Age-related macular degeneration (AMD) is a leading cause of blindness in the modern world. The standard treatment regimen for neovascular AMD is the monthly/bimonthly intravitreal injection of anti-VEGF agents such as ranibizumab or aflibercept. However, these repeated invasive injections can lead to sight-threatening complications. Sustained delivery by encapsulation of the drug in carriers is a way to reduce the frequency of these injections. Liposomes are biocompatible, non-toxic vesicular nanocarriers, which can be used to encapsulate therapeutic agents to provide sustained release. The protein encapsulation was performed by a modified dehydration-rehydration (DRV) method. The liposomes formed were characterized for size, zeta potential, encapsulation efficiency, stability, in vitro release, and ex vivo release profiles. In addition, the localization of the liposomes themselves was studied ex vivo. Entrapment-efficiency of ranibizumab into 100-nm liposomes varied from 14.7 to 57.0%. Negatively-charged liposomes prepared from DPPC-DPPG were found to have the slowest release with a low initial burst release compared to the rest of liposomal formulations. The ex vivo protein release was found to slower than the in vitro protein release for all samples. In conclusion, the DPPC-DPPG liposomes significantly improved the encapsulation and release profile of ranibizumab.
Currently, infections following cataract surgery are not as effectively managed with antibiotic eye drops, which suffer from poor bioavailability of drug and low patient compliance. The ideal solution, which can help to overcome the issue of drug wastage and poor bioavailabilty, as well as the need for frequent applications (patient inconvenience), is a drug-eluting intraocular lens (IOL). We describe a novel approach to such a drug-eluting lens by using a peripheral IOL attachment as a drug depot to deliver antibiotics, Levofloxacin (LFX) or Moxifloxacin (MFX). In this work, drug was entrapped within a fully-degradable polymer, poly(L-lactide-co-ɛ-caprolactone) (PLC). The effects of drug loading and solvent type on drug release and film morphology were investigated using cast films. The study clearly demonstrated that a slower-evaporating solvent tetrahydrofuran (THF) resulted in a better surface morphology, as well as lower initial burst compared to dichloromethane (DCM), and hence, was better suited to developing a drug-eluting attachment with sustained release of drug. When attachments were fabricated with drugs at high loading percentages (20% and 25% in polymer), significant burst was observed compared to films: this is attributed to the higher surface-to-volume ratio of the attachments. When the levofloxacin (LFX) loading percentage was decreased to 3% and 5%, the attachments presented lower burst and sustained release with therapeutic efficacy. This work has demonstrated the potential of using an IOL attachment as a more efficacious anti-infective option compared to daily eye drops.
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