Injectable nanoparticle suspension for vision recovery

Abstract

The disclosure refers to a composition comprising poly(3-hexylthiophene) nanoparticles suspended in a saline solution comprising a stabilizing agent selected from a non-ionic surfactant, a water-soluble polymer having high intrinsic viscosity and a combination thereof. The preferred water-soluble polymer is hyaluronic acid. The saline solution is an aqueous solution comprising at least sodium ions and chloride ions. The saline solution may further comprise at least one of: magnesium ions, calcium ions, potassium ions, and combination thereof. The formulation has demonstrated an improved effectiveness in restoring a visual response in the RCS rat model of blindness and is potentially effective in the treatment of human retinal dystrophies such as retinitis pigmentosa (RP) and macular degeneration (AMD).

Description

[0001] Injectable nanoparticle suspension for vision recovery

[0002] DESCRIPTION

[0003] Field of the disclosure

[0004] The present disclosure refers to nanoparticle compositions and their use for the treatment of visual impairment caused by progressive degeneration of eye photoreceptors, such as in the case of retinitis pigmentosa or macular degeneration.

[0005] Background art

[0006] In the developed and ageing world, progressive degeneration of the photoreceptors is becoming a serious cause of severe visual impairment and blindness. This phenomenon is a common evolution for two groups of ocular disorders: (A) retinal dystrophies, a group of genetic disorders typical of the young-adult age, which include Retinitis Pigmentosa, Leber Congenital Amaurosis (LCA), Achromatopsia, Cone Rod Dystrophy, and others,1and (B) retinal neurodegenerative diseases, a more common group of disorders, typical of adult-elder age, defined by different degrees of degeneration of both photoreceptors and retinal neurons (e.g., ganglion, bipolar, amacrine cells), which include age-related macular degeneration, diabetic retinopathy and glaucoma.2

[0007] The most common of the retinal dystrophies is retinitis pigmentosa (RP), a rare genetic disease affecting one person in 5,000 .3-5RP is characterized by a selective photoreceptor degeneration progressing from peripheral to the central retinal and leading almost invariably to legal blindness. RP accounts for approximately 250,000 cases in Europe, the United States of America and Japan, 30,000 of whom are legally defined as blind.

[0008] The most common retinal neurodegenerative disease affecting the photoreceptors is age-related macular degeneration (AMD). This disease has a multifactorial etiology and is more prevalent in older people, where the prevalence can be as high as 1 in 5.46AMD manifests in two distinct forms, wet-AMD, associated with retinal vessels overgrowth, and dry- AMD, the latter more rapidly evolving towards blindness.

[0009] It is estimated that there are 200,000,000 cases of AMD worldwide, of whom at least 20,000,000 are at risk of severe visual impairment and blindness.6

[0010] There are currently no definitive solutions for the legal or total blindness caused by these diseases: once their progression has led to extensive retinal atrophy and severe vision loss, no treatment can restore sight.

[0011] Several attempts have been made to slow down or even stabilize the loss of photoreceptors. For example, Luxturna®, a viral-mediated gene transfer, has been used successfully in a small number of patients to correct genetic defects in the RPE65 protein and prevent photoreceptor loss. The problem with this solution is that it is limited to one specific genetic defect, whereas there are more than 270 genes whose mutation leads to retinal dystrophies. In addition, this strategy is only effective in the early stages of the disease and cannot restore the function of dead photoreceptors.7-12

[0012] Another strategy to slow the progression of photoreceptor degeneration in wet AMD is based on the use of intraocular anti-VEGF treatments, which require repeated injections of specific drugs into the eye to reduce neovascularisation and prevent excessive degradation of photoreceptors. This treatment can delay the progression to legal blindness by several years, but again cannot restore what was lost at the time the treatment was started.13-21

[0013] In the last 10 years, some attempts to improve vision in blind patients affected by AMD or RP have been based on retinal implants of microelectrode arrays whose activation pattern was controlled by an external camera mounted on a pair of glasses. The retinotopic increase in currents in the respective visual field was shown to cause activation of retinal bipolar and ganglion neurons, acting as a prosthesis for degenerated photoreceptors. Such devices are an interesting solution, providing some coarse visual input, but they are expensive, cumbersome and may require periodic re-implantation, making them impractical and not justifying their use in large numbers of patients.22-27

[0014] There are other strategies to approach blindness in AMD and RP, including stem cell therapies, optogenetics, photobiomodulation, and DNA interference, but currently none of them has reached the market, nor has a clear preferred approach emerged.28-31

[0015] In the last decade, starting with the work of Lanzani et al. ,32organic semiconductors have attracted increasing interest as materials for retinal prostheses.

[0016] In particular, many works have suggested that poly(3-hexyltiophene) (P3HT) is biocompatible and able to elicit a response in neurons when illuminated with visible light.33-37

[0017] In 2017, a planar device composed of P3HT as a photoactive material organized in polymer layers fixed on a silk substrate was shown to restore vision in a blind rat model of RP up to 10 months after implantation without serious side effects.38The restoration has been proven by measuring the behavioral patterns of the animals and the Visual Evoked Potential (VEP) recorded in the visual cortex of the animals which is a parameter possessing a renowned connection with the ability to see.

[0018] In 2020, Maya-Vetencourt et al. showed a novel device consisting of P3HT nanoparticles (NP) dispersed in water that was able to restore vision in blind rats carrying a genetic mutation similar to RP (Royal College of Surgeon - RCS rats) once injected subretinally.39The effect of the particles lasted up to 9 months. Similar effects were observed when the NP’s subretinal injection was performed in older blind rats, suggesting some level of age-independent vision restoration.27The paper showed the use of NPs with a diameter of about 300 nm at a concentration of about 1 mg / ml. The particles remain extracellular and confer light sensitivity to inner retinal neurons. P3HT NPs were widely and persistently distributed throughout the subretinal space showing no sign of trophic effects on the remaining photoreceptors or evidence of local inflammatory response.

[0019] Although the studies showed highly significant effects of this innovative treatment in blind rats, there is no consensus on the mechanism how light sensitivity is restored and the question of how P3HT particles work is still hotly debated.40-42Indeed, the authors who tested the P3HT particles assumed that some form of charge generation creates currents or electrostatic potentials that can stimulate neurons. However, Palanker et al.42suggest that, given the light intensity and what is known from their extensive experience with inorganic retinal prostheses, the amount of current or charge generated should not be sufficient to produce the observed results in the blind rats.

[0020] This lack of consensus is reflected in the uncertainty about how nanoparticles can be modified or engineered to maintain their efficacy. In fact, as the mechanism is still being debated, it is not possible for anyone, even experts in the field, to say with certainty which modifications can alter the functionality of the particles and which modifications do not interfere with the effect of the particles. Therefore, changes in NP size, composition, concentration and / or supernatant may produce non-obvious results.

[0021] The nanoparticles used by Vetencourt et al. worked as a method to restore vision in blind animals,39but their translation to humans still poses several difficulties.

[0022] First, the proposed particles are dispersed in sterile water with a very low osmolality (about 5 mOsm / l), resulting in a very hypotonic solution. It is common knowledge that the use of a very hypotonic solution for intratissue or subretinal injection can induce osmotic stress and damage to the injected tissue cells exposed to a sudden change of extracellular fluid composition. This effect was not studied by the authors, and there is no report regarding the impact of changing osmoloarity or total liquid volume injected subretincally on the retinal tissue over time. Besides, only a relatively small volume of fluid needs to be injected in small animals such as rats.

[0023] Larger eyes will require larger amounts of formulation to be effective and in the case of human use, osmotic stress may become significant. This concern was addressed in different contexts and also in the development of subretinal injection required to deliver gene therapy in subjects affected by LCA and RP, in which isotonic solutions were used.4344This is an unaddressed issue that requires reformulation of the suspension medium to allow use of P3HT NP in humans. However, a formulation change may cause problems with the physicochemical stability of the suspended particles that may precipitate in an ions-containing solution. This aspect has not been experimentally addressed in the known literature, but indicated in the applications US2019 / 0374477 and US2020 / 0113843. These applications suggest that different surfactants may stabilize P3HT NPs in suspension, but no experimental evidence has been provided and there is no clear indication of which surfactant may work and what the best concentration is. Furthermore, given the poor understanding of the relationship between P3HT NPs and media composition in determining its mechanism of action, the addition of surfactants may alter the hybrid interface between P3HT NPs and neurons, thereby potentially reducing or nullify their effectiveness in restoring vision.

[0024] It is also worth noting that these applications never mention the final concentration of the P3HT NPs in the injected formulation. The concentration is indicated in other papers by the same authors as being 1 mg / ml.27’39No other concentrations have been tested or reported in any publications present in the scientific literature. Moreover, these applications never mention the actual volume of P3HT NPs effectively injected per animal.

[0025] Larger eyes, such as in human or larger mammals, may show sectorial degeneration of photoreceptors, with areas of atrophy in the retina coexisting with areas in relatively normal conditions. Therefore, appropriate targeting of the injection site with a tailored volume of P3HT NPs aqueous suspension will be required to deliver maximal effects in the dysfunctional retinal sectors, rather than a complete and unselected coverage of the full retina. No evidence of exploring this approach with P3HT NPs was made, nor any data are available in mammals larger than rats supporting this tenet.

[0026] In conclusion, there are still some problems related to the preparation of effective formulations of P3HT NPs especially for human use: (a) the osmolarity of the current formulations, which is unsuitable for human use, as the known aqueous suspensions are hypotonic; (b) the instability of the nanoparticles in saline solutions, which have a tendency to precipitate in physiological solutions, (c) the unknown capacity of the P3HT NPs when suspended in a new formulation to recover vision and to improve retina functions when injected in the subretinal space as suspension.

