Formulation based on quinoline derivatives for the targeted treatment of Alzheimer's disease

Abstract

A pharmaceutical composition for the targeted treatment of Alzheimer's disease, comprising: a. a quinoline derivative selected from the group consisting of 2-methylquinoline, 6-chloroquinoline and 3-hydroxyquinoline, present in an amount in the range of 5 to 30 wt% of the total composition; b. Lipid nanoparticles consisting of phospholipids and cholesterol, in an amount of 30 to 40 percent by weight of the total composition; c. Polyethylene glycol (PEG), present in an amount of 5 to 10 percent by weight of the total composition; d. Sodium chloride, present in an amount of 0.5 to 1% by weight of the total composition; e. Sodium phosphate, present in an amount of 0.2 to 0.5 percent by weight of the total composition; and f. a pharmaceutically acceptable carrier or excipient.

Description

Field of the invention:

[0001] The present invention relates to a pharmaceutical composition containing quinoline derivatives intended for the targeted treatment of Alzheimer's disease. More specifically, the invention relates to the formulation of quinoline derivatives in combination with suitable excipients to improve their bioavailability and selective action in the brain. These formulations are intended to offer a novel approach to the treatment of Alzheimer's disease by targeting underlying pathological mechanisms such as amyloid plaque formation, tau protein aggregation, and neuroinflammation. Background of the invention:

[0002] Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and memory loss, for which there is no definitive cure. The disease is characterized by the accumulation of amyloid plaques and tau fibrils in the brain, as well as neuronal loss and synaptic dysfunction. Current therapeutic strategies primarily aim to alleviate symptoms or slow disease progression, but these treatments often fail to address the underlying pathophysiology. Quinoline derivatives have shown potential in preclinical studies to modulate amyloid beta and tau pathology and reduce neuroinflammation, making them promising candidates for targeted therapy in Alzheimer's disease. However, the effective delivery of these compounds to the brain while crossing the blood-brain barrier remains a critical challenge.

[0003] Alzheimer's disease (AD) is a progressive neurodegenerative disorder and one of the most common causes of dementia in older people. It is characterized by a gradual decline in cognitive functions, including memory, attention, language, and reasoning. The pathophysiology of Alzheimer's disease is multifactorial. The most prominent features include the accumulation of amyloid beta plaques, tau fibrils, synaptic dysfunction, neuroinflammation, and nerve cell death. Despite decades of research, there are still no effective treatments for Alzheimer's disease. Current therapies offer only limited symptom relief rather than halting or reversing the underlying disease processes.The increasing prevalence of Alzheimer's disease worldwide due to an aging population underscores the urgent need for more effective treatments that target the underlying mechanisms of the disease.

[0004] The most prevalent pathological hallmark of Alzheimer's disease is the accumulation of amyloid-beta (Aß) plaques. These plaques result from the abnormal cleavage of the amyloid precursor protein (APP) and the aggregation of Aß peptides, forming insoluble fibrils. Amyloid plaques disrupt neuronal communication, activate neuroinflammatory pathways, and trigger oxidative stress, all of which contribute to cognitive decline. In addition to amyloid plaques, another important pathological feature is the formation of neurofibrillary tangles composed of hyperphosphorylated tau protein. Tau is a microtubule-associated protein that normally stabilizes microtubules in neurons. In Alzheimer's disease, tau undergoes abnormal phosphorylation, leading to its detachment from microtubules and the formation of tangles that disrupt axonal transport and impair synaptic function.

[0005] Current pharmacological therapies for Alzheimer's disease primarily include acetylcholinesterase inhibitors and glutamate antagonists. Acetylcholinesterase inhibitors such as donepezil, rivastigmine, and galantamine work by increasing levels of acetylcholine, a neurotransmitter involved in memory and learning. However, their effectiveness is limited because they only provide temporary symptom relief without addressing the underlying disease mechanisms. Glutamate antagonists such as memantine regulate glutamate activity and reduce excitotoxicity, but like acetylcholinesterase inhibitors, they do not affect disease progression. Recently, monoclonal antibodies such as aducanumab, which target amyloid plaques, have been approved by regulatory authorities.These drugs aim to remove amyloid deposits from the brain, but clinical trials have shown mixed results: Some patients experienced limited cognitive improvement, while others experienced adverse side effects such as brain swelling and microbleeds. The lack of significant efficacy and the high cost of these treatments have led to a reconsideration of their widespread use in clinical practice.

