Development of Cell-Penetrating Peptide-Modified Multifunctional Nanoparticles as Drug Carriers for the Treatment of Age-Related Macular Degeneration

Age-related macular degeneration (AMD) therapy is an attractive research topic in clinical ophthalmology. Current treatment modalities for AMD generally require long-term intravitreal injections of antiangiogenic agents. Nevertheless, unfavorable secondary effects of intraocular inflammation and retinal injury are usually seen in patients receiving multiple dosing regimens. Given that the pharmacological action of bevacizumab/ranibizumab is targeted at vascular endothelial growth factor (VEGF), these antiangiogenic agents may also cause abnormal retinal physiology such as tissue dystrophy and atrophy through directing binding with VEGF molecules. Furthermore, low ocular bioavailability attributed to cell/tissue barriers to mass transport remains to be a major issue for intravitreal drug administration. More importantly, it has been recognized that angiogenesis, inflammation, oxidative stress, and geographic atrophy play crucial roles in the pathogenesis of AMD and irreversible visual loss. To overcome these drawbacks, it is highly desirable to develop therapeutic drug carriers composed of functionalized biomaterials that simultaneously exhibit high antiinflammatory/antioxidative/antiangiogenic activities and delivery performances, thereby offering benefits to the treatment of posterior segment diseases such as macular degeneration. In this study, we hypothesize that the incorporation of cell-penetrating peptide (CPP), metformin, resveratrol, and lampalizumab into hollow poly(ε-caprolactone) (PCL) nanoparticles can significantly enhance drug loading and delivery as well as alleviate disease-related damges. To our knowledge, such a design has not yet been implemented, and therefore this is a new direction for further research in the development of ophthalmic biomaterials and dosage forms. This three-year project aims to investigate whether the use of CPP as tissue-penetration enhancer can boost the therapeutic efficacy of injectable multifunctional hollow PCL nanoparticles as drug carriers to prevent disease progression of AMD. In the first year, we will focus on the characterization and biocompatibility of synthesized hollow PCL nanocarriers functionalized with CPP, metformin, and resveratrol molecules. Further work over the next year will be optimization studies to evaluate the effects of CPP type and polymer chain length on numerous biological properties of drug carriers. In the final year of the study, we will pay particular attention to the examination of CPP-modified multifunctional nanoparticles for intraocular lampalizumab delivery platform that can rescue tissue damage caused by AMD. It is expected that the proposed therapeutic drug delivery system in this project will be beneficial in helping people who are experiencing vision loss.

Project ID:PC10901-0512
External Project ID:MOST107-2314-B182-016-MY3