[0027] Summary of the disclosure

[0028] The present disclosure aims at overcoming the prior art shortcomings by providing a composition of poly(3-hexylthiophene) (P3HT) nanoparticles (NPs) that is isotonic - hence suitable for human or animal use - and at the same time stable for the time needed to perform the surgical intervention.

[0029] In embodiment the nanoparticles can be nanoparticles with core@shell structure having a core comprising P3HT and a shell comprising oxidized poly(3-hexylthiophene), i.e. P3HT-S,S-dioxide (PTDO). These nanoparticles are indicated as P3HT@PTDO-NPs.

[0030] In particular, the present disclosure refers to a composition comprising poly(3-hexylthiophene) nanoparticles suspended in a saline solution comprising a stabilizing agent selected from a non-ionic surfactant, a water-soluble polymer having high intrinsic viscosity and a combination thereof.

[0031] The preferred water-soluble polymer is hyaluronic acid.

[0032] The saline solution is an aqueous solution comprising at least sodium ions and chloride ions. In an embodiment of the disclosure the saline solution further comprises at least one of: magnesium ions, calcium ions, potassium ions, and combination thereof.

[0033] The new formulation mimics the subretinal extracellular medium composition and aims to reduce the osmotic stress produced by subretinal injection of hypotonic solution (i.e., aqueous solution) used to suspend P3HT NPs in the prior art.

[0034] The formulation has demonstrated an improved effectiveness in restoring a visual response in the RCS rat model of blindness, and potentially in the human retinal dystrophies such as retinitis pigmentosa (RP) and macular degeneration (AMD) with respect to the known P3HT NPs suspended in water. In particular, the formulation has shown to increase Visual Evoked Potential (VEP) amplitude, in the rat blindness model surprisingly better than the known aqueous suspension. VEP signals critically depend on the functional status of the retinal cells and neurons that project to the cortex, being an important instrumental tool for studying retinal dystrophies and ocular neurodegenerative diseases.

[0035] The reason of this improvement is non-obvious and not fully understood. The improvement was also non-predictable a priori considering that any formulation change may cause interactions between the particles and the used surfactants or excipients changing the photophysical properties of the same which influences their biological activity.45

[0036] Provided is also a kit for preparing the isotonic and stable composition of the disclosure, which comprises a part A and a part B. Part A comprises an aqueous suspension of P3HT NPs and part B comprises an aqueous solution comprising at least sodium ions and chloride ions and, optionally, at least one of: magnesium ions, calcium ions, potassium ions, and combination thereof, together with at least one stabilizing agent.

[0037] Part A and part B are mixed before application in the eye, which is preferably performed by subretinal injection.

[0038] The inventors have also demonstrated that suspension of P3HT NPs in aqueous solution recover vision in rat models even when the concentration of the P3HT NPs is lower than the known 1 mg / ml. Concentration ranges of 0.1 mg / l - 0.8 mg / l in the composition according to disclosure are deemed to be as effective as the known concentration of 1 mg / ml.

[0039] Given the uncertainty of the mechanism of action of the P3HT particles in the retina, there is no prior indication in literature regarding a range of concentrations that can work, underlining the innovative aspect of this improvement.

[0040] BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1 - Behavioral Conditioning test of RCS rats injected in the subretinal space with P3HT NPs suspended either in water or in a solution containing hyaluronic acid (HA), (a) Scheme of the three phases; conditioning, cue, and context, (b) Freezing evaluation in no luminous stimulus condition (c) Freezing time in the dark and freezing in response to luminous stimulus., (n = 7, 12, and 14 for RCS, RCS+P3HT:H2O, and RCS+P3HT:HA, respectively, Student’s t test, *p<0.05).

[0042] Figure 2 - MTT viability assay on HEK293T cells after 4h incubation with P3HT NPs suspended in either the new formulation with HA, in water, and in an aqueous solution with Poloxamer P188.

[0043] Figure 3 - Electrophysiological recordings of Visual Evoked Potentials in RCS rats injected with either P3HT NPs suspended in water or in P3HT NPs suspended the new formulation containing HA (n = 7 and 12, respectively). Liquid Retina has a positive interaction coefficient with a p- value of 0.006.

[0044] Figure 4 - Instability index kinetic of P3HT particles in water and in different aqueous media containing hyaluronic acid (HA) and NaCL

[0045] Figure 5 - Z-size (positive bars), Z-potential (negative bars), and polidispersity index (dots) of P3HT NPs suspended in water and in selected surfactants at 0.01% and 0.001% W / V concentrations.

[0046] Figure 6 - Z-size (positive bars), Z-potential (negative bars), and polidispersity index (connected dots) of P3HT NPs dispersed in water and NaCI solution after addition of different surfactant at different storage times at 2-4 °C.

[0047] Figure 7 - Typical separation profile to study particles instability using transmittance.

[0048] Definitions

[0049] The expression “suspension” means a heterogeneous dispersion of nanoparticles in a medium.

[0050] As used herein, “visual deficit” means an impairment of both visual acuity and binocularity.

[0051] As used herein, “blindness” means a disease state of low or absent vision, preferably said blindness is secondary to the degeneration of retinal rods and / or cone photoreceptors.

[0052] As used herein, “high sensitivity” of the eye means the ability of our retina to perceive the visual field in ambient light as well as at low luminance levels.

[0053] As used herein, “visual performance” means the ability to perceive visual information with high spatial resolution and contrast sensitivity.

[0054] As used herein, the term “photoreceptors” refers to the cells that begin the process of seeing by absorbing and converting light into electrical signals. The resulting electrical activation / inhibition of the intermediate layer of neurons (bipolar cells) that is preprocessed by the retinal circuits is conveyed to the innermost layer (retinal ganglion cells) that transmit the visual information to the brain through the optic nerve. There are two general types of photoreceptors, called rods and cones. In humans, rods are in the outer regions of the retina and allow us to see in dim light. Cones reside mostly in the central portion of the retina and allow us to perceive fine visual detail and color.

[0055] As used herein, the terms “treatment” or “treating” refer to the medical management of a subject with the intent to cure, ameliorate, stabilize, or prevent a condition or disorder. Therefore, in the contest of the present disclosure treating means also rescuing or ameliorating or curing.

[0056] As used herein, the term “applying” refers to any method of providing or administering a composition and / or pharmaceutical composition thereof to a subject, preferably applying by microinjection into the subretinal space. The path to the subretinal space could be through the corpus vitreous, or through a less invasive scleral flap.

[0057] As used herein, the term “therapeutically effective amount” refers to an amount that is sufficient to achieve the desired therapeutic result or to have an effect on undesired symptoms but is generally insufficient to cause adverse side effects.

[0058] As used herein, the terms “subject” or “subject in need thereof” refer to a target of administration, which optionally displays symptoms related to a particular disease, condition, disorder, or the like. The subject(s) (or individual) of the herein disclosed methods can be human or non-human.

[0059] As used herein, the term “hydrodynamic diameter” refers to the nanoparticle diameter measured by a light scattering apparatus. This value is a standard figure of merit for the particle size that however exceeds the physical particle size, as measured for instance by transmission electron microscopy (TEM). The difference is due to a surface layer covering the particle and to the polarization of the medium.

[0060] As used herein, the term “Z-potential” refers to the potential difference between the dispersion medium and the stationary layer of fluid attached to the dispersed particle.

[0061] As used herein, the term “polydispersity index” (PDI) refers to a standard figure of merit characterizing the particle size distribution. It is calculated by taking the size distribution of a sample and dividing its standard deviation by its mean.

[0062] As used herein, the term “microinjection” refers to the administration of a substance using a microsyringe to slowly and regularly inject microliter volumes at microscopic level. As used herein, the term “retinal degeneration” refers to the apoptotic degeneration of photoreceptors in the retina, a phenomenon that eventually leads to total blindness.

[0063] As used herein, the term “subretinal space” or “subretinal region” refers to the area between the retina pigment epithelium (RPE) and the bipolar cell layer.

[0064] The term “high intrinsic viscosity” means an intrinsic viscosity higher than 0.02 m3 / kg measured using either Huggins or Kraemer equations.

[0065] DETAILED DESCRIPTION OF THE DISCLOSURE

[0066] A first aspect of the disclosure refers to a composition comprising a suspension of nanoparticles (NPs) of poly-(3-hexylthiophene) (P3HT-NPs) in an aqueous solution comprising at least sodium ions and chloride ions together with at least one stabilizing agent selected from: a water-soluble polymer and / or a non-ionic surfactant selected from poloxamer P188, Tween 80, Kollipor P407, Kollipor HS 15, Brij35, Cremophor RH40, Tween 20, Tween 60, Oramix CG110, Oramix NS10 and combination thereof.

[0067] The composition is referred to as Liquid Retina (LR) from now on.

[0068] The P3HT-NPs are characterized by a diameter ranging from 150 to 230 nm. Said diameter is preferably a hydrodynamic diameter (HD) as defined above.

[0069] According to a preferred embodiment, the P3HT-NPs are characterized by a polydispersity index (PDI) comprised between 0.01 and 0.8, preferably between 0.02 and 0.6, more preferably between 0.02 and 0.4.

[0070] According to a preferred embodiment, the P3HT-NPs, are characterized by a Z-potential from - 55 to 25 mV.

[0071] P3HT-NPs absorb the wavelength of visible light, preferably ranging from 495 to 620 nm, more preferably from 460 to 640 nm, still more preferably from 400 to 700 nm.