[0006] One of the biggest challenges in developing effective treatments for Alzheimer's disease is delivering therapeutics to the brain. The blood-brain barrier (BBB), a selective barrier that protects the brain from harmful substances, simultaneously limits the ability of many drugs to reach the central nervous system (CNS) in sufficient concentrations. This challenge is particularly problematic for small-molecule drugs, which must cross the BBB to exert their therapeutic effects. Numerous strategies have been explored to improve drug delivery across the BBB, including the use of nanoparticles, liposomes, and prodrugs.Nanoparticles, especially lipid-based nanoparticles (LNPs), have shown promise in drug delivery for central nervous system diseases due to their ability to encapsulate both hydrophobic and hydrophilic compounds, protect drugs from degradation, and facilitate transport across the BBB through receptor-mediated endocytosis.

[0007] Quinoline derivatives have gained attention in recent years as potential therapeutics for Alzheimer's disease due to their ability to modulate amyloid beta aggregation, inhibit tau phosphorylation, and reduce neuroinflammation. Quinoline is a bicyclic heterocyclic compound that has been shown to possess a range of pharmacological properties, including anti-inflammatory, antioxidant, and neuroprotective effects. Several quinoline derivatives, such as 2-methylquinoline, 6-chloroquinoline, and 3-hydroxyquinoline, have demonstrated promising activity in preclinical models of Alzheimer's disease, demonstrating the potential to reduce amyloid burden, prevent tau toxicity, and protect neurons from oxidative damage. However, a major limitation of quinoline derivatives is their poor solubility and bioavailability, which significantly compromises their efficacy upon systemic administration.Furthermore, these compounds often have low brain penetration due to the restrictive nature of the blood-brain barrier, making it difficult to achieve therapeutic concentrations in the central nervous system.

[0008] Despite the promising results of quinoline derivatives in preclinical studies, there is a lack of effective formulations that can overcome these barriers and improve the bioavailability and targeted delivery of these compounds to the brain. To achieve a meaningful therapeutic effect, quinoline derivatives must be delivered in a manner that ensures high concentrations in the brain while minimizing systemic side effects. Therefore, there is an urgent need for a new formulation that not only improves the solubility, stability, and brain penetration of quinoline derivatives, but also ensures their targeted delivery to the brain areas affected by Alzheimer's disease. Summary of the invention:

[0009] The present invention provides a novel formulation of quinoline derivatives optimized for the targeted treatment of Alzheimer's disease. The formulation contains one or more quinoline derivatives along with pharmacologically acceptable excipients that promote targeted delivery to the brain. By incorporating these compounds into a specific dosage form, bioavailability and therapeutic efficacy in the treatment of Alzheimer's disease are significantly improved.

[0010] The quinoline derivatives of this invention may include compounds such as 2-methylquinoline, 6-chloroquinoline, or 3-hydroxyquinoline, each of which plays a role in the inhibition of amyloid aggregation, tau phosphorylation, and modulation of inflammatory pathways. These compounds may be used in their pure form or as part of a prodrug that is enzymatically converted to the active quinoline derivative in the brain.

[0011] The primary objective of the present invention is to provide a novel pharmaceutical formulation containing quinoline derivatives specifically designed for the targeted treatment of Alzheimer's disease. This formulation aims to overcome the limitations of poor solubility, bioavailability, and brain penetration associated with quinoline derivatives, thus improving their efficacy in the treatment of Alzheimer's disease. By utilizing advanced drug delivery systems such as lipid nanoparticles (LNPs), the formulation ensures improved transport across the blood-brain barrier (BBB) ​​and localized delivery of the active quinoline derivative to the brain.

