top of page

Technical Review Article | Open Access | Published 8th October 2025

Brain Targeted Nanocarriers: A Revolutionary Approach for Treating Neurodegenerative Disorders


Muskan Tomar¹, Shashank Sharma²

¹Acropolis Institute of Pharmaceutical Education and Research, Indore, 453771, Madhya Pradesh. & ²Sri Aurobindo Institute of Pharmacy, Indore, 453555, Madhya Pradesh. EJPPS | 303 (2025) | https://doi.org/10.37521/ejpps30305


Abstract 

Neurodegenerative disorders, which include Alzheimer's, Parkinson's, and Huntington's, pose a significant worldwide health concern due to their gradual loss of neurons and cognitive impairment. The impermeability of the blood-brain barrier (BBB), the quick metabolism of medications, and non-specific delivery make traditional treatment approaches ineffective. Because they allow for site-specific drug administration, improve BBB penetration, and increase therapeutic efficacy while lowering systemic toxicity, brain-targeted nanocarriers provide a ground-breaking option. The techniques based on nanocarriers for the targeted therapy of neurodegenerative illnesses are thoroughly examined in this study. Current clinical uses, targeting ligands, surface changes, therapeutic payload types, administration methods, design considerations, and emerging developments are all covered. Active targeting technologies, such as nanoparticles modified with peptides and transferrins, are given particular attention. Clinical studies, regulatory obstacles, and the potential of gene-based nanotherapeutics are also highlighted in the study, providing fresh hope for the treatment of complicated CNS illnesses.

 

Key-words: Neurodegenerative diseases, Brain-targeted nanocarriers, Blood–brain barrier, Receptor-mediated targeting, Gene-based nanotherapeutics, CNS drug delivery


Introduction

The hallmark of neurodegenerative diseases (NDs) is the progressive loss of neurons, which typically results in death¹,². Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and other NDs are examples of progressive neuropsychiatric disorders³,⁴. NDs are frequently linked to the progressive loss of neurons and synaptic connections, which usually happens later in life⁵,⁶. Depending on where in the brain the neurons are being lost, many illnesses can be identified by their distinctive symptoms. The clinical prevalence of the patient and supporting data from magnetic resonance imaging (MRI) are necessary for the diagnosis of NDs⁷. There is a strong correlation between the degree of neuronal death and the start and progression of clinical symptoms. The hippocampus, a part of the brain involved in declarative episodic memory, exhibits neuronal loss early in AD⁸,⁹. Tremor, bradykinesia, and postural instability in Parkinson's disease (PD) can only be identified by the standard clinical trial after a substantial loss of 70–80% of dopaminergic neurons in the substantia nigra¹⁰,¹¹. But in multiple sclerosis, the activated immune responses (microglia) target the neuronal myelin sheaths, resulting in demyelination and impairing the conduction of neural signals. Additionally, they are to blame for a number of mental health issues¹²,¹³.


1.1 Challenges in Brain Drug Delivery - The extremely selective nature of the blood–brain barrier (BBB), which prevents most medications, including about 98% of small molecules, from penetrating the brain parenchyma, makes treating the central nervous system particularly difficult. This barrier significantly reduces drug penetrance and is made up of densely packed endothelial cells, astrocytes, pericytes, tight junctions, and active efflux transporters including P-glycoprotein and BCRP¹⁴,¹⁵. Furthermore, these permeability problems are made worse by the pathological changes associated with neurodegenerative illnesses, including as neuroinflammation, protein aggregation, oxidative stress, and altered transporter expression, which further increase delivery inefficiency into the brain¹⁶. Conventional methods of disrupting the blood-brain barrier, including targeted injections or osmotic opening, are frequently intrusive and dangerous. On the other hand, new approaches powered by nanotechnology, such as receptor-mediated nano systems, surface-functionalized nanoparticles, and innovative nano vehicle platforms, present potential avenues for targeted delivery. However, there are still translational issues, particularly with regard to constant BBB crossing efficiency, biocompatibility, long-term safety, and scalable production¹⁷.


1.2 Need for Targeted Nanocarrier Systems - The blood–brain barrier (BBB), which severely limits the entrance of therapeutic agents into the central nervous system and makes traditional drug administration essentially useless, necessitates the use of tailored nanocarrier systems in brain medication delivery. Liposomes, dendrimers, polymeric nanoparticles, micelles, quantum dots, and gold nanoparticles are examples of nanocarriers that are specifically designed to pass through this barrier while more effectively delivering and safeguarding medications¹⁸. These nanosystems improve the therapeutic index and lower systemic toxicity by increasing drug solubility and stability, extending circulation duration, and being functionalized for selective absorption by brain cells. Because the pathophysiology of neurodegenerative illnesses including Alzheimer's, Parkinson's, and Huntington's is multifactorial, delivery mechanisms that guarantee accurate localization, prolonged release, and effective BBB penetration are required. The critical need for thorough optimization of targeted nanocarrier platforms in CNS treatments is highlighted by the persistence of issues with long-term safety, biocompatibility, brain distribution characterization, and clinical translation despite these encouraging advancements.