[0072] In a preferred embodiment, the P3HT-NPs, absorb the light with a peak in the green-orange region. According to an embodiment, the P3HT-NPs are prepared using methods known in the art, for example disclosed in US2020 / 0113843 here incorporated by reference or using microfluidics.

[0073] In an embodiment, the P3HT-NPs are functionalized by transforming thiophene units into thiophene-S,S-dioxide (TDO) ones, thus leading to the formation of a shell of n-type polymeric chains (namely, PTDO) on the P3HT-NPs surface.

[0074] The functionalization method is known from F. Di Maria, A. Zanelli, A. Liscio, A. Kovtun, E. Salatelli, R. Mazzaro, V. Morandi, G. Bergamini, A. Shaffer, S. Rozen, ACS Nano 2017, 11 , 1991 -1999.

[0075] This chemical methodology allows the synthesis of all-organic core@shell nanostructures (P3HT@PTDO), in which acceptor (PTDO present on the shell) and donor (P3HT present in the core) materials are in intimate contact and spatially localized in a single nanoarchitecture.

[0076] The nanoparticles used in the present invention can be nanoparticles with core@shell structure having a core comprising P3HT and a shell comprising oxidized poly(3-hexylthiophene), i.e. P3HT-S,S-dioxide (PTDO). The nanoparticles concentration in the composition is from 0.1 to 0.8 mg / ml, preferably from 0.1 to 0.6 mg / ml.

[0077] In one embodiment, the aqueous solution in which the nanoparticles are suspended is a saline solution, i.e. a solution comprising sodium ions and chloride ions.

[0078] The sodium ions are present in a preferred concentration of 0.1 - 0.4 mol / L The chloride ions are present in preferred concentration of 0.1 - 0.4 mol / L

[0079] In another embodiment, the aqueous solution further comprises at least one of: magnesium ions, calcium ions, potassium ions and a combination thereof.

[0080] In another embodiment, the composition comprises sodium ions, chloride ions and magnesium ions.

[0081] In another embodiment, the composition comprises sodium ions, chloride ions and calcium ions.

[0082] In another embodiment, the composition comprises sodium ions, chloride ions and potassium ions.

[0083] In a preferred embodiment, the composition comprises sodium ions and chloride ions, and further comprises magnesium ions and / or calcium ions and / or potassium ions.

[0084] In another embodiment, the composition further comprises acetate ions and / or citrate ions and / or carbonate ions, in addition to sodium and chloride ions and at least one of magnesium ions, calcium ions, potassium ions and a combination thereof.

[0085] In an embodiment, the composition comprises sodium ions, chloride ions, magnesium ions, calcium ions and potassium ions and, preferably, acetate and / or citrate ions and / or carbonate ions.

[0086] The magnesium ions are preferably present in a concentration of 0.0005 mol / L - 0.005 mol / L.

[0087] The calcium ions are preferably present in a concentration of 0.0005 mol / L

[0088] - 0.007 mol / L.

[0089] The potassium ions are preferably present in a concentration of 0.0005 mol / L - 0.03 mol / L.

[0090] The acetate ions, if present, are preferably in a concentration of 0.01 mol / L

[0091] - 0.2 mol / L

[0092] The citrate ions, if present, are preferably in a concentration of 0.001 mol / L

[0093] - 0.007 mol / L

[0094] The carbonate ions, if present, are preferably in a concentration of 0.01 mol / L - 0.2 mol / L

[0095] The sodium ions can derive from sodium chloride and / or from sodium acetate and / or sodium citrate and / or sodium carbonate and / or any other pharmaceutically acceptable salt which can provide sodium ions in the concentration ranges indicated above.

[0096] The chloride ions can derive from sodium chloride and / or potassium chloride and / or calcium chloride and / or magnesium chloride and / or any other pharmaceutically acceptable salt which can provide chloride ions in the concentration ranges indicated above.

[0097] The magnesium ions derive from magnesium chloride and / or magnesium chloride hexahydrate and / or any other pharmaceutically acceptable salt which can provide magnesium ions in the concentration ranges indicated above.

[0098] The potassium ions derive from potassium chloride and / or any other pharmaceutically acceptable salt which can provide potassium ions in the concentration ranges indicated above.

[0099] Acetate, citrate and carbonate ions can derive, for example, from sodium acetate, sodium acetate trihydrate, sodium citrate, sodium citrate dihydrate, sodium carbonate and / or any other pharmaceutically acceptable salt which can provide acetate, citrate and carbonate ions in the concentration ranges indicated above.

[0100] Carbonate, acetate and / or citrate salts are used to regulate the pH of the composition, which is between 6 and 8, preferably between 6.8 and 7.4.

[0101] The osmolarity of the composition is between 200-400 mOsm / L, preferably between 280-320 mOsm / L. The presence of at least one stabilizing agent in the composition prevents precipitation of the nanoparticles in salt solution. While the P3HT-NPs remain in suspension in an aqueous solution, they precipitate when suspended in a salt solution, forming aggregates.

[0102] The addition of a stabilizing agent in the aqueous salt solution prevents precipitation and aggregation of the P3HT-NPs, and helps stabilizing the suspension for a long time, preferably for up to 1 year.

[0103] The water-soluble polymer having high intrinsic viscosity is preferably hyaluronic acid and / or salts thereof, polyvinyl alcohol (PVA) and / or polyvinyl pyrrolidone (PVP).

[0104] The intrinsic viscosity of the water-soluble polymer is between 0.02 and 3 m3 / kg. The preferred non-ionic surfactant is Poloxamer P188, Tween 80, Oramix CG110.

[0105] The concentration of the stabilizing agent is 0.005-5 mg / ml, preferably 0.005-0.015 mg / ml or 0.9 - 1 .1 mg / ml.

[0106] In a preferred embodiment, the composition comprises a suspension of nanoparticles (NPs) of poly-(3-hexylthiophene) (P3HT-NPs) and / or a suspension of core@shell P3HT@PTDO-NPs in an aqueous solution comprising at least sodium ions and chloride ions and hyaluronic acid (or salts thereof) and / or poloxamer P188 and / or Tween and / or PVA. The composition further comprises at least one of magnesium ions, calcium ions, potassium ions and a combination thereof. Preferably, the composition comprises the nanoparticles in concentration of from 0.1 to 0.8 mg / ml, preferably from 0.1 to 0.6 mg / ml. Preferably, the composition further comprises acetate and / or citrate and / or carbonate ions.

[0107] The composition so far described is prepared by mixing, preferably immediately before use, at least two compositions.

[0108] One composition is a suspension of P3HT-NPs and / or P3HT@PTDO-NPs in water comprising a concentration of nanoparticle which is double the one that is obtained in the final composition.

[0109] In particular, the concentration of P3HT-NPs and / or P3HT@PTDO-NPs in the initial aqueous suspension is from 0.2 to 1 .6 mg / ml, preferably from 0.2 to 1 .2 mg / ml.

[0110] The other composition is an aqueous solution, as previously described, comprising at least sodium ions and chloride ions together with at least one stabilizing agent selected from: hyaluronic acid, a non-ionic surfactant, a water-soluble polymer and a combination thereof.

[0111] The composition further comprises at least one of magnesium, potassium, calcium, acetate, citrate and carbonate ions.

[0112] The concentration of each ingredient is double the one that is obtained in the final composition.

[0113] In particular, the sodium ions are present in a preferred concentration of 0.2 - 0.8 mol / L The chloride ions are present in preferred concentration of 0.2 - 0.8 mol / L

[0114] The magnesium ions, are preferably present in a concentration of 0.001 mol / L - 0.01 mol / L.

[0115] The calcium ions are preferably present in a concentration of 0.001 mol / L - 0.014 mol / L.

[0116] The potassium ions are preferably present in a concentration of 0.001 mol / L - 0.06 mol / L.

[0117] The acetate ions, if present, are preferably in a concentration of 0.02 mol / L - 0.4 mol / L

[0118] The citrate ions, if present, are preferably in a concentration of 0.002 mol / L - 0.014 mol / L

[0119] The carbonate ions, if present, are preferably in a concentration of 0.02 mol / L - 0.4 mol / L

[0120] The two compositions are mixed in a proportion of 1 part of the P3HT NPs and / or P3HT@PTDO-NPs suspension and 1 part of the aqueous solution of salts and stabilizing agent. After mixing, the final composition comprises the ingredients, including the nanoparticles, in concentrations that are half the starting ones.

[0121] The mixture is preferably made immediately before use, i.e. before injection in the eyes of a patient, but can also be mixed before use and stored for some time especially when the stabilizing agent is a non- ionic surfactant or a high intrinsic viscosity water soluble polymer.

[0122] Therefore, another embodiment of the disclosure refers to a kit comprising a part A and a part B, wherein part A comprises an aqueous suspension of poly(3-hexylthiophene) (P3HT) nanoparticles and / or P3HT@PTDO nanoparticles and part B comprises an aqueous solution comprising at least sodium ions and chloride ions together with at least one stabilising agent selected from: a non-ionic surfactant selected from poloxamer P188, Tween 80, Kollipor P407, Kollipor HS 15, Brij35, Cremophor RH40, Tween 20, Tween 60, Oramix CG110, Oramix NS10 and combination thereof; and / or a water-soluble polymer having high intrinsic viscosity and a combination thereof.

