INTRODUCTION:

Neurological diseases are a major cause of mortality and disability worldwide, accounting for 12% of all fatalities. For a considerable amount of time, neuroinflammatory illness (INF) has been recognized as a common element of neurological disorders, including multiple sclerosis (MS), Parkinson's disease (PD), and Alzheimer's disease (AD). The blood-brain barrier prevents several potentially helpfull drugs for neurological conditions from reaching the brain in sufficient amounts.^1-4Millions of people of all ages and genders are impacted by cancer, which makes it an illness with several problems. There are many factors that contribute to cancer, but genetics and environment rank first and second, respectively.⁵ Although there has been extensive research into the creation of medicines for cancer and CNS illnesses, the majority of users may not benefit much from these treatments due to low absorption rates, inadequate concentrations, and a lack of customized therapy. As such, novel treatment approaches are imperative to target the challenges that unquestionably eradicate diseased tissues while sparing healthy tissue. Over the past few years, scientists, pharmacists, and chemists from all over the world have focused on developing nanotechnology systems,^1,6 which have applications in many medical fields,^7,8 including drug delivery. Present research is being done on biopolymers as nanoparticles as a potential alternative for the targeted delivery of drugs⁹ or macromolecules in the biological system.¹⁰ Biopolymer NPs have demonstrated considerable effectiveness in producing bioactive molecules¹¹ for both in vitro and in vivo applications. Nano biopolymers are also helpful in the field of enzyme replacement therapy. The effects of dementia affect about 24 million people worldwide, with AD accounting for 60% of cases.⁷ Memory and learning problems are common in Alzheimer's sufferers. Post-mortem examinations of human brain tissue have revealed net cerebral decay, a condition that shows a deficiency of neurons and the presence of various neuronal extracellular plaques and intracellular neurofibrillary tangles. This decay is primarily found in the front-facing and transient flaps, including the hippocampus.⁶ Nevertheless, even though the pathophysiology of AD is understood, neither its cause nor its mechanism are understood. Consequently, the therapy of AD is limited to managing its symptoms. Extreme adverse effects include hyperkinesia, bradykinesia, unbending nature, and a resting quake, which are brought on by the loss of nigrostriatal dopaminergic neurons in the midbrain .⁷ Despite being the second most common chronic and progressive non-degenerative illness, PD has a significant social and economic impact on the vast majority of those who are afflicted.⁸Dopamine (DA) neurons that deteriorate with time release less DA in the brain's substantia nigra and ventral tegmental area. PD patients might have a variety of symptoms, such as slowness of movement, tremor, and stiffness. Sometimes it might be challenging to distinguish PD from other disorders that share many of the same symptoms.

The term "Parkinsonism" has therefore evolved to refer to a variety of neurological disorders. There are two types of Parkinsonism symptoms: primary and secondary. The most prevalent type of primary Parkinsonism, idiopathic Parkinsonism, lacks a known cause. Secondary Parkinsonism can result from several illnesses, such as multiple system atrophy, progressive supranuclear palsy, and others; however, drug-induced Parkinsonism following cerebrovascular illness is the most common. Under the general category of Parkinsonism, vascular Parkinsonism is a unique clinical entity with a wide variety of clinical symptoms and a variable natural history. Strong evidence also supports the inclusion of clock genes in PD.⁸ Due to a greater understanding of the pathophysiology of many diseases, there has been a notable expansion in the pursuit of novel therapies that alter illness.

Techniques for preparation of nanoparticles

silver nanoparticles(AgNPs) Silver has been used extensively in the medical field because its nanoscale form displays remarkably unique physicochemical and biological properties. Any biological agents that lower Ag ions in solutions become essential for producing AgNPs that are acceptable to the environment. The integrated biological reaction with phenols, vitamins, amino acids, or proteins enabled the reduction of AgNPs.¹²

copper nanoparticles (CuNPs) CuNPs enhance antibacterial, antifungal, and antiviral activities and are valued for their electrical conductivity and photocatalytic properties. They are used in wastewater treatment, DNA analysis, and as antioxidants, with production often involving various plants due to their bioactive components.¹³

Gold nanoparticles (AuNPs) AuNPs are notable for their chemical and optical properties, making them promising for therapeutic and diagnostic use. They are utilized in bioimaging, photothermal therapy, and drug delivery. Green-synthesized AuNPs, with their non-toxic nature and effective catalytic reactions, are particularly beneficial for enhancing medication and gene delivery.^[11] The AuNPs has several benefits for the advancement of biomedicine, including the ability to quickly identify and diagnose cardiac problems.