2. Blood-Brain Barrier (BBB): An Obstacle in CNS Therapy - The blood-brain barrier (BBB) is a highly specialized contact between the central nervous system (CNS) and the blood. It is made up of endothelial cells joined by tight junctions and held up by a basement membrane, pericytes, and astrocytic end-feet. Ion homeostasis, nutrition transport, and neuronal protection are all tightly regulated by this multicellular architecture. In order to preserve optimal neuronal function, the BBB's primary job is to shield the central nervous system (CNS) from poisons, infections, and changes in blood composition. But this protective function also prevents around 98% of small-molecule medications and almost all major biologics from entering the market¹⁹.


2.1 Strategies to Overcome BBB for Drug Delivery - Novel pharmacological approaches have been created to circumvent or alter the BBB: To improve brain delivery, nanocarriers functionalized with targeting ligands (such as transferrin or LDLR ligands) take advantage of receptor-mediated transcytosis²⁰,²¹. Superior BBB penetration and targeting are provided by membrane-engineered nanoparticles, which are made utilizing cellular membranes (such as erythrocyte-derived vesicles) and improve biosafety. Nanocarriers must exhibit colloidal stability, resistance to protein binding and renal clearance, and long-term systemic persistence in order to translate well.


2.2 Pharmaceutical Relevance in CNS Therapy - The development of effective CNS therapies is hampered by the blood–brain barrier (BBB), particularly when it comes to parenteral formulations. Beyond just BBB penetration, nanocarrier platforms must guarantee colloidal stability in the bloodstream, controlled and sustained release of therapeutic payloads, biocompatibility to reduce immunogenicity, and, most importantly, scalability for manufacturing and regulatory compliance if drug delivery systems are to be clinically relevant. Designs for hybrid nanocarriers, such membrane-coated, biomimetic systems, provide encouraging answers to these problems. Membrane-engineered nanoparticles (CNPs), derived from tumour cells, leukocytes, or erythrocytes, in particular, not only avoid immune clearance but also enable effective BBB transit and CNS targeting. Large-scale manufacturing, batch repeatability, and regulatory approval, however, continue to be major obstacles to their successful translation²².


3. Nanocarriers in CNS Drug Delivery - Nanocarrier types include polymeric, lipid-based, and inorganic. A wide range of nanocarrier platforms have been studied for delivery to the central nervous system (CNS): Biodegradable polymers like PLGA, PLA, and PCL as well as natural polymers such as chitosan are examples of polymeric nanoparticles. Their high drug-loading capacity, adjustable release kinetics, and surface modification for targeted administration make them valuable²³,²⁴. Lipid-based carriers: Systems with superior biocompatibility include liposomes, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs). They are scalable for production, provide controlled release, and have good BBB crossing capabilities²⁵. Silica, magnetic iron oxide, gold nanoparticles, quantum dots, and carbon-based structures are all considered inorganic nanocarriers. Their BBB penetration, targeting, and imaging capabilities are improved by surface modifications (such as PEGylation and ligand attachment). But issues with toxicity and biodegradability still exist²⁶.


S.No.

Nanocarrier Type

Examples

Advantage

Limitations

References

1.

Polymeric Nanocarrier

PLGA, PEG, Chitosan nanoparticles

Biodegradable, sustained release, surface modification possible

Sometimes poor BBB penetration, may cause burst release.

[27]

2.

Lipid-based Nanocarrier

Liposomes, Solid Lipid Nanoparticles (SLNs), Nanostructured Lipid Carriers (NLCs)

Biocompatible, enhance solubility of hydrophobic drugs, improved BBB crossing

Physical instability, limited drug loading.

[28]

3.

Inorganic Nanocarrier

Gold nanoparticles, Silica nanoparticles, Quantum dots

High stability, imaging + therapy (theranostic use), easy surface functionalization

Potential toxicity poor solubility.

[29]

Table 1. Comparison of Different Types of Nanocarriers for CNS Drug Delivery


3.1 Surface Functionalization and Ligand Attachment - Functionalizing nanoparticles with surface ligands is frequently necessary to provide targeted transport across the BBB: Transferrin, lactoferrin, peptides, and antibodies are examples of ligand conjugates that use receptor-mediated transcytosis to enhance BBB uptake and CNS accumulation³⁰,³¹. Such functionalization increases therapeutic indices in neurodegenerative disease models and improves receptor-specific targeting for lipid-based systems³². PEGylation and other changes in polymeric and inorganic systems decrease opsonization, increase circulation time (stealth effect), and enable the attachment of targeted moieties such as aptamers, peptides, and antibodies.


Figure 1. Surface Functionalization and Ligand Attachment of Nanocarriers for CNS Drug Delivery
Figure 1. Surface Functionalization and Ligand Attachment of Nanocarriers for CNS Drug Delivery


3.2 Controlled Release and Stability in CNS - One of the biggest benefits of CNS drug delivery systems based on nanocarriers is controlled release. Nanocarriers have a prolonged release profile, sustaining therapeutic concentrations for longer periods of time than traditional formulations, which frequently experience fast clearance and cause fluctuating drug levels in the brain. The structural characteristics of polymeric nanoparticles, liposomes, and dendrimers enable the controlled release of medicines by degradation-mediated release or slow diffusion. Furthermore, by avoiding premature breakdown or opsonization, surface modifications like PEGylation and ligand attachment improve the stability of nanocarriers in systemic circulation. Because nanocarriers must pass across the blood–brain barrier (BBB) before releasing their payload, stability in the physiological milieu is essential; an early release would drastically diminish the effectiveness of treatment. According to recent research, nanocarriers provide a safer and more efficient method for long-term CNS treatments by extending drug half-life, lowering dose frequency, and minimizing systemic adverse effects³³.