[0012] Another aim of the invention is to provide a formulation that can effectively modulate the key pathological processes of Alzheimer's disease, including amyloid beta aggregation, tau phosphorylation, and neuroinflammation. The quinoline derivatives contained in the formulation are selected for their ability to inhibit the formation of amyloid plaques, prevent tau fibrils, and reduce neuroinflammatory responses, thereby addressing the core mechanisms of Alzheimer's disease progression.

[0013] Another objective of the invention is to provide a formulation that is both safe and effective, with minimal side effects. The use of lipid nanoparticles as carriers not only improves the solubility and bioavailability of quinoline derivatives but also offers the possibility of sustained release of the drug, thereby reducing the need for frequent dosing and minimizing the risk of systemic toxicity. The inclusion of stabilizers and excipients ensures the stability of the formulation and makes it suitable for long-term use in patients with Alzheimer's disease.

[0014] Furthermore, the invention aims to provide a formulation that can be administered in various ways, including oral and injectable forms, to offer flexible treatment options. By optimizing the pharmacokinetics and pharmacodynamics of the quinoline derivatives, the formulation is intended to improve patient compliance and achieve better outcomes in the treatment of Alzheimer's disease.

[0015] In summary, the goal of this invention is to develop a novel brain-targeted formulation of quinoline derivatives that effectively addresses the underlying pathophysiology of Alzheimer's disease. Through improved drug delivery systems, the invention aims to provide a safe, effective, and long-term treatment option that can potentially slow or halt the progression of this devastating neurodegenerative disease. SHORT DESCRIPTION OF THE FIGURE

[0016] These and other features, aspects, and advantages of the present invention will become more readily understood when the following detailed description is read in conjunction with the accompanying drawings, in which like characters represent like parts throughout. Fig. Figure 1 shows a data table indicating the synergistic effect of the quinoline derivative-based formulation in the treatment of Alzheimer's disease.

[0017] Furthermore, those skilled in the art will appreciate that elements in the drawing are illustrated for convenience and may not necessarily be drawn to scale. Furthermore, with respect to the construction of the device, one or more components of the device may be represented in the drawing by conventional symbols, and the drawing may show only the specific details relevant to understanding the embodiments of the present disclosure in order not to clutter the drawing with details that would be readily apparent to those skilled in the art who would benefit from the description herein. Detailed description of the invention:

[0018] To facilitate an understanding of the principles of the invention, reference will now be made to the embodiment illustrated in the drawings and described in specific language. It is to be understood, however, that no limitation on the scope of the invention is intended thereby, since such changes and further modifications of the illustrated system, and such further applications of the principles of the invention as illustrated therein, are contemplated as would normally occur to one skilled in the art to which the invention pertains.

[0019] It will be understood by one skilled in the art that the foregoing general description and the following detailed description are exemplary and explanatory of the invention and are not intended to be limiting thereof.

[0020] References in this specification to "one aspect," "another aspect," or similar language mean that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present disclosure. Therefore, occurrences of the phrase "in one embodiment," "in another embodiment," and similar language throughout this specification may or may not all refer to the same embodiment.

[0021] The terms "comprises," "comprising," or other variations thereof are intended to cover non-exclusive inclusion, such that a process comprising a list of steps not only includes those steps, but may also include other steps not expressly listed or inherent in such processes. Likewise, one or more devices or subsystems or elements or structures or components preceded by "comprises...a" does not preclude, without further limitation, the existence of other devices or other subsystems or other elements or other structures or other components or additional devices or additional subsystems or additional elements or additional structures or additional components.

[0022] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Embodiments of the present disclosure will be described in detail below with reference to the accompanying drawings.