[0123] The kit can further comprise one or more other compositions containing pharmaceutically acceptable excipients that can be added to part A and B to make the final formulation for ophthalmic use. For example, the further compositions can be aqueous solutions of one or more excipients or one or more excipients in a solid form, which can be added to the mixture of A and B. Pharmaceutically acceptable excipients are, for example, any one of anti-inflammatory, astringent drugs, preferably selected from: neostigmine methylsulfate, corticosteroids, cortisol derivatives, s-amino caproic acid, allantoin, berberine chloride, zinc sulfate, lysozyme chloride, sodium azulene sulfonate, dipotassium glycyrrhizinate and combinations thereof; antiallergic agents, preferably selected from: diphenhydramine hydrochloride, isopenzyl hydrochloride, chlorpheniramine maleate, sodium cromoglycate and combinations thereof; vitamins other than pyridoxine hydrochloride, preferably selected from: vitamin B2, vitamin B12, vitamin A, vitamin E, calcium pantothenate and combinations thereof; amino acids, preferably selected from: potassium L-aspartate, magnesium L- aspartate, aminoethylsulfonic acid and combinations thereof; sulfa drugs, preferably selected from: sulfamethoxazole, sulfisoxazole, sulfisomidine and combinations thereof; bacteriocides, preferably selected from: sulfur, isopropylmethyl phenol, hinokithiol and combinations thereof; topical anesthetics, preferably selected from: lidocaine, lidocaine hydrochloride, procaine hydrochloride, dibucaine hydrochloride and combinations thereof; inorganic salts, preferably selected from: potassium chloride, sodium chloride, sodium bicarbonate and combinations thereof; thickening agents, preferably selected from: polyvinyl alcohol, polyvinyl pyrrolidone, carboxymethyl cellulose, hyaluronic acid, glucose and combinations thereof.

[0124] The one or more excipients can also be pre-added in part A and / or B.

[0125] The kit can further contain instructions for use of part A and B and any other further parts included in the kit, for example instructions for preparing the composition of the disclosure by mixing parts A and B, and possibly adding one or more excipients present in the kit in solid form or dissolved in aqueous solution.

[0126] Once parts A and B are mixed the obtained composition mimics the intra- retinal liquid composition and it is isotonic with such intraretinal liquid, thus reducing the hypotonic shock produced by the known aqueous suspensions of nanoparticles during subretinal injection in the eye of a patient. For this reason, the composition of the disclosure can also be called Liquid Retina (LR).

[0127] The Liquid Retina can be used in a method for treating a visual deficit in a subject in need thereof, wherein the method comprises at least one step of applying a therapeutically effective amount of the Liquid Retina to the eye of said subject.

[0128] The method of the disclosure allows completely or at least partially curing or rescuing said visual deficit or even ameliorating said visual deficit in the subject in need thereof.

[0129] The Liquid Retina can be also useful to rescue light sensitivity and / or visual performances of a malfunctioning eye of a subject in need thereof.

[0130] A further aspect of the present disclosure refers to a method for treating blindness, preferably secondary to the degeneration and / or malfunction of eye photoreceptors, in a subject in need thereof comprising at least one step of applying a therapeutically effective amount of the Liquid Retina to the eye of said subject.

[0131] Therefore, the Liquid Retina as here disclosed can be also defined or considered a substitute of degenerated and / or impaired photoreceptors of the eye.

[0132] In another aspect, the disclosure refers to a method of treating an ocular disorder selected from retinal dystrophies and retinal neurodegenerative diseases comprising at least one step of applying a therapeutically effective amount of the Liquid Retina to the eye of said subject. Retinal dystrophies are a group of genetic disorder typical of the youngadult age, which include, among others, Retinitis Pigmentosa (RP), Leber Congenital Amaurosis (LCA), Achromatopsia, Cone Rod Dystrophy.

[0133] Retinal neurodegenerative diseases are a group of disorders, typical of adult-elderly age, defined by different degrees of degeneration of both photoreceptors and retinal neurons (e.g., ganglion, bipolar, amacrine cells), which include age-related macular degeneration (AMD), diabetic retinopathy and glaucoma.

[0134] In a preferred embodiment, retinitis pigmentosa (RP) or macular degeneration (AMD) are treated with the Liquid Retina of the disclosure by applying a therapeutically effective amount of the Liquid Retina to the eye of a subject in need thereof.

[0135] The disclosure refers also to the Liquid Retina for use as medicament, in particular for treating a visual deficit.

[0136] The Liquid Retina can be used to rescue light sensitivity and / or visual performances of a malfunctioning eye, for treating blindness, preferably secondary to the degeneration and / or malfunction of eye photoreceptors, and / or to substitute degenerated and / or impaired photoreceptors of an eye.

[0137] The Liquid Retina is also used for the treatment of retinal dystrophies selected from: Retinitis Pigmentosa (RP), Leber Congenital Amaurosis (LCA), Achromatopsia and Cone Rod Dystrophy.

[0138] The Liquid Retina is also used for the treatment of retinal neurodegenerative diseases selected from age-related macular degeneration (AMD), diabetic retinopathy and glaucoma.

[0139] In another embodiment, the invention refers to the use of a high intrinsic viscosity water soluble polymer and / or a non-ionic surfactant to stabilize a suspension of poly(3-hexylthiophene) (P3HT) nanoparticles and / or P3HT@PTDO nanoparticles in an aqueous solution comprising at least sodium ions and chloride ions and optionally at least another ion as described previously. The non-ionic surfactant is selected from poloxamer P188, Tween 80, Kollipor P407, Kollipor HS 15, Brij35, Cremophor RH40, Tween 20, Tween 60, Oramix CG110 and Oramix NS10.

[0140] Another advantage of the stabiliser is that it increases the final viscosity of the formulation, which reduces the spread of the fluid once it is injected into a specific area of the retina. The small injected volume and intrinsic viscosity of the composition will allow a predetermined sub-region of the retina to be targeted without spreading across the entire retina. At the same time, these compositional characteristics will reduce reflux of the injected formulation from the subretinal space into the vitreous. Early experimental results support these features. These features of selective targeting are of potential interest for adapting the implantation technique to the needs of the patient. In patients with retinal dystrophies and / or neurodegenerative retinal diseases, specific subregions are affected by photoreceptor degeneration or atrophy. Low-volume, high-viscosity injections, such as Liquid Retina, would appropriately target the atrophic areas while sparing the normally functioning areas, resulting in more effective therapeutic outcomes.

[0141] EXPERIMENTAL DATA

[0142] P3HT NPs recover vision in rat RCS model of blindness when the new concentration of 0.2 mg / ml is compared to the previously reported 1 mg / ml in either water or as Liquid Retina (LR)

[0143] The RCS rats were divided into 3 groups: (a) control blind RCS rats, (b) blind RCS rats implanted with P3HT NPs suspension at a concentration of 0.2 mg / ml in the new formulation (LR) that feature hyaluronic acid as stabilizing agent (P3HT:HA), and (c) blind RCS rats implanted with P3HT NPs suspended in water at a concentration of 0.2 mg / ml (P3HT:H2O).

[0144] The description of the LR formulation used in the experiment is reported in Errore. L'origine riferimento non e stata trovata.. It consisted of a kit with two different solutions with different compositions, part A and B, which were mixed immediately before their subretinal injection.

[0145] Table 1 Composition of Liquid Retina formulation

[0146] Part A and B are mixed before use in a proportion of 1 :1. Therefore, the concentration of the nanoparticles of part A is halved in the final composition, being 0.2 mg / ml.

[0147] The recovery of vision in the 3 groups of RCS rats was studied 1 month after surgery using Fear Conditioning test.27Briefly, RCS rats were conditioned to associate the light stimulus with an unconditional painful stimulus that elicit a freezing response during the leaning phase of the test (Figure 1a). During the cue phase, animals were exposed to repeated conditioned light stimuli resulting in a significant increase of their freezing response when compared with behavior in the dark.

[0148] RCS injected subretinally with either P3HT:H2O or P3HT:HA show a significant increase in freezing response to the light stimulus when compared to control blind RSC rats (Figure 1c).

[0149] Figure 1d shows that the freezing response was not related to the context they are exposed to, confirming the correlation between light stimulus and freezing response in RCS rats treated with P3HT NPs.

[0150] The results of this vision-dependent behavioral test demonstrate that LR, the composition of the disclosure, is effective in restoring vison in blind RCS rats, and that a concentration of 0.2 mg / ml of P3HT NPs is capable of restoring vision independently of the formulation used, showing a significant effect at a concentration that was different and lower than the 1 mg / ml described in the literature and in other patents .2739

[0151] Liquid Retina (LR) characterization: Optimal stability over time and clean preliminary in vitro cytotoxicity tests

[0152] The Liquid Retina (LR) is a bicomponent liquid device to be injected inside the subretinal space of the eye to recover vision in blind patients affected by retinal dystrophies or retinal neurodegenerative disorders. The LR composition is reported in Errore. L'origine riferimento non e stata trovata., consisting of two solutions, part A that contains the P3HT NPs in suspension, and part B, that contains salts mimicking the subretinal liquid ionic profile when appropriately mixed with par A. According to the treatment protocol, part A and part B must be mixed immediately before their use. The aim of this study was to characterize the maintenance of stability in suspension of P3HT NPs in the part A (also defined as ‘shell life’).

[0153] Table 2 reports the properties of part A measured every 3 months up to 9 months while kept in a shelf at 4 °C and at 25 °C. There was no major change in the properties, thereby demonstrating the stability of the P3HT NPS suspension at both temperatures.

[0154] Table 2 Recording of various parameters for stability testing

[0155]

[0156] A non-GLP cytotoxicity test was performed comparing different formulations. Four groups were tested in vitro: (a) P3HT NPs as LR with high concentration of hyaluronic acid, (b) P3HT NPs suspended in water, (c) P3HT NPs suspended in a poloxamer P188 solution, (d) control solutions of NaCI as controls. The MTT test was performed on HEK cells. The results are shown in Figure 2. No toxicity effects were observed with any of the treatment groups containing P3HT NPs at any time, showing no detectable effect on the viability of HEK cells. This result points to a low cytotoxic liability effects of P3HT NPs.