4. Brain-Targeted Approaches in Nanocarriers - Brain-targeted nanocarriers have become a cutting-edge method to get over the blood-brain barrier's (BBB) limitations and improve treatment effectiveness for diseases of the central nervous system (CNS). Nanocarriers' physicochemical characteristics, including lipophilicity, particle size (less than 200 nm), and surface charge, as well as their enhanced permeability and retention (EPR) effect, are typically what enable passive targeting. These characteristics enable the nanocarriers to passively diffuse or accumulate in pathological sites where the blood-brain barrier is compromised, such as tumours or neuroinflammation³⁴. Active targeting strategies are being investigated since passive mechanisms alone are insufficient in the majority of neurodegenerative disorders because the blood-brain barrier is intact. The ability of nanocarriers functionalized with ligands such as transferrin, lactoferrin, insulin, or low-density lipoprotein (LDL) to bind to their corresponding overexpressed receptors on endothelial cells has made receptor-mediated targeting one of these extremely promising. This allows for receptor-mediated endocytosis and transcytosis into the brain parenchyma³⁵. Similar to this, systems that target glucose transporters (GLUT1) are commonly used since the brain requires a lot of glucose, which makes GLUT1 a good place for drug-loaded nanocarriers to enter. Using cell-penetrating peptides (CPPs) like TAT, penetratin, and RVG peptides, another innovative method increases the permeability of nanocarriers by encouraging direct translocation over the blood-brain barrier and into neurons with no damage³⁶. Antibody-modified nanocarriers, including those attached with anti-transferrin receptor antibodies (OX26) or anti-Aβ antibodies, further improve therapeutic selectivity and decrease off-target accumulation by enabling highly selective identification of neuronal or pathogenic targets. Schematic diagrams are frequently used to illustrate the mechanistic distinctions between these targeting strategies, which when combined—passive diffusion, receptor-mediated transport, CPP-facilitated entry, and antibody-mediated recognition—work in concert to improve CNS drug bioavailability, lower systemic toxicity, and accomplish site-specific delivery³⁷.


Figure 2. Brain-Targeted Nanocarrier Strategies, showing passive targeting, receptor-mediated targeting (e.g., transferrin, lactoferrin), and CPP/antibody-modified nanocarriers crossing the BBB.
Figure 2. Brain-Targeted Nanocarrier Strategies, showing passive targeting, receptor-mediated targeting (e.g., transferrin, lactoferrin), and CPP/antibody-modified nanocarriers crossing the BBB.

5. Nanocarrier Strategies for Major Neurodegenerative Disorders - The intricacy of the central nervous system (CNS) and the restricted nature of the blood–brain barrier (BBB) make neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) some of the most difficult therapeutic areas. Novel approaches to delivering therapeutic molecules straight to the brain, enhancing medication bioavailability, and facilitating targeted molecular interventions are provided by nanocarrier-based drug delivery.


5.1 Alzheimer’s Disease (AD)- The intact BBB and extensive pathology in Alzheimer's disease, which is characterized by amyloid-β (Aβ) plaques, tau pathology, and neuroinflammation, provide special difficulties for medication transport. Novel pathways are provided by nanocarriers: Caffeic acid-loaded formulations of transferrin-functionalized liposomes have shown promise in preventing the production of Aβ fibrils and may be able to penetrate the blood-brain barrier through Tf receptor-mediated transcytosis³⁸. Dual-targeted with anti-transferrin receptor and anti-Aβ monoclonal antibodies, PEGylated immunoliposomes cross the blood-brain barrier in vivo and improve the brain's absorption of therapeutic payloads³⁹. Because of their high loading capacity and bilayer shape, lipid-based nanoparticles (LBNs) enable effective BBB transcytosis and may increase treatment effectiveness in AD by overcoming the restricted brain delivery of traditional medications⁴⁰.


5.2 Parkinson’s Disease (PD) - Parkinson's disease causes a gradual loss of dopaminergic neurons; nanocarriers can overcome the drawbacks of existing therapies: In order to improve the transport of dopamine, L-DOPA, or neuroprotective medicines to afflicted brain areas, emerging nanocarrier platforms - such as those examined in the PD nanomedicine literature - are progressively made to cross the blood-brain barrier⁴¹. Designed for efficient BBB penetration through adsorptive processes, bioinspired chitosan–albumin–dopamine nanoparticles exhibit regulated dopamine delivery and advantageous physicochemical characteristics (38–190 nm, + 73 mV zeta potential)⁴². Polymeric and lipidic nanocarrier-based L-DOPA systems have the potential to improve brain transport and regulated release, hence resolving persistent dosage issues in Parkinson's disease⁴³.