[0023] In one embodiment, the present invention provides the composition for a pharmaceutical composition for the targeted treatment of Alzheimer's disease, comprising: a. A quinoline derivative selected from the group consisting of 2-methylquinoline, 6-chloroquinoline, and 3-hydroxyquinoline, present in an amount ranging from 5% to 30% by weight of the total composition; b. Lipid nanoparticles comprising phospholipids and cholesterol, present in an amount ranging from 30% to 40% by weight of the total composition; c. Polyethylene glycol (PEG), present in an amount ranging from 5% to 10% by weight of the total composition; d. Sodium chloride, present in an amount ranging from 0.5% to 1% by weight of the total composition; e. Sodium phosphate, present in an amount ranging from 0.2% to 0.5% by weight of the total composition; and f. A pharmaceutically acceptable carrier or excipient.

[0024] In one embodiment, the quinoline derivative is 2-methylquinoline, which is present at a concentration of 15% by weight of the total composition.

[0025] In one embodiment, the quinoline derivative is 6-chloroquinoline, which is present at a concentration of 20% by weight of the total composition.

[0026] In one embodiment, the lipid nanoparticles comprise phospholipids selected from the group consisting of phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine, and cholesterol in a ratio of approximately 4:1 to 7:1.

[0027] In one embodiment, the polyethylene glycol (PEG) is PEG-2000 or PEG-5000 and is present at a concentration of 7% by weight of the total composition.

[0028] In one embodiment, the sodium chloride is present at a concentration of 0.7% by weight of the total composition.

[0029] In one embodiment, the sodium phosphate is present at a concentration of 0.3% by weight of the total composition.

[0030] In one embodiment, the pharmaceutically acceptable carrier or excipient is selected from the group consisting of water, saline, and phosphate buffered saline.

[0031] Fig. Figure 1 illustrates the synergistic effect and technical efficacy of the quinoline derivative-based formulation in the treatment of Alzheimer's disease.

[0032] The data presented in the table demonstrate the improved therapeutic efficacy of the LNP-encapsulated quinoline derivative formulation compared to free quinoline in the treatment of Alzheimer's disease. Regarding the reduction of amyloid plaque burden, the LNP-encapsulated quinoline derivative achieved a 45 percent reduction in brain amyloid beta plaque burden, which is significantly higher than the 25 percent reduction observed in the free quinoline group. This suggests that the lipid nanoparticle formulation significantly enhances the ability of the quinoline derivative to target and reduce amyloid plaques, a key pathological feature of Alzheimer's disease.

[0033] Likewise, when assessing tau phosphorylation at critical epitopes (Ser396 and Thr231), the LNP formulation demonstrated a 38% reduction in tau phosphorylation, exceeding the 20% reduction observed with free quinoline. This suggests that the LNP-encapsulated formulation can more effectively modulate tau pathology, another central hallmark of Alzheimer's disease. The anti-inflammatory effects of the formulation were also pronounced: The LNP-encapsulated quinoline reduced the pro-inflammatory cytokines TNF-α and IL-1β by 50%, compared to only a 20% reduction in free quinoline-treated animals. This significant reduction in inflammatory markers further underscores the increased therapeutic potential of the LNP formulation in treating neuroinflammation, a crucial factor in the pathophysiology of Alzheimer's disease.

[0034] Brain penetration data also underscore the superiority of the LNP formulation. The concentration of quinoline in the brain tissue of animals treated with the LNP-encapsulated formulation was 175 ng / g, almost three and a half times higher than the 50 ng / g observed in the brains of animals treated with free quinoline. This improved brain penetration is crucial for targeting the central nervous system and addressing the neurodegenerative aspects of Alzheimer's disease.

[0035] Finally, improvements in cognitive function, measured using the Morris water maze test, demonstrate the efficacy of the LNP-encapsulated quinoline formulation. LNP-treated mice showed a 40 percent improvement in escape latency, indicating better spatial learning and memory, compared to a 20 percent improvement in the free quinoline-treated group. This cognitive benefit strongly correlates with the reduction of amyloid plaques, tau phosphorylation, and neuroinflammation, suggesting that the enhanced therapeutic effect of the LNP-encapsulated formulation leads to better cognitive outcomes in Alzheimer's disease.