[0157] Liquid Retina comprising P3HT NPs at 0.2 mg / ml was found to surprisingly increase Visual Evoked Potential (VEP) amplitude in the rat RP model better than the known formulation of P3HT NPs in water The functional retinal effects of P3HT NPs subretinal injections in blind RCS rats when performed either as water suspension or as LR was tested. Two months after subretinal injections, electrophysiological recordings of Visually Evoked Potentials (VEP) were performed in response to pattern light stimuli with different spatial frequencies in RCS rats injected with either LR or P3HT NPs in water. Results indicated that VEP were significantly higher in RCS rats implanted with LR when compared to RCS rats implanted with P3HT NPs in water for every spatial frequency. Moreover, LR-treated RCS rats were able to respond to 0.2 cpd patterns of stimuli, while RCS rats treated with P3HT NPs in water were not able to respond to the 0.2 cpd patterns (Figure 3). Linear fit of the VEP amplitudes was used to extract the visual acuity from x-intercept: its implementation showed that LR treated RCS rats showed an acuity of 0.39 cpd, while RCC rats treated with P3HT NPS in water showed an acuity of 0.17 cpd. A linear regression introducing an interaction factor for the use of Liquid Retina was performed. The regression used a robust algorithm with a trimmed mean weighting. The Liquid Retina interaction is positive with a p-value of 0.006. These results indicate a superiority of LR over P3HT NPs in water in determining retina-dependent visual signal transfer to the visual cortex of the brain. Although the precise reason of this surprising results is unknown, it is possible to suggest either a better retinal cells response due to the more physiological profile of the LR composition, or a better distribution of P3HT NPs in the retina surface due to the viscosity added by the hyaluronic acid present in the LR composition.

[0158] Stabilization effect of hyaluronic acid on P3HT NPs

[0159] Addition of salts to an aqueous solutions to optimize the use as injectable composition in human tissue is an obvious approach to reduces osmotic cellular stress that a pure water formulation elicits in tissue due to non- isotonic conditions. However, we found that the simple addition of salts to a suspension of P3HT NPs in water produced an immediately precipitation of the P3HT NPs in aggregates at the bottom of the test tube. InTable 3 we reported a DLS analysis conducted before and after changing the medium and measuring the P3HT NPs suspension I precipitation. Any salt medium tested lead to an increase of Z-average due to aggregation and formation of voluminous agglomerates.

[0160] Table 3 DLS analysis of particles in different media

[0161]

[0162] The addition of hyaluronic acid modifies the viscosity of the solutions and greatly reduces the precipitation of nanoparticles. We have tested this instability studying the clarification of different samples. Table 4 report the results of such analysis. Particles in water show an increase in transmittance due to precipitation that leads to an almost transparent sample. When hyaluronic acid is added, the clarification is reduced meaning that the nanoparticles precipitation is hindered. The effect is significant both for high concentration (1 .5%) and low concentration (0.5%) of hyaluronic acid.

[0163] Table 4 Initial and final transmittance of P3HT NPs samples in different media

[0164] From the ratio between the measured transmittance at different times and the original transmittance of a sample, it is possible to extract the instability index. Results are reported in Figure 4. The results showed that samples containing hyaluronic acid had much lower changes in transmittance when compared with water or in NaCI over time, indicating that the presence of hjaluronic acid physically prevented aggregation, stabilizing the suspension.

[0165] Stabilization effect of Poloxamer P188

[0166] The concentration of the surfactant is important in defining the formulation of a medical device as the excipient can interact with the tissue and elicit inflammatory responses and / or biocompatibility issues. For this reason, Poloxamer P188, Tween80, Oramix CG110, and PVA have been studied at two different low concentrations, in particular at 0.01% and 0.001% W / V. These surfactants are known in medical industry and are particularly promising from a biocompatibility perspective. Poloxamer P188 is already used in Luxturna, a marketed subretinally administered gene therapy, confirming its viability as an excipient in a medical formulation. Figure 5 reports the main parameters of particles dispersed in NaCI solution containing the aforementioned surfactants at different concentrations stored for 1 month at 4 and 25 °C. At the lowest concentration tested, 0.001%, only Poloxamer P188 was able to maintain the stability of P3HT NPs either stored at 4 and 25 °C. Poloxamer P188 results as the best candidate to be added to P3HT-NPs preparation to improve their shelf-life stability, and to potentially improve their in vivo stability.

[0167] Stabilization effect of Tween 80 and PVA

[0168] Figure 5 shows that PVA type polymers act as good stabilizing agents; however high nanoparticles size was found due to its bulking properties. PEG-derivatives type of stabilizers, more specifically Tween80 and Poloxamer P188, yielded equal performances when used at 0.01% concentration. Stabilizing effect of Kollipor P407, Kollipor HS 15, Brij35, Cremophor RH40, Tween20, Tween60, Oramix CG110, Oramix NS10, PVP K30

[0169] Several surfactants were tested as stabilizers adding them to a water dispersion of nanoparticles in a 0.9% NaCI solution at a concentration of 0.5% W / V. Figure 6 reports the main parameters of nanoparticles inside different media at different times after production. P3HT nanoparticles in pure water are used as a control. These do not drastically alter their properties and show only minor deviations in size, PDI, and zeta potential. All the other samples are prepared dissolving a 0.5% W / V surfactant in an isotonic solution. Sodium alginate, pectin, and xyloglucane do not show stabilization effects and created agglomeration of particles into bigger clusters. All the other used surfactants do not show any major alteration of nanoparticles parameters over time. The results confirm that 0.5% Kollipor P407, Kollipor HS 15, Brij35, Cremophor RH40, Tween20, Tween60, Oramix CG110, Oramix NS10, and PVP K30 are all promising ingredients for maintaining P3HT NPs in the suspended form when formulated in isotonic media.

[0170] Methodology

[0171] Stability study of P3HT NPs in suspension. The analysis was conducted using an analytical centrifuge LUMiSizer LS651. The samples were held in a 2 mm optical path cuvette and centrifuged at 4000 rpm for 30 hours. The transmittance of the samples in the cuvette at different heights was continuously measured at 470 nm and is reported on the same graph at various time. Figure 7 reports a typical separation profile. On the x axis there is the position in the cuvette, while on the y axis there is the optical transmittance of the sample. The bottom profile is the starting one. As time passes by, the P3HT NPs start to precipitate, and the transmittance rises due to the decrease of concentration. From these curves it is possible to extract the instability index as the ratio between the starting transmittance and final transmittance. Experimental animals and ethical approval. All animal manipulations and procedures were performed in accordance with the guidelines established by the European Community Council (Directive 2012 / 63 / EU of 22 September 2010) and were approved by the Italian Ministry of Health (authorization n. 357 / 2019-PR from 17 / 05 / 2019, answer to 22418.101 .EXT.78 from 15 / 03 / 2021 ). RCS pink-eyed dystrophic rats, together with congenic non-dystrophic controls were provided by M. M. La Vail (Beckman Vision Centre, University of California San Francisco). Rat colonies were bred under standard conditions with ad libitum access to food and water under a 12 / 12-h light / dark cycle.

[0172] Surgical intervention. Three months-old RCS rats of either sex were anesthetized with an intraperitoneal injection of diazepam (10 mg / kg) followed by intramuscular administration of xylazine (5 mg / kg) and ketamine (50 mg / kg), and finally subjected to complete pupil dilation via 1% tropicamide eye drops. The subretinal injection of NPs was carried out as follows. A limbus-parallel conjunctiva dissection was performed with scissors 10 in the superior temporal quadrant. A small incision (about 0.5 mm) through the sclera and the choroid was carried out 1 mm from the limbus. Then, the retina was gently separated from the retinal pigment epithelium close to the incision using a small amount of viscoelastic material. P3HT NPs (10-20 pl at 0.2-1 .0 mg / ml), either mixed with Part B or diluted in equal volume with demineralized water, were then binocularly injected through a 38-gauge needle connected to syringe, paying attention to penetrate the subretinal space at the level of the viscoelastic material and to keep the needle tangential to the choroid in order to promote a circular flow that could detach the whole retina. The scleral incision was subsequently coagulated with diathermy and the conjunctiva was gently repositioned over the scleral wound. Surgical procedures were carried out in a sterile room using a Leica ophthalmic surgical microscope. During the whole procedure, the cornea was kept wet. At the end of the intervention, the status of the retina was evaluated by indirect ophthalmoscopy. Tobramycin and dexamethasone eye drops were administered for postoperative prophylaxis.

[0173] In vivo electrophysiology. Animals were anaesthetized with an intramuscular administration of xylazine (5 mg / kg) and ketamine (50 mg / kg) and placed on a stereotaxic frame. Anesthesia level was kept stable throughout the experiment and body temperature (37 °C) was continuously monitored. A hole was drilled in the skull, corresponding to the binocular portion of V1 (Oc1 B). After exposure of the brain surface, the dura mater was gently removed, and a micropipette (2-4 MQ) filled with NaCI (3 M) was inserted into the cortex 5 mm from A (intersection between the sagittal and the lambdoid sutures) and 400 pm in depth. Both eyes were fixed and kept wet and open throughout the analysis by means of adjustable metal rings. Visual acuity was measured recording visually evoked potentials (VEPs). Signals (average of 50 sweeps) were amplified, band-pass filtered at 0.1-100 Hz, digitized and analyzed with a custom MATLAB application. The same software enabled also the presentation of the desired visual stimuli, represented by vertical gratings from a CRT monitor (100 % contrast) at different spatial frequencies (0.017-1 CPD, 1 Hz) and a 120 cd / m2luminance approximatively 20-25 cm from the animal’s eyes. As for detection of VEPs, a deflection of the basal electrical signal in Oc1 b was considered physiologically relevant when it was more than twice the s.d. of the noise.