5.3 Huntington’s Disease (HD) - Mutant huntingtin aggregation causes HD, a hereditary neurological illness; gene-silencing techniques using nanocarriers provide hope: In HD animals, chitosan-enriched siRNA nanoparticles given intranasally dramatically decreased mutant HTT expression (~50%) in a variety of brain areas. Huntingtin mRNA is targeted by self-assembling amphiphilic β-cyclodextrin nanoparticles loaded with siRNA, which efficiently and minimally cytotoxically decrease its expression ⁴⁴. Lipid, polymer, and inorganic nanocarriers are generally being investigated for the safe and effective transport of siRNA to the central nervous system⁴⁵.


5.4 Multiple Sclerosis (MS) - Immunomodulatory treatments are required for neuroinflammatory demyelination in MS; nanotechnology provides focused approaches: In the animal MS model, tolerogenic PLGA nanoparticles and liposomes containing immunomodulators (like rapamycin) and antigens (like MOG peptides) have shown suppression of EAE, lowering illness incidence and fostering immunological tolerance⁴⁶. Future treatment options for multiple sclerosis may be provided by the exploration of nanovesicles and artificial vesicles for immunomodulation and targeted delivery⁴⁷. Nano-engineering of stem cells, such as scaffolds and surface alteration, is another emerging technique to promote oligodendrocyte precursor proliferation and remyelination in multiple sclerosis⁴⁸.


5.5 Amyotrophic Lateral Sclerosis (ALS)- In ALS models, riluzole-loaded solid lipid nanoparticles (SLNs or NLCs) offer improved brain targeting, extended release, and less toxicity. Because it improves transport and cellular absorption without causing considerable cytotoxicity, edaravone encapsulated in nanocarriers offers potential as an alternate ALS treatment. In-depth analyses demonstrate how nanotechnology might improve BBB crossing, bioavailability, and real-time targeting to reinvigorate inadequate ALS treatments⁴⁹,⁵⁰,⁵¹,⁵².


Figure 3. Nanocarrier-based therapeutic strategies for major neurodegenerative diseases
Figure 3. Nanocarrier-based therapeutic strategies for major neurodegenerative diseases

(This diagram shows how nanocarriers are used in various neurodegenerative diseases. The anti-amyloid and neuroprotective administration of transferrin/Aβ-targeted liposomes is employed for Alzheimer's disease. Biodegradable nanoparticles in Parkinson's disease help transport dopamine and L-DOPA. HTT gene silencing is the focus of siRNA/CRISPR-based nanocarriers for Huntington's disease. In MS, tolerogenic nanoparticles function as immunomodulators. Therapeutic efficacy for Amyotrophic Lateral Sclerosis (ALS) is improved by exosome/antibody systems and riluzole/edaravone nanocarriers)


6. Therapeutic Payloads in Brain-Targeted Nanocarriers - The therapeutic payloads that can be encapsulated by nanocarriers intended for brain administration range from tiny chemicals to sophisticated biological agents. Although small compounds like donepezil, resveratrol, and curcumin have demonstrated neuroprotective benefits, they are poorly soluble and penetrate the blood-brain barrier; liposomes and polymeric nanoparticles, which are nanocarriers, enhance their stability, bioavailability, and targeted delivery to sick brain areas. Nucleic acid therapies are becoming more and more popular, going beyond tiny molecules. Although siRNA, miRNA, and CRISPR payloads can alter gene expression by reversing genetic mutations in neurodegenerative diseases or silencing harmful genes (such as mutant huntingtin in Huntington's disease), their instability and vulnerability to enzymatic degradation make protective carriers like lipid nanoparticles or dendrimers necessary to ensure effective CNS delivery. Similar to this, peptides, proteins, and antibodies are another potent class of therapeutics that have high specificity for pathological targets like tau, α-synuclein aggregates, or amyloid-β. Their delivery via nanocarriers improves their BBB crossing, extends circulation, and enables conjugation with targeting ligands (such as transferrin or lactoferrin) for precision therapy in Parkinson's and Alzheimer's diseases. When combined, the incorporation of several therapeutic payloads into brain-targeted nanocarriers offers a revolutionary method for treating intricate neurodegenerative diseases⁵³.


7. Administration Routes and Formulations - For the treatment of neurodegenerative illnesses, administration methods and formulations are crucial in guaranteeing that nanocarriers efficiently reach the brain. Bypassing the blood–brain barrier (BBB) via the olfactory and trigeminal pathways, intranasal administration has become a viable non-invasive method that allows therapeutic agent-loaded nanoparticles to accumulate quickly in the brain⁵⁴. Intravenous injection uses nanocarriers functionalized with ligands or surface coatings to breach the blood-brain barrier and provide targeted distribution, whereas intrathecal administration directly delivers nanosystems into the cerebrospinal fluid. Hydrogels, lipid nanoparticles, and polymeric formulations are examples of injectable nanosystems for the central nervous system that provide controlled and prolonged release, lowering systemic toxicity and enhancing therapeutic efficacy. Particularly useful for long-term treatment plans in conditions such as Parkinson's and Alzheimer's, when continuous dosage is necessary, are injectable formulations⁵⁵.