[0036] Overall, the data confirm that the LNP-encapsulated quinoline derivative formulation offers superior therapeutic efficacy compared to free quinoline in reducing amyloid plaques, modulating tau pathology, reducing neuroinflammation, improving brain penetration, and improving cognitive function. These results demonstrate the synergistic effect of the formulation and its potential as a promising treatment for Alzheimer's disease.

[0037] The quinoline derivatives are used in an amount of 5 to 30% by weight of the total composition, depending on the specific compound used and its efficacy. In one preferred embodiment, 2-methylquinoline is present at a concentration of 15%, while in another, 6-chloroquinoline is used at a concentration of 20%. These concentrations are selected based on in vitro and in vivo studies demonstrating optimal pharmacological activity at these concentrations, particularly with regard to amyloid beta modulation and tau protein inhibition.

[0038] In addition to the quinoline derivative, the formulation contains a carrier or excipient to assist in the solubilization and delivery of the active ingredient across the blood-brain barrier. Lipid nanoparticles (LNPs) are preferred because they provide effective encapsulation of the quinoline derivative, thus ensuring improved transport across the BBB. These lipid nanoparticles are used in a concentration range of 30% to 40%, with 35% LNPs being particularly effective for sustained release of the active ingredient. Furthermore, the inclusion of polyethylene glycol (PEG) in the formulation (5% to 10%) provides improved stability and a longer half-life of the drug, enabling a more sustained therapeutic effect.

[0039] Another important component of the formulation is a stabilizer such as sodium chloride (0.5% to 1%), which helps maintain the isotonicity of the formulation and thus ensures patient safety during administration. The composition may also contain a suitable buffering agent such as sodium phosphate at a concentration of approximately 0.2% to 0.5% to maintain a suitable pH (between 4.5 and 7.0), ensuring the stability of the quinoline derivatives during storage and administration.

[0040] To improve patient compliance, the formulation can be prepared as oral tablets, capsules, or an injectable solution. The intended dosage ranges from 10 mg to 100 mg per day, depending on the severity of the disease and individual patient response. Dosage is typically administered once or twice daily, with variations possible depending on clinical need.

[0041] The pharmaceutical composition of the invention is intended for administration in various forms, for example, as oral tablets, capsules, or injections. For oral administration, one tablet or capsule may contain 20 to 50 mg of quinoline derivative (e.g., 2-methylquinoline) combined with 35% lipid nanoparticles, 5% polyethylene glycol, 0.5% sodium chloride, and 0.3% sodium phosphate. The excipients and active ingredients are carefully mixed and compressed to ensure uniform distribution and stability throughout the product's shelf life.

[0042] For parenteral administration, a solution can be prepared containing 10 to 30 mg of the active quinoline derivative dissolved in a suitable solvent such as saline or phosphate-buffered saline (PBS), with the appropriate lipid carrier system to facilitate delivery to the central nervous system. Injectable forms are particularly useful in acute or advanced stages of Alzheimer's disease when rapid delivery to the brain is required.

[0043] The quinoline derivative-based formulation of this invention is administered to individuals diagnosed with Alzheimer's disease to slow the progression of cognitive decline. Treatment involves regular administration of the formulation, either orally or by injection, as prescribed by a physician. The formulation works by crossing the blood-brain barrier and interacting with amyloid plaques and tau fibrils, inhibiting their formation or promoting their clearance. Furthermore, the anti-inflammatory effects of the quinoline derivatives help reduce neuronal damage and protect brain function over time.

[0044] The formulation offers several advantages over existing treatments for Alzheimer's disease. First, the targeted delivery of quinoline derivatives through lipid nanoparticles significantly improves bioavailability and therapeutic efficacy in the brain, offering the potential for improved outcomes in cognitive function and disease progression. Furthermore, the use of lipid nanoparticles and polyethylene glycol ensures prolonged stability and reduces the risk of side effects, making the treatment safer and more effective in the long term.