[0174] Light-cued classical conditioning. 1 month after surgery, the classical conditioning paradigm was performed in an environmental chamber equipped with a grid to deliver the shock (Med Associated Inc.). A camera mounted on the front door recorded test sessions, which were automatically scored using the integrated software for the identification and quantification of behavioral freezing. The adopted protocol was composed of 3 phases: I. The Conditioning session consisted of 2 min of habituation in which animals freely moved to explore the environment. Immediately after, a sequence of seven repetitions of white light flashes (22 lux at 5 Hz; 2 s on I 2 s off repeated for 5 times) serving as the conditioning stimulus (CS) with 60 s off between each CS. During the last 2 s light on, a mild foot shock (0.5 mA) was delivered as the unconditioned stimulus (US). Each rat received seven CS-US pairings separated by intervals of variable duration. To evaluate the US-CS associative learning, we quantified the freezing behavior during each US-CS pairing. II. The Cue test session took place the day after the conditioning session in the same apparatus. To avoid chamber-US association and only evaluate the CS-US association, the environment was altered by covering the grid floor with a smooth white plastic sheet and replacing the arena with black and white stripped walls. In addition, a new aromatic odor (Vanillin, Sigma- Aldrich) and two wired cups were introduced in the chamber. After 5 min habituation to the new chamber, the test began. After 2 min in the dark without stimulation, each animal received 3 min of continuous CS. To evaluate if rats were able to perceive the light stimulus, the freezing behavior was quantified during the 2 min in the dark and during the 3 min of CS. III. The Context session took place the day after the Cue test session in the same chamber as the conditioning session. Each rat was placed in the chamber for 5 min in the absence of CS and US, during which freezing behavior was scored. Before each test session, rats were dark-adapted for 1 h. The tasks were conducted in the dark. For each session of the test, the time percentage of freezing behavior was expressed as freezing time (s) / total time (s) of the session.

[0175] In vitro citotoxicity. The citotoxicity has been estimated using a cell proliferation MTT test (CyQuant MTT Cell Proliferation Assay Kit, Thermo Fisher Scientific, REF. V3154) on immortalized HEK-293T (ATCC) cells. The test is based on the capacity of living cell to mediate the conversion of (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), soluble in water, into formazan crystals. Cells were plated in 96-well clear microplates (Corning # 353072) at a density of 5k cells for 100 pl. The cells were incubated in MEM medium without phenol red indicator (Gibco # 51200-038) supplemented with 10% FBS (v / v), 100 U / ml of penicillin, 1 mg / ml of streptomycin, and 20 nM L- Glutamine (Merck # G6784) (MEMc). The incubation lasted 24 hours at 37 °C, 95% humidity and 5% CO2. The MTT test was conducted on two independent cell preparations. Cells were mixed with P3HT nanoparticles at 6 different concentrations varying the addition volume and were incubated for 4 hours. Once the incubation was done, formazan absorbance was recored using a plate reader (@540 nm, 20 illuminations, Tecan Infinite-500 plate reader). Vitality is expressed as the ratio between the absorbance of the preparation treated with the particles and the nontreated one.

[0176] References

[0177] (1 ) Chawla, H.; Vohra, V. Retinal Dystrophies; StatPearls Publishing, 2023.

[0178] (2) Marchesi, A.; Rigante, D.; Cimaz, R.; Ravelli, A.; Tarissi De Jacobis, I.; Rimini, A.; Cardinale, F.; Cattalini, M.; De Zorzi, A.; Dellepiane, R. M.;

[0179] Salice, P.; Secinaro, A.; Taddio, A.; Palma, P.; El Hachem, M.; Cortis, E.; Maggio, M. C.; Corsello, G.; Villani, A. Revised Recommendations of the Italian Society of Pediatrics about the General Management of Kawasaki Disease. Ital. J. Pediatr. 2021 , 47 (1 ), 16. https: / / doi.org / 10.1186 / s13052- 021 -00962-4.

[0180] (3) Cross, N.; Van Steen, C.; Zegaoui, Y.; Satherley, A.; Angelillo, L. Retinitis Pigmentosa: Burden of Disease and Current Unmet Needs. Clin. Ophthalmol. 2022, Volume 16, 1993-2010. https: / / doi.Org / 10.2147 / OPTH.S365486. (4) World Report on Vision. 2019, 180.

[0181] (5) Grover, S.; Fishman, G. A.; Alexander, K. R.; Anderson, R. J.; Derlacki, D. J. Visual Acuity Impairment in Patients with Retinitis Pigmentosa. Ophthalmology 1996, 703 (10), 1593-1600. https: / / doi.Org / 10.1016 / S0161 -6420(96)30458-2.

[0182] (6) Vyawahare, H.; Shinde, P. Age-Related Macular Degeneration: Epidemiology, Pathophysiology, Diagnosis, and Treatment. Cureus 2022. https: / / doi.org / 10.7759 / cureus.29583.

[0183] (7) Testa, F.; Melillo, P.; Di Iorio, V.; lovino, C.; Farinaro, F.; Karali, M.; Banfi, S.; Rossi, S.; Della Corte, M.; Simonelli, F. Visual Function and Retinal Changes after Voretigene Neparvovec Treatment in Children with Biallelic RPE65-Related Inherited Retinal Dystrophy. Sci. Rep. 2022, 12 (1 ), 17637. https: / / doi.org / 10.1038 / s41598-022-22180-6.

[0184] (8) Martinez-Fernandez De La Camara, C.; Cehajic-Kapetanovic, J.; MacLaren, R. E. RPGR Gene Therapy Presents Challenges in Cloning the Coding Sequence. Expert Opin. Biol. Ther. 2020, 20 (1 ), 63-71 . https: / / d0i.0rg / l 0.1080 / 14712598.2020.1680635.

[0185] (9) Georgiadis, A.; Duran, Y.; Ribeiro, J.; Abelleira-Hervas, L.; Robbie, S. J.; Sunkel-Laing, B.; Fourali, S.; Gonzalez-Cordero, A.; Cristante, E.; Michaelides, M.; Bainbridge, J. W. B.; Smith, A. J.; Ali, R. R. Development of an Optimized AAV2 / 5 Gene Therapy Vector for Leber Congenital Amaurosis Owing to Defects in RPE65. Gene Ther. 2016, 23 (12), 857- 862. https: / / d0i.0rg / l 0.1038 / gt.2016.66.

[0186] (10) Cheng, S.-Y.; Punzo, C. Update on Viral Gene Therapy Clinical Trials for Retinal Diseases. Hum. Gene Ther. 2022, 33 (17-18), 865-878. https: / / d0i.0rg / l 0.1089 / hum.2022.159.

[0187] (11 ) Khanani, A. M.; Thomas, M. J.; Aziz, A. A.; Weng, C. Y.; Danzig, C. J.; Yiu, G.; Kiss, S.; Waheed, N. K.; Kaiser, P. K. Review of Gene Therapies for Age-Related Macular Degeneration. Eye 2022, 36 (2), 303- 311 . https: / / d0i.0rg / l 0.1038 / S41433-021 -01842-1 .

[0188] (12) Song, C.; Conlon, T. J.; Deng, W.-T.; Coleman, K. E.; Zhu, P.; Plummer, C.; Mandapati, S.; Van Hoosear, M.; Green, K. B.; Sonnentag, P.; Sharma, A. K.; Timmers, A.; Robinson, P. M.; Knop, D. R.; Hauswirth, W. W.; Chulay, J. D.; Shearman, M. S.; Ye, G. Toxicology and Pharmacology of an AAV Vector Expressing Codon-Optimized RPGR in RPGR-Deficient Rd9 Mice. Hum. Gene Then Clin. Dev. 2018, 29 (4), 188— 197. https: / / doi.Org / 10.1089 / humc.2018.168.

[0189] (13) Yin, X.; He, T.; Yang, S.; Cui, H.; Jiang, W. Efficacy and Safety of Antivascular Endothelial Growth Factor (Anti-VEGF) in Treating Neovascular Age-Related Macular Degeneration (AMD): A Systematic Review and Meta-Analysis. J. Immunol. Res. 2022, 2022, 1-11. https: / / doi.Org / 10.1155 / 2022 / 6004047.

[0190] (14) Gonzalez, V. H.; Berger, B.; Goldberg, R.; Gordon, C. M.; Khurana, R. N.; Angeles, R.; Shams, N. Safety and Tolerability of Intravitreal Carotuximab (DE-122) in Patients With Persistent Exudative Age-Related Macular Degeneration: A Phase I Study. Transl. Vis. Sci. Technol. 2021 , 10 (14), 27. https: / / doi.org / 10.1167 / tvst.10.14.27.

[0191] (15) Chong, V. Ranibizumab for the Treatment of Wet AMD: A Summary of Real-World Studies. Eye 2016, 30 (2), 270-286. https: / / d0i.0rg / l 0.1038 / eye.2015.217.

[0192] (16) Lee, A.; Shirley, M. Ranibizumab: A Review in Retinopathy of Prematurity. Pediatr. Drugs 2021 , 23 (1 ), 111-117. https: / / doi.Org / 10.1007 / s40272-020-00433-z.

[0193] (17) Nicolo, M.; Ferro Desideri, L.; Vagge, A.; Traverso, C. E. Faricimab: An Investigational Agent Targeting the Tie-2 / Angiopoietin Pathway and VEGF-A for the Treatment of Retinal Diseases. Expert Opin. Investig. Drugs 2021 , 30 (3), 193-200. https: / / doi.Org / 10.1080 / 13543784.2021 .1879791 .