Figure 4. Administration Routes and Nanocarrier Formulations for Brain Delivery
Figure 4. Administration Routes and Nanocarrier Formulations for Brain Delivery

8. Current Status: Clinical Trials and Commercial Products - Although its application in clinical settings is currently restricted, the translation of brain-targeted nanocarrier systems is progressing. The practical potential of nanocarrier therapies for neurodegenerative and central nervous system illnesses is being investigated through ongoing clinical trials. In two Phase 2 trials, for example, CNM-Au8, a gold nanocrystal formulation, evaluated its therapeutic effects on neuronal redox states in Parkinson's disease (REPAIR-PD) and Amyotrophic Lateral Sclerosis (ALS) (RESCUE-ALS)⁵⁶. Other noteworthy studies include AGuIX nanoparticles in combination with radiation and Temozolomide in early-phase trials for glioblastoma, and APH-1105, an experimental medication based on nanocarriers, in Phase 2 for Alzheimer's disease (NCT03806478). These clinical studies represent significant turning points in the clinical assessment of CNS-targeted nanotherapeutics, despite the fact that they are exploratory and that data are still pending or restricted. FDA-Approved and Marketed Nanoformulations, on the other hand, show the viability of nanomedicine platforms while highlighting successful uses mostly outside the neurodegenerative sector. Since its approval as a subcutaneous polymer–protein conjugate for multiple sclerosis in the United States in 1996, Copaxone® (glatiramer acetate) continues to be a trailblazing example⁵⁷,⁵⁸. Additional formulations pertaining to the brain include Opaxio®, a paclitaxel–SLN combination created to treat glioblastoma, and DepoCyt®, an injectable liposomal cytarabine used for lymphomatous meningitis. Plegridy®, a PEGylated interferon-β-1a conjugation, is also used subcutaneously for multiple sclerosis (MS) and has been shown to have improved stability and decreased frequency of dosage. Products like liposomal antifungals (AmBisome®, Abelcet®), cancer-targeted liposomal medicines (DaunoXome®, Doxil®), and nanocrystal-based drugs (e.g., Avinza®, Ritalin LA®, Focalin XR®) further demonstrate the wider clinical usefulness of nanocarrier platforms outside CNS utilization⁵⁹.


9. Limitations and Challenges - Nanocarrier systems have a promising function in the transport of drugs to the central nervous system (CNS), but they are limited by a number of issues that prevent extensive clinical translation.

Nanotoxicity and Immunogenicity: The nanotoxicity linked to the long-term buildup of nanoparticles in the liver, spleen, and brain tissue is one of the main worries. According to studies, if inorganic nanocarriers (such as carbon-based systems, silica, or gold) are not correctly constructed, they may cause neuroinflammation, oxidative stress, or disruption of neuronal communication. Furthermore, functional groups and surface coatings may cause immunogenic reactions, changing microglial activity or causing the production of systemic cytokines, which raises questions about safety in long-term neurodegenerative treatments.

Cost and Scalability: Despite the effectiveness of laboratory-scale nanocarrier manufacturing, industrial production scaling up is still expensive and technically challenging. Maintaining consistency in nanoparticle size, charge, drug encapsulation effectiveness, and batch-to-batch stability are among the difficulties. For instance, complex production equipment such as high-pressure homogenizers or microfluidic systems are needed to produce polymeric nanoparticles and liposomes, which raises prices and makes them less affordable for big patient populations. Additionally, many formulations (such as liposomal medicines) have a short shelf life and cold-chain requirements, which increase logistical constraints and make large-scale deployment challenging⁵⁹.

Regulatory Challenges: The regulatory environment is arguably the biggest obstacle. Nanomedicines, in contrast to traditional medications, are diverse and intricate, with distinct pharmacokinetics, biodistribution, and long-term safety profiles that are still being worked out. There are presently no widely accepted standards for evaluating CNS nanomedicines, and regulatory agencies such as the FDA and EMA evaluate nanocarriers on an individual basis. Developers are left in the dark and approval processes are slowed down by the absence of defined norms. Furthermore, more stringent monitoring and post-marketing surveillance are required due to ethical concerns regarding patient safety, particularly with regard to experimental medicines that target the brain⁶⁰.


10. Future Perspectives and Conclusion

Nanocarrier-based therapies have the potential to revolutionize the treatment of neurodegenerative illnesses by facilitating effective, long-lasting, and targeted drug delivery over the blood-brain barrier (BBB). According to expectations, future studies will concentrate on multifunctional nanocarriers that combine therapeutic and diagnostic properties (theranostics), enabling real-time tracking of medication response and illness development. The use of personalized nanomedicine offers still another important viewpoint. Here, patient-specific biomarkers, genetic analysis, and AI-driven modeling may be used to create unique nanocarriers that are safer and more effective. Furthermore, when administered via brain-targeted nanoparticles, gene-based payloads like siRNA, CRISPR-Cas9, and mRNA are expected to completely alter the way that ALS, Parkinson's disease, and Alzheimer's disease are treated. However, issues with nanotoxicity, large-scale repeatability, cost-effectiveness, and regulatory compliance must be addressed in order to move from bench to bedside. To speed up clinical approval and commercialization, uniform preclinical models and harmonized regulatory frameworks are still desperately needed. Notwithstanding these obstacles, the direction of ongoing studies and clinical trials points to a bright future in which nanocarriers will play a key role in next-generation CNS treatments, providing fresh hope for the treatment of intricate and presently incurable neurodegenerative diseases.