[0045] Furthermore, the invention's ability to target multiple pathophysiological processes—amyloid beta deposition, tau aggregation, and neuroinflammation—enables a multifaceted approach to treating Alzheimer's disease, distinguishing it from existing therapies that typically focus on only one of these mechanisms.

[0046] To demonstrate the synergistic effect and technical efficacy of the quinoline derivative-based formulation for the targeted treatment of Alzheimer's disease, a series of preclinical studies were conducted to assess the compound's ability to modulate key pathological features of the disease, such as amyloid-beta aggregation, tau phosphorylation, and neuroinflammation. These studies were designed to demonstrate the improved efficacy of the formulation compared to non-encapsulated quinoline derivatives, with a focus on the role of lipid nanoparticle (LNP) encapsulation in improving drug delivery and brain penetration.

[0047] In the first experiment, a murine Alzheimer's disease model (APP / PS1 transgenic mice) was used to investigate the effect of a quinoline-derivative-based formulation on amyloid-beta plaque burden. The mice were treated with 15% 2-methylquinoline encapsulated in lipid nanoparticles (LNP formulation) at a dose of 20 mg / kg body weight for 4 weeks. Control groups received either a placebo formulation (vehicle) or free 2-methylquinoline (without LNP encapsulation) at the same dose. After 4 weeks of treatment, amyloid-beta plaque burden in the hippocampus and cortex was measured using immunohistochemical staining for amyloid-beta. The LNP-encapsulated quinoline formulation resulted in a 45% reduction in amyloid plaques compared to the placebo group (p < 0.05), while treatment with free quinoline showed a more modest reduction of 25% (p < 0.05).These results demonstrate that the LNP-encapsulated quinoline derivative formulation significantly improves amyloid beta clearance, likely due to improved brain delivery and prolonged drug retention at the target site.

[0048] Further studies were conducted to investigate the effect of the formulation on tau pathology, a key feature of Alzheimer's disease. In this experiment, tau phosphorylation was assessed in the same animal model using Western blot analysis of tau phosphorylation at key epitopes (Ser396 and Thr231). Mice treated with the LNP-encapsulated quinoline formulation showed a 38 percent reduction in tau phosphorylation compared to the placebo group (p < 0.05). In contrast, the free quinoline derivative showed only a 20 percent reduction in tau phosphorylation, suggesting that encapsulation of quinoline in lipid nanoparticles significantly improves its ability to modulate tau pathology.

[0049] To assess the anti-inflammatory effect of the quinoline derivative-based formulation, brain levels of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, were measured using an enzyme-linked immunosorbent assay (ELISA). Mice treated with the LNP-encapsulated quinoline formulation exhibited a 50% reduction in brain TNF-α and IL-1β levels compared to the placebo group (p < 0.05), indicating a potent anti-inflammatory response. The free quinoline derivative showed a slight reduction of these cytokines by approximately 20%, highlighting the importance of the LNP formulation in enhancing the anti-inflammatory properties of quinoline derivatives. Furthermore, there was no significant change in cytokine levels in the placebo group, confirming that the observed effects were specifically due to quinoline treatment.

[0050] The brain penetration and bioavailability of the quinoline derivatives were also assessed in vivo using a pharmacokinetic study. Quinoline levels in plasma and brain tissue were measured after a single dose of the LNP-encapsulated formulation (20 mg / kg body weight) and free quinoline (20 mg / kg). The results showed that the LNP-encapsulated quinoline derivative achieved significantly higher brain concentrations than free quinoline. Specifically, brain quinoline concentrations in the LNP formulation group were approximately 3.5 times higher than in the free quinoline group four hours after administration (p < 0.01). These data clearly demonstrate that the lipid nanoparticle formulation significantly improves brain penetration and promotes the delivery of the quinoline derivatives to the central nervous system.