Applications of AgNPs The beneficial use of AgNPs has been the subject of numerous literary works. AgNPs have been shown to have uses in the field of biomedicine, which includes bioimaging, dental technology, and cancer treatment, among other things. AgNPs have garnered attention in the field of cancer therapy due to their unusual chemical and physical properties.¹⁴ AgNPs effectively target cancer cells in various organs and are valued for their affordability and versatility. They are used in environmental applications like aqua mining, agriculture, and wastewater treatment, where they promote photolysis and adsorption to clean water.¹⁵

Green synthesis of nanoparticles:

Green synthesis is an environmentally benign and biocompatible process that is commonly performed using plant extracts, bacteria, yeast, or capping agents/stabilizers.¹⁶ Although traditional processes were adopted many years ago, research has indicated that green approaches—which offer low costs, easy characterization, and lower failure chances—are more effective in creating innovative medications.

Plant-based NPs synthesis is a straightforward process that involves the production of a metal salt using plant extract and reaction times ranging from a few minutes to several hours at room temperature. Over the past ten years, this method has received a lot of attention, especially for silver (Ag) and gold (Au) NPs, which are safer than other metallic NPs. Green synthesis strategies are quite attractive since they can reduce NPs toxicity.¹⁷ Many metal NPs, such as copper (Cu), zinc (Zn), iron (Fe), silver (Ag), magnesium (Mg), palladium (Pd), and gold (Au), are used in green synthesis.

Metal NPs can be synthesized using bacteria like Bacillus subtilis and fungi such as Fusarium oxysporum. Key pre-requisites include safe materials, effective stabilizers, and eco-friendly solvents. Biosynthesis with bacteria and plants, using parts like stems and leaves, provides a secure and sustainable method for biomedical applications (fig. 1).¹⁸

Possible mechanisms involved in nanoparticles synthesis It is vital to understand the process and metabolic pathways that contribute to the manufacture of metal NPs to establish a good strategy for NPs synthesis as shown in (fig. 2). Many other theories about making NPs have existed in the last few years. However, the specific process underlying the biological metal NPs synthesis is not yet cleared, and further research is required to determine this. Secondary metabolites and proteins found in the water-soluble parts of Geranium leaves were examined. In another study, the flavonoids or polyphenols of leaves were responsible for synthesizing AuNPs and AgNPs.¹⁹

Role of nanotechnology in neurodegenerative disorders Because of the aging population and the rising prevalence of CNS illnesses such as Alzheimer's, Parkinson's, and strokes, the healthcare industry is facing a massive challenge. Despite advances in our understanding of their pathogenesis, early detection and treatment of CNS disorders remain challenging, and current treatments mostly target their symptoms. Many of the newly created drugs (such proteins and peptides) may not work because of their inadequate pharmacokinetics and non-specific targeting, which increases the possibility of side effects. These problems stem from biological barriers like the blood-brain barrier (BBB). It prevents most substances from the blood from going to the brain by acting as a barrier between the CNS and peripheral circulation.^[18] Moreover, the majority of CNS diseases, such as strokes, PD and AD, have been linked to BBB dysfunction. Changes in the transport system and enzymes are a major contributor and exacerbator of sickness development, even though it is uncertain if BBB failure is the fundamental cause of illness formation. On the other hand, current advances in nanotechnology suggest that it may be a useful tool for diagnosing and treating CNS disorders. The term "nanotechnology" refers to the control or manipulation of materials or devices that are designed at the nanoscale scale (one billionth of a meter).¹⁹Nanomaterials, with their altered surface properties, offer significant advantages for CNS disease diagnosis and treatment. They provide high drug-loading capacity, a large surface area-to-volume ratio, and options for targeted and sustained drug delivery. Key factors for effective use include surface chemistry, size, and charge, while ideal nanoparticles should be biocompatible, low in toxicity, and capable of efficient drug binding and transport. A study on the transport of drugs to specific sites has led to the non-invasive distribution of the prescribed dosage to designated regions, targeted and focused administration the therapeutic dose at the location of pharmacological activity.There are currently non-invasive techniques, such as intranasal administration with drug modification to promote BBB permeability²⁰ as well as invasive ones, such as intraventricular or intracerebral injection or implantation, and infusion. Disruption may be effective in certain circumstances to cross the BBB.²¹ Small therapeutic compound have recently been shown to be able to pass across the BBB in AD and MS. Researchers in neuropharmaceuticals are working to understand the processes of receptor mediated and adsorptive transcytosis, as well as all the inherent physicochemical features of neuropharmeuticals. As a result, this might lead to new therapies that are more effective in crossing the BBB.^22,23

