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Development of co‐encapsulating bevacizumab and dexamethasone liposomes with cell penetrating peptide surface functionalisation for posterior eye drug delivery

脂质体 地塞米松 药理学 贝伐单抗 药物输送 医学 色谱法 小泡 化学 生物医学工程 材料科学 纳米技术 化疗 外科 生物化学 内科学
作者
Umer Farooq,Laurence Fitzhenry,Niall J. O’Reilly,Gautam Behl,Zubair Ahmed,Paolo Gasco,Thakur Raghu Raj Singh,Peter McLoughlin
出处
期刊:Acta Ophthalmologica [Wiley]
卷期号:100 (S275)
标识
DOI:10.1111/j.1755-3768.2022.15541
摘要

Abstract Background: Intravitreal injections to the eye are the standard treatment for wet age‐related macular degeneration (AMD) but are associated with several drawbacks. Intravitreal injections not only cause structural damage but the invasive procedure also causes discomfort and pain, resulting in decreased patient adherence to the therapy. Our work aims to develop a topical liposomal formulation, functionalised with a cell penetrating peptide (CPP) that has the potential to reach the posterior segment of the eye and inhibit neovascularisation and inflammation, which are the hallmarks of wet AMD and Diabetic Retinopathy. The proposed formulation will offer non‐invasive administration (topical) with decreased dosing frequency (owing to its sustained release action), facilitating increased patient compliance. Methods: The liposomes were prepared by the thin film hydration method, followed by the extrusion of obtained multilamellar vesicles into single unilamellar vesicles. The formulations were characterized for their size, PDI and % encapsulation efficiency (%EE). Initially, a Design of Experiments approach was adopted to optimize the encapsulation efficiency of dexamethasone in liposomes, with the amounts of DPPC, cholesterol and dexamethasone being the factors and the size, PDI and %EE as the responses. HPLC was used to quantify the amount of encapsulated dexamethasone. Bevacizumab was then co‐loaded with optimized dexamethasone liposome formulation and bicinchoninic acid (BCA) assay was used to quantify the amount of encapsulated bevacizumab in the liposomes. Results: Liposomes with an average size of 137 ± 3 nm, PDI of 0.07 ± 0.03 and a zeta potential of −3.09 ± 0.42 were synthesized. Dexamethasone encapsulation efficiency was improved from initially observed value of 13.01 ± 0.06 to the optimized value of 52.8 ± 2.5. This optimized formulation has a %EE 5.8 time greater than the previously reported values for DPPC‐dexamethasone liposomes (1). Bevacizumab was successfully co‐encapsulated into the liposomes along with dexamethasone. Bevacizumab demonstrated %EE of 91.3 ± 4.07 in the dual encapsulated liposomes, whereas %EE of dexamethasone was 75.1 ± 4.4. Further studies: The liposome formulation will be functionalised with the CPP and characterized for drug release, transport through ocular layers, cytotoxicity, anti‐angiogenesis and anti‐inflammatory activities using in vitro, ex vivo and in vivo models. References 1. Bhardwaj U, Burgess DJ. Physicochemical properties of extruded and non‐extruded liposomes containing the hydrophobic drug dexamethasone. Int J Pharm. 2010;388(1–2):181–9. This project is funded by the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska‐Curie Actions (grant agreement – No 813440).

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