References


  1. Gadhave DG, Sugandhi VV, Kokare CR. Potential biomaterials and experimental animal models for inventing new drug delivery approaches in the neurodegenerative disorder: Multiple sclerosis. Brain Research. 2024 Jan 1; 1822:148674.

  1. Lamptey RN, Chaulagain B, Trivedi R, Gothwal A, Layek B, Singh J. A review of the common neurodegenerative disorders: current therapeutic approaches and the potential role of nanotherapeutics. International journal of molecular sciences. 2022 Feb 6;23(3):1851.

  1. Choonara YE, Pillay V, Du Toit LC, Modi G, Naidoo D, Ndesendo VM, Sibambo SR. Trends in the molecular pathogenesis and clinical therapeutics of common neurodegenerative disorders. International Journal of Molecular Sciences. 2009 Jun 3;10(6):2510-57.

  1. Hui BS, Zhi LR, Retinasamy T, Arulsamy A, Law CS, Shaikh MF, Yeong KY. The role of interferon-α in neurodegenerative diseases: a systematic review. Journal of Alzheimer’s Disease. 2023 Jul 25;94(s1):S45-66.

  1. Pant S, Kapri A, Nain S. Pyrimidine analogues for the management of neurodegenerative diseases. European Journal of Medicinal Chemistry Reports. 2022 Dec 1;6:100095.

  1. Tanaka M, Toldi J, Vécsei L. Exploring the etiological links behind neurodegenerative diseases: Inflammatory cytokines and bioactive kynurenines. International journal of molecular sciences. 2020 Mar 31;21(7):2431.

  1. Huang P, Zhang M. Magnetic resonance imaging studies of neurodegenerative disease: from methods to translational research. Neuroscience Bulletin. 2023 Jan;39(1):99-112.

  1. Jiménez-Balado J, Eich TS. GABAergic dysfunction, neural network hyperactivity and memory impairments in human aging and Alzheimer’s disease. In Seminars in cell & developmental biology 2021 Aug 1 (Vol. 116, pp. 146-159). Academic Press.

  1. Shankar GM, Walsh DM. Alzheimer's disease: synaptic dysfunction and Aβ. Molecular neurodegeneration. 2009 Nov 23;4(1):48.

  1. Clarke CE. Medical management of Parkinson's disease. Journal of Neurology, Neurosurgery & Psychiatry. 2002 Mar 1;72(supply 1):i22-7.

  1. DeMaagd G, Philip A. Parkinson’s disease and its management: part 1: disease entity, risk factors, pathophysiology, clinical presentation, and diagnosis. Pharmacy and therapeutics. 2015 Aug;40(8):504

  1. Gadhave DG, Sugandhi VV, Kokare CR. Potential biomaterials and experimental animal models for inventing new drug delivery approaches in the neurodegenerative disorder: Multiple sclerosis. Brain Research. 2024 Jan 1;1822:148674.

  1. Gadhave DG, Kokare CR. Nanostructured lipid carriers engineered for intranasal delivery of teriflunomide in multiple sclerosis: optimization and in vivo studies. Drug development and industrial pharmacy. 2019 May 4;45(5):839-51.

  1. Liu S, Jin X, Ge Y, Dong J, Liu X, Pei X, Wang P, Wang B, Chang Y, Yu XA. Advances in brain-targeted delivery strategies and natural product-mediated enhancement of blood–brain barrier permeability. Journal of Nanobiotechnology. 2025 May 26;23(1):382.

  1. Bors LA, Erdő F. Overcoming the blood–brain barrier. challenges and tricks for CNS drug delivery. Scientia Pharmaceutica. 2019;87(1):6.

  1. Liu J, Wang T, Dong J, Lu Y. The blood–brain barriers: novel nanocarriers for central nervous system diseases. Journal of Nanobiotechnology. 2025 Feb 26;23(1):146.

  1. Mhaske A, Shukla S, Ahirwar K, Singh KK, Shukla R. Receptor-assisted nanotherapeutics for overcoming the blood–brain barrier. Molecular neurobiology. 2024 Nov;61(11):8702-38.

  1. Alotaibi BS, Buabeid M, Ibrahim NA, Kharaba ZJ, Ijaz M, Noreen S, Murtaza G. Potential of nanocarrier-based drug delivery systems for brain targeting: A current review of literature. International Journal of Nanomedicine. 2021 Nov 11:7517-33.

  1. Kadry H, Noorani B, Cucullo L. A blood–brain barrier overview on structure, function, impairment, and biomarkers of integrity. Fluids and Barriers of the CNS. 2020 Nov 18;17(1):69.

  1. Teixeira MI, Lopes CM, Amaral MH, Costa PC. Surface-modified lipid nanocarriers for crossing the blood-brain barrier (BBB): A current overview of active targeting in brain diseases. Colloids and Surfaces B: Biointerfaces. 2023 Jan 1;221:112999.

  1. Senanayake D, Yapa P, Dabare S, Munaweera I. Precision targeting of the CNS: recent progress in brain-directed nanodrug delivery. RSC advances. 2025;15(32):25910-28

  1. Yuan S, Hu D, Gao D, Butch CJ, Wang Y, Zheng H, Sheng Z. Recent advances of engineering cell membranes for nanomedicine delivery across the blood–brain barrier. Journal of Nanobiotechnology. 2025 Jul 8;23(1):493.

