# Steering the Clinical Translation of Delivery Systems for Drugs and Health Products
## 3 Poster Presentations
### In Vitro and in Vivo Evaluation of Dexamethasone Loaded Oligocation Liposomes in Retinal Diseases  
[PERSON] 1, [PERSON] 1, [PERSON] 2, [PERSON] 2, [PERSON] 2, [PERSON] 3, [PERSON] 2, [PERSON] 1, [PERSON] 1 and [PERSON] 1,*  
1 Department of Pharmaceutical and Pharmacological Sciences, University of Padua, [PERSON] 5, 35131 Padua, Italy  
2 Dentistry and Biomedical Sciences, Queen's University Belfast, School of Medicine, 97 Lisburn Road, Belfast, BT97 BL  
3 Division of Pharmaceutical Biosciences, University of Helsinki, Viikinkaari 5 E, 00014, 00100 Helsinki Finland  
* Correspondence: [EMAIL_ADDRESS]  
Retina is an integral part of the eye responsible for vision and various diseases are associated with retinal degeneration [15]. Unique anatomy of the eye poses challenges to efficient delivery of therapeutics to the retina [16]. Surface decorated liposomes represent a valid delivery strategy to improve residence time of drugs in the vitreous, thus reducing administration frequency, and effective interaction with retinal barrier to facilitate intracellular access [17]. In this study, we aimed at modulating the surface properties of liposomes with a combination of mPEG2 kDa-DSPE and a newly synthesized oligocationic non-peptide non-linear cell penetration enhancer (CPE) to control both their diffusivity in the vitreous and intracellular access. The nano platform has been used to deliver the anti-inflammatory agent dexamethasone by intravitreal administration. Dexamethasone loaded liposomes were prepared by remote loading approach using calcium acetate gradient. A variety of formulation parameters were investigated to assess their effect on the loading efficiency and capacity, and colloidal features. Dexamethasone loaded liposomes were decorated with 5 mol % CPE and 5 mol % mPEG2 kDa-DSPE. Cryo-EM analysis has been performed in various liposomal formulations. In vitro release and stability studies have been carried out in buffer at pH 7.4 and 37 \({}^{\circ}\)C. In vitro cyto-toxicity and anti-inflammatory activity of liposomes were tested in ARPE19 cell line. In vivo efficacy of the liposomes was evaluated by intra-vitreal injection of the formulations in a C57 BL/6 mouse model after laser induced choroidal neo-vascularization in retina. Dexamethasone hemisuccinate loaded liposomes were successfully fabricated with a size of ~170 nm and low PDI (<0.1). The CPE decorated liposomes showed a positive zeta potential (+13 mV), while CPE/PEG-coated liposomes displayed a slightly positive zeta potential of +3.7 mV because of PEG shielding of the CPE. Cryo-EM analysis demonstrated the presence of dexamethasone-calcium rod shape matrix in the aqueous phase of the liposomes similarly to Doxyl. In vitro release studies  
Figure 8: MIC of GM/NHs or LVF/NHs against planktonic (**A**) or intracellular (**B**) _S. aureus_ in HaCaT. demonstrated a slow release of dexamethasone for 20 days. Each formulation was colloidally stable over 20 days indicated by no significant changes in size and P.D.I. The liposomal formulation was not toxic to the retinal cells and dose dependent decrease of pro-inflammatory cytokine (IL-6) was observed in LPS induced cell model. Ongoing in vivo test will assess the effect in reducing the neovascularization process by looking at the eye fundus and quantifying the vascularization area with respect to controls. In conclusion, in this study dexamethasone loaded liposomes were generated and their in vitro biopharmaceutical profile has been investigated. The modulation of surface properties of liposomes by multifunctional components represents a relevant strategy to enhance their residence time in the vitreous and while promoting access to target cells for anti-inflammatory drug delivery. This surface decorated liposomal delivery system might be a promising approach to treat retinal diseases. This project has received funding from the European Union's Horizon 2020 research and innovation program under the [PERSON] grant agreement N\({}^{\circ}\) 722717. The authors declare no conflict of interest.