[0051] Behavioral tests were also conducted to evaluate cognitive improvements resulting from treatment. In a Morris water maze test, which measures spatial learning and memory, mice treated with the LNP-encapsulated quinoline formulation showed a 40 percent improvement in escape delay and a 30 percent improvement in path length compared to the placebo group (p < 0.05). Mice treated with free quinoline showed a 20 percent improvement in escape delay but no significant improvement in path length, highlighting the enhanced cognitive benefits of the LNP formulation.

[0052] Taken together, these experimental studies demonstrate that the quinoline derivative-based formulation, especially when encapsulated in lipid nanoparticles, exhibits synergistic effects in treating multiple pathological aspects of Alzheimer's disease. The LNP formulation not only improves the delivery and bioavailability of quinoline derivatives but also significantly enhances their efficacy in reducing amyloid-beta plaque burden, modulating tau phosphorylation, and reducing neuroinflammation. The pharmacokinetic data further support the technical efficacy of the LNP formulation in enhancing brain penetration and achieving therapeutic concentrations in the central nervous system. These results provide strong preclinical evidence that the quinoline derivative-based formulation holds promise as a novel treatment strategy for Alzheimer's disease.

[0053] The drawings and the foregoing description provide examples of embodiments. Those skilled in the art will recognize that one or more of the described elements may well be combined into a single functional element. Alternatively, certain elements may be separated into multiple functional elements. Elements from one embodiment may be added to another embodiment. For example, orders of the processes described herein may be changed and are not limited to the manner described herein. Furthermore, the actions of any flowchart need not be implemented in the order shown; nor do all actions necessarily need to be performed. Also, those actions that are not dependent on other actions may be performed in parallel with the other actions. The scope of the embodiments is in no way limited by these specific examples.Numerous variations, whether explicitly stated in the specification or not, such as differences in structure, dimensions, and material use, are possible. The scope of the embodiments is at least as broad as indicated in the following claims.

[0054] Advantages, other benefits, and solutions to problems have been described above with reference to specific embodiments. However, the advantages, benefits, solutions to problems, and any components that may cause an advantage or solution to occur or become more apparent are not to be construed as a critical, required, or essential feature or component of any or all of the claims.

Claims

[1] A pharmaceutical composition for the targeted treatment of Alzheimer’s disease, comprising: a. a quinoline derivative selected from the group consisting of 2-methylquinoline, 6-chloroquinoline and 3-hydroxyquinoline, present in an amount ranging from 5 to 30% by weight of the total composition; b. Lipid nanoparticles consisting of phospholipids and cholesterol in an amount of 30 to 40% by weight of the total composition; c. Polyethylene glycol (PEG), present in an amount of 5 to 10% by weight of the total composition; d. Sodium chloride, present in an amount of 0.5 to 1% by weight of the total composition; e. Sodium phosphate, present in an amount of 0.2 to 0.5% by weight of the total composition; and f. a pharmaceutically acceptable carrier or excipient. [2] A composition according to claim 1, wherein the quinoline derivative is 2-methylquinoline and is present in a concentration of 15% by weight of the total composition. [3] Composition according to claim 1, wherein the quinoline derivative is 6-chloroquinoline and is present in a concentration of 20% by weight of the total composition. [4] The composition of claim 1, wherein the lipid nanoparticles comprise phospholipids selected from the group consisting of phosphatidylcholine, phosphatidylserine and phosphatidylethanolamine and cholesterol in a ratio of about 4:1 to 7:

1. [5] The composition of claim 1, wherein the polyethylene glycol (PEG) is PEG-2000 or PEG-5000 and is present at a concentration of 7% by weight of the total composition. [6] Composition according to claim 1, wherein the sodium chloride is present in a concentration of 0.7% by weight of the total composition. [7] Composition according to claim 1, wherein the sodium phosphate is present in a concentration of 0.3% by weight of the total composition. [8] The composition of claim 1, wherein the pharmaceutically acceptable carrier or excipient is selected from the group consisting of water, saline and phosphate buffered saline.

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