–19 centipoises can be easily prepared using a mixture of CDs. Formulations containing polymeric drug/CD nanoaggregates represent an interesting strategy for enhanced topical delivery of nepafenac.
关键词： cyclodextrin,self-assemble,nepafenac,aggregate,polymer,complexation,ocular drug delivery
更新于2025-09-23 15:22:29
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Silk fibroin nanoparticles for enhanced bio-macromolecule delivery to the retina
摘要： The aim of this study was to investigate intravitreal injection of silk fibroin nanoparticles (SFNs) encapsulating bio-macromolecules, achieving enhanced drug bioavailability and extended retention in retina. SFNs were prepared with regenerated silk fibroin (RSF) using desolvation method with fluorescein isothiocyanate labeled bovine serum albumin (FITC-BSA) as bio-macromolecular model drug encapsulated. In vitro physicochemical properties and in vitro drug release of FITC-BSA loaded SFNs (FITC-BSA-SFNs) were evaluated. Cytotoxicity, cellular uptake, and retention of FITC-BSA-SFNs were determined in human retinal pigment epithelial cell line (ARPE-19). In addition, in vivo distribution and safety of intravitreally administered FITC-BSA-SFNs were investigated in New Zealand white rabbits. The particle size of FITC-BSA-SFNs was 179.1±3.7 nm with polydispersity index (PDI) of 0.102±0.033 and the zeta potential was greater than -25 mV. FITC-BSA-SFNs exhibited excellent biocompatibility with no cytotoxicity observed within 24 h and 48 h in AREP-19 cells. Compared to FITC-BSA solution, FITC-BSA-SFNs showed enhanced cellular uptake and prolonged retention. Furthermore, FITC-BSA-SFNs achieved accumulated distribution and extended retention in retina in vivo following intravitreal injection compared to a single administration of free drug solution. Therefore, this bio-macromolecule delivery platform based on SFNs could have great potential in the treatment of posterior segment disorders.
关键词： bio-macromolecules,Silk fibroin nanoparticles,ocular drug delivery,posterior segment diseases,intravitreal injection
更新于2025-09-10 09:29:36