[0194] (18) Changes in Retinal Neovascularization after Pegaptanib (Macugen) Therapy in Diabetic Individuals. Ophthalmology 2006, 113 (1 ), 23-28. https: / / d0i.0rg / l 0.1016 / j.ophtha.2005.10.012.

[0195] (19) Bbhni, S. C.; Bittner, M.; Howell, J. P.; Bachmann, L. M.; Faes, L.; Schmid, M. K. Comparison of Eylea® with Lucentis® as First-Line Therapy in Patients with Treatment-Naive Neovascular Age-Related Macular Degeneration in Real-Life Clinical Practice: Retrospective Case-Series Analysis. BMC Ophthalmol. 2015, 15 (1 ), 109. https: / / doi.Org / 10.1186 / S12886-015-0101 -4.

[0196] (20) Yang, L. P. H.; McKeage, K. Intravitreal Aflibercept (Eylea®): A Review of Its Use in Patients with Macular Oedema Secondary to Central Retinal Vein Occlusion. Drugs Aging 2014, 31 (5), 395-404. https: / / doi.Org / 10.1007 / S40266-014-0176-2.

[0197] (21 ) Crespo-Garcia, S.; Tsuruda, P. R.; Dejda, A.; Ryan, R. D.; Fournier, F.; Chaney, S. Y.; Pilon, F.; Dogan, T.; Cagnone, G.; Patel, P.; Buscarlet, M.; Dasgupta, S.; Girouard, G.; Rao, S. R.; Wilson, A. M.; O’Brien, R.;

[0198] Juneau, R.; Guber, V.; Dubrac, A.; Beausejour, C.; Armstrong, S.; Mallette, F. A.; Yohn, C. B.; Joyal, J.-S. ; Marquess, D.; Beltran, P. J.;

[0199] Sapieha, P. Pathological Angiogenesis in Retinopathy Engages Cellular Senescence and Is Amenable to Therapeutic Elimination via BCL-xL Inhibition. Cell Metab. 2021 , 33 (4), 818-832.e7. https: / / d0i.0rg / l 0.1016 / j.cmet.2O21 .01 .011 .

[0200] (22) da Cruz, L.; Dorn, J. D.; Humayun, M. S.; Dagnelie, G.; Handa, J.; Barale, P.-O.; Sahel, J. -A.; Stanga, P. E.; Hafezi, F.; Safran, A. B.;

[0201] Salzmann, J.; Santos, A.; Birch, D.; Spencer, R.; Cideciyan, A. V.; de Juan, E.; Duncan, J. L.; Eliott, D.; Fawzi, A.; Olmos de Koo, L. C.; Ho, A. C.; Brown, G.; Haller, J.; Regillo, C.; Del Priore, L. V.; Arditi, A.;

[0202] Greenberg, R. J. Five-Year Safety and Performance Results from the Argus II Retinal Prosthesis System Clinical Trial. Ophthalmology 2016, 123 (10), 2248-2254. https: / / doi.Org / 10.1016 / j.ophtha.2016.06.049.

[0203] (23) Muqit, M. M. K.; Velikay-Parel, M.; Weber, M.; Dupeyron, G.;

[0204] Audemard, D.; Corcostegui, B.; Sahel, J.; Le Mer, Y. Six-Month Safety and Efficacy of the Intelligent Retinal Implant System II Device in Retinitis Pigmentosa. Ophthalmology 2019, 126 (4), 637-639. https: / / d0i.0rg / l 0.1016 / j.ophtha.2018.11 .010.

[0205] (24) Palanker, D.; Le Mer, Y.; Mohand-Said, S.; Sahel, J. A. Simultaneous Perception of Prosthetic and Natural Vision in AMD Patients. Nat. Commun. 2022, 73 (1), 513. https: / / doi.org / 10.1038 / s41467- 022-28125-x.

[0206] (25) Park, J. H.; Shim, S.; Jeong, J.; Kim, S. J. A Multi-Photodiode Array-Based Retinal Implant IC with On / off Stimulation Strategy to Improve Spatial Resolution. JSTSJournal Semicond. Technol. Sci. 2017, 17 (1 ), 35-41 . https: / / doi.Org / 10.5573 / JSTS.2017.17.1 .035.

[0207] (26) Yanovitch, L.; Raz-Prag, D.; Hanein, Y. A New High-Resolution Three-Dimensional Retinal Implant: System Design and Preliminary Human Results; preprint; Bioengineering, 2022. https: / / doi.org / 10.1101 / 2022.09.14.507901.

[0208] (27) Francia, S.; Shmal, D.; Di Marco, S.; Chiaravalli, G.; Maya- Vetencourt, J. F.; Mantero, G.; Michetti, C.; Cupini, S.; Manfredi, G.; DiFrancesco, M. L.; Rocchi, A.; Perotto, S.; Attanasio, M.; Sacco, R.; Bisti, S.; Mete, M.; Pertile, G.; Lanzani, G.; Colombo, E.; Benfenati, F. Light- Induced Charge Generation in Polymeric Nanoparticles Restores Vision in Advanced-Stage Retinitis Pigmentosa Rats. Nat. Commun. 2022, 13 (1 ), 3677. https: / / d0i.0rg / l 0.1038 / S41467-022-31368-3.

[0209] (28) Klassen, H. Stem Cells in Clinical Trials for Treatment of Retinal Degeneration. Expert Opin. Biol. Ther. 2016, 16 (1 ), 7-14. https: / / doi.Org / 10.1517 / 14712598.2016.1093110.

[0210] (29) Guzman-Aranguez, A.; Loma, P.; Pintor, J. Small-Interfering RNAs (siRNAs) as a Promising Tool for Ocular Therapy: siRNA for Ocular Therapy. Br. J. Pharmacol. 2013, 170 (4), 730-747. https: / / d0i.0rg / l 0.1111 / bph.12330.

[0211] (30) Borkenstein, A. F.; Borkenstein, E.-M.; Augustin, A. J. Implantable Vision-Enhancing Devices and Postoperative Rehabilitation in Advanced Age-Related Macular Degeneration. Eye 2023, 37 (4), 597-606. https: / / d0i.0rg / l 0.1038 / S41433-022-02179-z.

[0212] (31 ) Markowitz, S. N.; Devenyi, R. G.; Munk, M. R.; Croissant, C. L.; Tedford, S. E.; Ruckert, R.; Walker, M. G.; Patino, B. E.; Chen, L.; Nido, M.; Tedford, C. E. A DOUBLE-MASKED, RANDOMIZED, SHAM- CONTROLLED, SINGLE-CENTER STUDY WITH PHOTOBIOMODULATION FOR THE TREATMENT OF DRY AGE- RELATED MACULAR DEGENERATION. Retina 2020, 40 (8), 1471-1482. https: / / doi.Org / 10.1097 / IAE.0000000000002632.

[0213] (32) Ghezzi, D.; Antognazza, M. R.; Dal Maschio, M.; Lanzarini, E.; Benfenati, F.; Lanzani, G. A Hybrid Bioorganic Interface for Neuronal Photoactivation. Nat. Commun. 2011 , 2, 166. https: / / d0i.0rg / l 0.1038 / ncomms1164.

[0214] (33) Benfenati, V.; Martino, N.; Antognazza, M. R.; Pistone, A.; Toffanin, S.; Ferroni, S.; Lanzani, G.; Muccini, M. Photostimulation of Whole-Cell Conductance in Primary Rat Neocortical Astrocytes Mediated by Organic Semiconducting Thin Films. Adv. Healthc. Mater. 2014, 3 (3), 392-399. https: / / d0i.0rg / l 0.1002 / adhm.201300179.

[0215] (34) Lodola, F.; Martino, N.; Tullii, G.; Lanzani, G.; Antognazza, M. R. Conjugated Polymers Mediate Effective Activation of the Mammalian Ion Channel Transient Receptor Potential Vanilloid 1 . Sci. Rep. 2017, 7 (1 ). https: / / d0i.0rg / l 0.1038 / S41598-017-08541 -6.

[0216] (35) Ghezzi, D.; Antognazza, M. R.; Maccarone, R.; Bellani, S.; Lanzarini, E.; Martino, N.; Mete, M.; Pertile, G.; Bisti, S.; Lanzani, G.; Benfenati, F. A Polymer Optoelectronic Interface Restores Light Sensitivity in Blind Rat Retinas. Nat. Photonics 2013, 7 (5), 400-406. https: / / d0i.0rg / l 0.1038 / nphoton.2013.34.

[0217] (36) Feyen, P.; Colombo, E.; Endeman, D.; Nova, M.; Laudato, L.; Martino, N.; Antognazza, M. R.; Lanzani, G.; Benfenati, F.; Ghezzi, D. Light-Evoked Hyperpolarization and Silencing of Neurons by Conjugated Polymers. Sci. Rep. 2016, 6 (1 ). https: / / doi.org / 10.1038 / srep22718.