Nano formulations of natural products for NDs treatment Several research attempted to identify phytochemicals having beneficial effects on the nervous system derived from medicinal or even nutritional plants. The majority of the therapeutic advantages of neuroprotective phytochemicals stem from the antioxidative properties of the substances in question.^[24] The bioavailability of natural bioactive ingredients in a frame is critical to their biological activity. It is most likely limited by the CNS's rapid metabolism, permeability, and lack of stability.²⁵

Role of phyto-nanomedicine on ND Treatment ND are primarily age-related illnesses that are becoming more common worldwide as the aged population grows. The actual problem, however is lack of efficient therapy rather than an increase in prevalence. According to published research, ND were discovered in the early 1900s, however, there are currently no viable treatments for these disorders in modern culture. A number of synthetic medications have showed promise in the treatment of various common NDs such as Autism, PD, AD, and other chronic disorders. The use of synthetic medications is accompanied with several negative effects, rendering them unsuitable for routine therapy. Phytochemicals have antioxidative, anticholinesterase, antiinflammatory, and anti-amyloid characteristics, making them a prospective agents.^26,27Given that present treatments appear to be insufficient for the aforementioned illnesses, scientists are investigating their options with plant-based medications employing nanotechnology methods. Nanotheranostics is one strategy that is gaining popularity within the scientific community on a global scale for the treatment of ND. It uses nanoparticles for the for both diagnosis and treatment. Chemical engineers have devised a revolutionary nanotheranostic device that uses tunable light to activate nanoparticles,allowing for new applications in the field.²⁸

The role of BBB and its impact on therapy feasibility The BBB is a physical barrier generated by endothelial cells (ECs) that maintains and regulates the flow of nutrients and other important elements to the brain, thereby protecting its integrity. The ECs are positioned on the outside and inner sides of the tightly packed tight junctions that touch the outer EC membranes and restrict easy passage of materials.²⁹The BBB regulates the flow of materials in and out of the brain, maintains ionic balance, and protects against the diffusion of circulation agents, neurotransmitters, xenobiotics, and other compounds that can harm the brain's integrity.³⁰ Among the key players found to regulate the functions of tight junctions are astrocytes and cyclic adenosine monophosphate. The BBB is severely compromised in brain illnesses and disorders, which causes uncontrolled molecular diffusion and further brain damage.³¹ Because the BBB blocks materials based on their size and solubility, most potential medications are unable to pass through because they don't fit the necessary requirements. One popular strategy used to increase drug transportation across the barrier is temporal disruption with focused ultrasound,³² albeit the mechanism involved and the effect of the technique on an already disturbed barrier have yet to be determined. Otherwise, the search for a non-disruptive strategy for drug delivery to the brain has been prioritized, and NPs have recently proven to be effective in this function.

Advantages of NPs for brain therapy NPs have small particle size that facilitates their penetration across the BBB. The main hurdles to treating brain diseases and disorders have been overcoming the BBB and the blood–cerebrospinal fluid (CSF) barrier. The efflux of materials across BBB is carefully mediated by P-gp; hence, its down regulation is implicated its down regulation is implicated with the progression of ND and tumor.³³ Inhibiting P-gp enhances drug penetration across the BBB, and nanoparticles, with lower toxicity, can improve the targeting and efficacy of conventional drugs, resulting in reduced brain toxicity compared to traditional therapies. In a recent study, treatment with polyethylene glycol (PEG)-modified silica (Si) NPs has been shown to increase the cytotoxicity of anticancer drug, 3N-cyclopropylmethyl-7-phenyl-pyrroloquinolinone as compared to free drug in an in vitro model.³⁴ Despite the reported potential of NPs, some of these chemicals, such as Si NPs, have been proven to be cytotoxic, with the effect regulated by particle porosity and size.³⁵ Aside from using particle sizes and shapes that are less hazardous, another way for improving the efficacy of NPs is to add PEG, also known as PEGylation.³⁶ NPs enhance the solubility and bioavailability of traditional medicines. Other characteristics that are important in evaluating the efficacy of a medicine are solubility and bioavailability. Solubility is the ability of the drug to dissolve, whereas bioavailability is the extent to which the drug can reach the systemic blood circulation and subsequently the targeted site.³⁷ Unlike solubility, drug bioavailability can be influenced by both drug and body factors. Some of these variables include age, sex, gut pH, genetics, medicine dosage, and formulation. Because both characteristics are so important, enhancing both of them can result in enhanced therapeutic efficacy and, ultimately, illness treatment. Specificity and biocompatibility of the medication ensure effective delivery to the targeted site. Incorporating drugs into NPs help to substantially enhance these parameters. Overall, the above data imply that NPs are highly specific and biocompatible and therefore can be used to deliver drugs to the targeted sites more efficiently.