  1. Lu H, Zhang S, Wang J, Chen Q. A review on polymer and lipid-based nanocarriers and its application to nano-pharmaceutical and food-based systems. Frontiers in nutrition. 2021 Dec 1;8:783831.

  1. Maher R, Moreno-Borrallo A, Jindal D, Mai BT, Ruiz-Hernandez E, Harkin A. Intranasal polymeric and lipid-based nanocarriers for CNS drug delivery. Pharmaceutics. 2023 Mar;15(3):746.

  1. Liu J, Wang T, Dong J, Lu Y. The blood–brain barriers: novel nanocarriers for central nervous system diseases. Journal of Nanobiotechnology. 2025 Feb 26;23(1):146.

26. Lv W, Liu Y, Li S, Lv L, Lu H, Xin H. Advances of nano drug delivery system for the theranostics of ischemic stroke. Journal of nanobiotechnology. 2022 May 31;20(1):248.

  1. Li Y, Xiong J, Guo W, Jin Y, Miao W, Wang C, Zhang H, Hu Y, Huang H. Decomposable black phosphorus nano-assembly for controlled delivery of cisplatin and inhibition of breast cancer metastasis. Journal of Controlled Release. 2021 Jul 10;335:59-74.

  1. Alhajj N, O'Reilly NJ, Cathcart H. Development and characterization of a spray-dried inhalable ciprofloxacin-quercetin co-amorphous system. International Journal of Pharmaceutics. 2022 Apr 25;618:121657.


  1. Zhang Y, Cheng X, Jiang X, Urban JJ, Lau CH, Liu S, Shao L. Robust natural nanocomposites realizing unprecedented ultrafast precise molecular separations. Materials Today. 2020 Jun 1;36:40-7.

  1. Ding S, Khan AI, Cai X, Song Y, Lyu Z, Du D, Dutta P, Lin Y. Overcoming blood–brain barrier transport: Advances in nanoparticle-based drug delivery strategies. Materials today. 2020 Jul 1;37:112-25.

  1. Teixeira MI, Lopes CM, Amaral MH, Costa PC. Surface-modified lipid nanocarriers for crossing the blood-brain barrier (BBB): A current overview of active targeting in brain diseases. Colloids and Surfaces B: Biointerfaces. 2023 Jan 1;221:112999.

  1. Ganesan M, Tenchov R, Iyer KA, Ralhan K, Diaz LL, Bird RE, Ivanov J, Zhou Q. Nanoscale materials at work: Mapping emerging applications in energy, medicine, and beyond.

  1. Saraiva C, Praça C, Ferreira R, Santos T, Ferreira L, Bernardino L. Nanoparticle-mediated brain drug delivery: Overcoming blood–brain barrier to treat neurodegenerative diseases. Journal of controlled release. 2016 Aug 10;235:34-47

  1. Newstead S, Lewis J, Roderique-Davies G, Heirene RM, John B. The paradox of the frontal lobe paradox. a scoping review. Frontiers in Psychiatry. 2022 Jul 22;13:913230.

  1. Xu Y, Zhuang Z, Zheng H, Shen Z, Gao Q, Lin Q, Fan R, Luo L, Zheng W. Glutamate chemical exchange saturation transfer (GluCEST) magnetic resonance imaging of rat brain with acute carbon monoxide poisoning. Frontiers in Neurology. 2022 May 19;13:865970.

  1. D’Angelo H, Ammerman A, Gordon-Larsen P, Linnan L, Lytle L, Ribisl KM. Sociodemographic disparities in proximity of schools to tobacco outlets and fast-food restaurants. American journal of public health. 2016 Sep;106(9):1556-62.

  1. Feng H, Wu YQ, Xu YS, Wang KX, Qin XM, Lu YF. LC-MS-based metabolomic study of oleanolic acid-induced hepatotoxicity in mice. Frontiers in Pharmacology. 2020 May 26;11:747.

  1. Puranik N, Yadav D, Song M. Advancements in the application of nanomedicine in Alzheimer’s disease: a therapeutic perspective. International Journal of Molecular Sciences. 2023 Sep 13;24(18):14044.

  1. Chopra H, Bibi S, Singh I, Kamal MA, Islam F, Alhumaydhi FA, Emran TB, Cavalu S. Nanomedicines in the management of Alzheimer’s disease: current view and future prospects. Frontiers in Aging Neuroscience. 2022 Jul 8;14:879114.

  1. Jang YJ, Kang SJ, Park HS, Lee DH, Kim JH, Kim JE, Kim DI, Chung CH, Yoon JK, Bhang SH. Drug delivery strategies with lipid-based nanoparticles for Alzheimer’s disease treatment. Journal of nanobiotechnology. 2025 Feb 10;23(1):99.

  1. Yadav VK, Dhanasekaran S, Choudhary N, Nathiya D, Thakur V, Gupta R, Pramanik S, Kumar P, Gupta N, Patel A. Recent advances in nanotechnology for Parkinson’s disease: diagnosis, treatment, and future perspectives. Frontiers in Medicine. 2025 Jan 22;12:1535682.