[0218] (37) Vagni, P.; Airaghi Leccardi, M. J. L; Vila, C.-H.; Zollinger, E. G.; Sherafatipour, G.; Wolfensberger, T. J.; Ghezzi, D. POLYRETINA Restores Light Responses in Vivo in Blind Gottingen Minipigs. Nat. Commun. 2022, 73 (1 ), 3678. https: / / doi.org / 10.1038 / s41467-022-31180- z. (38) Maya-Vetencourt, J. F.; Ghezzi, D.; Antognazza, M. R.; Colombo,

[0219] E.; Mete, M.; Feyen, P.; Desii, A.; Buschiazzo, A.; Di Paolo, M.; Di Marco, S.; Ticconi, F.; Emionite, L.; Shmal, D.; Marini, C.; Donelli, I.; Freddi, G.; Maccarone, R.; Bisti, S.; Sambuceti, G.; Pertile, G.; Lanzani, G.; Benfenati,

[0220] F. A Fully Organic Retinal Prosthesis Restores Vision in a Rat Model of Degenerative Blindness. Nat. Mater. 2017. https: / / doi.Org / 10.1038 / nmat4874.

[0221] (39) Maya-Vetencourt, J. F.; Manfredi, G.; Mete, M.; Colombo, E.; Bramini, M.; Di Marco, S.; Shmal, D.; Mantero, G.; Dipalo, M.; Rocchi, A.; DiFrancesco, M. L.; Papaleo, E. D.; Russo, A.; Barsotti, J.; Eleftheriou, C.; Di Maria, F.; Cossu, V.; Piazza, F.; Emionite, L.; Ticconi, F.; Marini, C.; Sambuceti, G.; Pertile, G.; Lanzani, G.; Benfenati, F. Subretinally Injected Semiconducting Polymer Nanoparticles Rescue Vision in a Rat Model of Retinal Dystrophy. Nat. Nanotechnol. 2020. https: / / d0i.0rg / l 0.1038 / S41565-020-0696-3.

[0222] (40) Manfredi, G.; Colombo, E.; Barsotti, J.; Benfenati, F.; Lanzani, G. Photochemistry of Organic Retinal Prostheses. Annu. Rev. Phys. Chem. 2019, 70 (1 ), 99-121. https: / / doi.org / 10.1146 / annurev-physchem-042018- 052445.

[0223] (41 ) Chiaravalli, G.; Manfredi, G.; Sacco, R.; Lanzani, G. Photoelectrochemistry and Drift-Diffusion Simulations in a Polythiophene Film Interfaced with an Electrolyte. ACS Appl. Mater. Interfaces 2021 , 13 (30), 36595-36604. https: / / doi.org / 10.1021 / acsami.1 c10158.

[0224] (42) Palanker, D.; Glowacki, E. D.; Ghezzi, D. Questions about the Role of P3HT Nanoparticles in Retinal Stimulation. Nat. Nanotechnol. 2021 , 16 (12), 1330-1332. https: / / doi.org / 10.1038 / s41565-021 -01044-6.

[0225] (43) Willermain, F.; Scifo, L.; Weber, C.; Caspers, L.; Perret, J.; Delporte, C. Potential Interplay between Hyperosmolarity and Inflammation on Retinal Pigmented Epithelium in Pathogenesis of Diabetic Retinopathy. Int. J. Mol. Sci. 2018, 19 (4), 1056. https: / / d0i.0rg / l 0.3390 / ijms19041056. (44) Hancock, S. E.; Wan, C.-R.; Fisher, N. E.; Andino, R. V.; Ciulla, T. A. Biomechanics of Suprachoroidal Drug Delivery: From Benchtop to Clinical Investigation in Ocular Therapies. Expert Opin. Drug Deliv. 2021 , 18 (6), 777-788. https: / / doi.org / 10.1080 / 17425247.2021.1867532. (45) Zucchetti, E.; Zangoli, M.; Bargigia, I.; Bossio, C.; Di Maria, F.; Barbarella, G.; D’Andrea, C.; Lanzani, G.; Antognazza, M. R. Poly(3- Hexylthiophene) Nanoparticles for Biophotonics: Study of the Mutual Interaction with Living Cells. J Mater Chem B 2017, 5 (3), 565-574. https: / / doi.Org / 10.1039 / C6TB02047J.

Claims

CLAIMS1. A composition comprising a suspension of poly(3-hexylthiophene) (P3HT) nanoparticles and / or nanoparticles with core@shell structure having a core comprising P3HT and a shell comprising oxidized poly(3- hexylthiophene) (P3HT-PTDO), in an aqueous solution, wherein the aqueous solution comprises at least sodium ions and chloride ions together with at least one stabilizing agent selected from: a non-ionic surfactant and / or a water-soluble polymer having high intrinsic viscosity, wherein the non-ionic surfactant is selected from: poloxamer P188, Tween 80, Kollipor P407, Kollipor HS 15, Brij35, Cremophor RH40, Tween 20, Tween 60, Oramix CG110, Oramix NS10 and combination thereof.

2. The composition according to claim 1 , wherein the concentration of nanoparticles is from 0.1 to 0.8 mg / ml, preferably from 0.1 to 0.6 mg / ml.

3. The composition according to claim 1 or 2, wherein the sodium ions are present in a concentration of 0.1 - 0.4 mol / L4. The composition according any one of the preceding claims, wherein the chloride ions are present in a concentration of 0.1 - 0.4 mol / L5. The composition according to any one of the preceding claims, wherein the water-soluble polymer is selected from hyaluronic acid or salts thereof, polyvinyl alcohol (PVA) and / or polyvinyl pyrrolidone (PVP).

6. The composition according to any one of the preceding claims, further comprising at least one of: magnesium ions, preferably in a concentration of 0.0005 mol / L - 0.005 mol / L, calcium ions preferably in a concentration of 0.0005 mol / L - 0.007 mol / L, potassium ions preferably in a concentration of 0.0005 mol / L - 0.03 mol / L, and combination thereof.

7. The composition according to any one of the preceding claims, having a pH between 6 and 8, preferably between 6.8 and 7.4.

8. The composition according to any one of the preceding claims, having an osmolarity between 200-400 mOsm / L, preferably between 280-320 mOsm / L.

9. A kit comprising a part A and a part B, wherein part A comprises an aqueous suspension of poly(3-hexylthiophene) (P3HT) nanoparticles and / or nanoparticles with core@shell structure having a core comprising P3HT and a shell comprising oxidized poly(3-hexylthiophene) (P3HT- PTDO), and part B comprises an aqueous solution comprising at least sodium ions and chloride ions together with at least one stabilizing agent selected from: a non-ionic surfactant, a water-soluble polymer and a combination thereof.

10. The kit according to claim 9, wherein the aqueous suspension of part A comprises from 0.2 to 1 .6 mg / ml of nanoparticles, preferably from 0.2 to 1 .2 mg / ml of nanoparticles.

11. An aqueous solution comprising at least sodium ions, preferably present in a concentration of 0.2 - 0.8 mol / l, and chloride ions, preferably present in a concentration of 0.2 - 0.8 mol / l, wherein the composition further comprises at least one stabilizing agent selected from: a non-ionic surfactant and / or a water-soluble polymer having high intrinsic viscosity, wherein the non-ionic surfactant is selected from: poloxamer P188, Tween 80, Kollipor P407, Kollipor HS 15, Brij35, Cremophor RH40, Tween 20, Tween 60, Oramix CG110, Oramix NS10 and combination thereof.

12. The aqueous solution according to claim 11 , further comprising at leastone of: magnesium ions, preferably in a concentration of 0.001 mol / L - 0.01 mol / L, calcium ions preferably in a concentration of 0.001 mol / L - 0.014 mol / L, potassium ions preferably in a concentration of 0.001 mol / L - 0.06 mol / L, carbonate and / or citrate and / or acetate ions, preferably in a concentration of 0.02 mol / L - 0.4 mol / L, 0.002 mol / L - 0.014 mol / L, 0.02 mol / L - 0.4 mol / L, respectively, and combination thereof.

13. A method for preparing the composition according to claim 1 , comprising a step of mixing an aqueous suspension of P3HT and / or P3HT-PTDO nanoparticles, preferably comprising 0.2 to 1.6 mg / ml of nanoparticles, more preferably 0.2 to 1 .2 mg / ml of nanoparticles, with an aqueous solution comprising at least sodium ions and chloride ions together with at least one stabilizing agent selected from: a non-ionic surfactant and / or a water-soluble polymer having high intrinsic viscosity, wherein the non-ionic surfactant is selected from: poloxamer P188, Tween 80, Kollipor P407, Kollipor HS 15, Brij35, Cremophor RH40, Tween 20, Tween 60, Oramix CG110, Oramix NS10 and combination thereof.

14. The composition according to any one of the claims from 1 to 8 or the kit of claim 9 or 10, for use as medicament, preferably for treating a visual deficit.

15. The composition or the kit for use according to claim 14, to recover sensitivity and / or visual performances of a malfunctioning eye, for treating blindness, preferably secondary to the degeneration and / or malfunction of eye photoreceptors, and / or to substitute degenerated and / or impaired photoreceptors of an eye.

16. The composition or the kit for use according to claim 14 in the treatment of retinal dystrophies selected from: Retinitis Pigmentosa (RP), Leber Congenital Amaurosis (LCA), Achromatopsia and Cone RodDystrophy; and / or retinal neurodegenerative diseases selected from age- related macular degeneration (AMD), diabetic retinopathy and glaucoma.

17. The composition or the kit for use according to any one of the claims from 14 to 16, wherein the composition is injected inside a quadrant of the retina, wherein the quadrant is affected by atrophy of photoreceptors.

18. Use of a high intrinsic viscosity water soluble polymer and / or a nonionic surfactant to stabilize a suspension of poly(3-hexylthiophene) (P3HT) and / or P3HT-PTDO nanoparticles in an aqueous solution comprising at least sodium ions and chloride ions, wherein the non-ionic surfactant is selected from poloxamer P188, Tween 80, Kollipor P407, Kollipor HS 15, Brij35, Cremophor RH40, Tween 20, Tween 60, Oramix CG110 and Oramix NS10.

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