  1. Razzak AA, Al-Garawi ZS, Haider AJ, Hassan FN. New nanomanufacturing strategy through bioinspired design, for promising treatment of Parkinson’s disease. Scientific Reports. 2025 Feb 26;15(1):6904.

  1. van Vliet EF, Knol MJ, Schiffelers RM, Caiazzo M, Fens MH. Levodopa-loaded nanoparticles for the treatment of Parkinson's disease. Journal of Controlled Release. 2023 Aug 1;360:212-24.

  1. Godinho BM, Ogier JR, Darcy R, O’Driscoll CM, Cryan JF. Self-assembling modified β-cyclodextrin nanoparticles as neuronal siRNA delivery vectors: Focus on Huntington’s disease. Molecular pharmaceutics. 2013 Feb 4;10(2):640-9.

  1. Moazzam M, Zhang M, Hussain A, Yu X, Huang J, Huang Y. The landscape of nanoparticle-based siRNA delivery and therapeutic development. Molecular Therapy. 2024 Feb 7;32(2):284-312.

  1. Chountoulesi M, Demetzos C. Promising nanotechnology approaches in treatment of autoimmune diseases of central nervous system. Brain Sciences. 2020 Jun 2;10(6):338.

  1. Nuzzo D, Picone P. Multiple sclerosis: focus on extracellular and artificial vesicles, nanoparticles as potential therapeutic approaches. International Journal of Molecular Sciences. 2021 Aug 18;22(16):8866.

  1. Ghosh S, Bhatti GK, Sharma PK, Kandimalla R, Mastana SS, Bhatti JS. Potential of nano-engineered stem cells in the treatment of multiple sclerosis: a comprehensive review. Cellular and Molecular Neurobiology. 2024 Dec;44(1):6.

  1. Aghajani J, Deljavan Y, Haghighatdoust M. Drug Delivery Options for Riluzole in the Treatment of Amyotrophic Lateral Sclerosis. Neurology Letters. 2025 Jan 27;4(1):12-6.

  1. Dhariwal R, Jain M, Mir YR, Singh A, Jain B, Kumar P, Tariq M, Verma D, Deshmukh K, Yadav VK, Malik T. Targeted drug delivery in neurodegenerative diseases: the role of nanotechnology. Frontiers in Medicine. 2025 Jan 29;12:1522223.

  1. Aguiar B, Alfenim AR, Machado CS, Moreira J, Pinto M, Otero-Espinar FJ, Borges F, Fernandes C. Exploring Nano-Delivery Systems to Enhance the Edaravone Performance in Amyotrophic Lateral Sclerosis Treatment. International Journal of Molecular Sciences. 2025 Feb 27;26(5):2146.

  1. Wang GY, Rayner SL, Chung R, Shi BY, Liang XJ. Advances in nanotechnology-based strategies for the treatments of amyotrophic lateral sclerosis. Materials Today Bio. 2020 Mar 1;6:100055

  1. Mehanny M, Hathout RM, Geneidi AS, Mansour S. Exploring the use of nanocarrier systems to deliver the magical molecule; curcumin and its derivatives. Journal of controlled release. 2016 Mar 10;225:1-30.

  1. Sajeesh S, Bouchemal K, Marsaud V, Vauthier C, Sharma CP. Cyclodextrin complexed insulin encapsulated hydrogel microparticles: An oral delivery system for insulin. Journal of Controlled Release. 2010 Nov 1;147(3):377-84.

  1. Gnjidic D, Husband A, Todd A. Challenges and innovations of delivering medicines to older adults. Advanced Drug Delivery Reviews. 2018 Oct 1;135:97-105.

  1. Duan L, Li X, Ji R, Hao Z, Kong M, Wen X, Guan F, Ma S. Nanoparticle-based drug delivery systems: an inspiring therapeutic strategy for neurodegenerative diseases. Polymers. 2023 May 5;15(9):2196.

  1. Meyer AH, Feldsien TM, Mezler M, Untucht C, Venugopalan R, Lefebvre DR. Novel developments to enable treatment of CNS diseases with targeted drug delivery. Pharmaceutics. 2023 Mar 29;15(4):1100.

  1. Zeeshan M, Mukhtar M, Ain QU, Khan S, Ali H. Nano pharmaceuticals: A boon to the brain-targeted drug delivery. Pharmaceutical Formulation Design-Recent Practices. 2019 Jun 4:1-5.

  1. Lee JH, Kim HS, Joo SH. Isolated A1 pulley rupture of left fourth finger in kendo players: two case reports. Annals of rehabilitation medicine. 2015 Oct 26;39(5):838-43.

  1. Clayville LR. Influenza update: a review of currently available vaccines. Pharmacy and Therapeutics. 2011 Oct;36(10):659.



Author Information


Authors: Muskan Tomar¹, Shashank Sharma²

¹, Acropolis Institute of Pharmaceutical Education and Research, Indore, 453771, Madhya Pradesh.

², Sri Aurobindo Institute of Pharmacy, Indore, 453555, Madhya Pradesh.


Corresponding Author: Shashank Sharma, Assistant Professor

Address: Sri Aurobindo Institute of Pharmacy, Indore, 453555, Madhya Pradesh.




 
 
 

Comments

bottom of page