The application of NPs in the treatment of brain diseases and disorders:

Brain Tumor Brain tumor can be both malignant and benign. Because of the complexity of the brain, not only the metastatic but also the growth of benign tumors might have negative consequences. According to the 2018 report, there were more than 298,000 new cases of brain tumor worldwide.³⁸ The progression of the disease is linked to cognitive impairment. The disease’s pathology is not fully understood, and therapy options remain questionable. Several studies, however, have revealed that nanoparticles offer a therapeutic benefit in delivering potential anticancer medicines.³⁹ Polymeric nanoparticles containing small interfering RNA that targets genes such as Na-K-Cl cotransporter and EGFR can effectively inhibit glioblastoma cell growth and migration. Modified nanoparticles containing herpes simplex virus thymidine kinase and ganciclovir reduce glioma cell viability and improve survival in tumor-bearing mice.⁴⁰ The results presented above confirms the use of NPs for gene and medication delivery to target brain cancers. Alzheimer's disease is a prevalent kind of dementia defined by aging-related neuronal degeneration, which results in decreased cognitive ability and other neuropathological characteristics.

Recent trends of phyto-Neuro medicine The latest advancements in the domains of green chemistry and nanotechnology are promising and indicate significant potential in the advancement of biomedical sciences from a theranostic perspective.⁴¹ However, this potential, has not been used to produce therapies for ND such as AD and PD. The use of chemically manufactured compounds has limits, such as toxicity and expense. Furthermore, a study found that several compounds utilized in the chemical production of NPs had a tendency to remain attached to the NP surface, rendering them unsuitable for biological applications. As a result, the attention has shifted to the creation of materials based on green chemistry and a green method. Traditionally, the green chemistry-based strategy has relied on the use of medicinal plants or phytochemicals in their purest form, as these phytochemicals provide chelation and stability to the NPs. Suganthy et al.⁴² found that biogenic AuNPs from Terminalia arjuna provide neuroprotection by inhibiting AChE, reducing Aβ fibrillation, and destabilizing mature fibrils. Trehalose-functionalized AuNPs showed improved protein aggregation inhibition and potential in photothermal therapy. Another method is to use biogenic platinum nanoparticles biosynthesized from Bacopa monnieri as a neuroprotectant. The functionalization of NPs with phytochemicals has produced considerable effects. Because of their reduced adverse effects and greater target specificity, phyto-nanomedicines hold significant promise for developing treatment options for ND.

Future nano therapeutics for ND Without a doubt, precision-based nanomedicine will gain more attention in the coming years. Despite advancement, the use of phages in humans is still not widely accepted. There is a gap that need to be filled between animal testing and human application. Approval from the Food and Drug Administration is necessory, and it is expected to come on the heels of increasingly promising phage-based nanomedicine studies. Exosomes, which are naturally produced by human cells, are emerging as a new generation of highly protective nanoplatforms for efficient drug delivery.⁴³ Exosomes, with their unique structure, are well-suited for delivering hydrophilic and lipophilic agents. Despite promising research, challenges include inadequate characterization, low yield, poor encapsulation efficiency, and limited purification methods. Advances in exosome molecular and nano engineering could revolutionize precision medicine for diseases like neurodegenerative disorders. Aptamer-mediated delivery is emerging as a cost-effective and efficient method for targeted exosomal delivery.⁴⁴Improving the predictive accuracy of preclinical studies is crucial for successful clinical trials. The Federal Interagency Traumatic Brain Injury Research (FITBIR) system facilitates shared TBI research to enhance this effort.⁴⁵ Future nanomaterial development for acute brain injuries will focus on precise pharmacokinetics, relevant animal models, multifactorial experimental design, and advanced biomarker measurement technologies.

Conclusion and future direction Nanotechnology enhances disease diagnosis and treatment by improving drug efficacy and equipment sensitivity, with nanoparticles (NPs) offering potential for brain disorders. However, their toxicity and bioaccumulation require careful study, emphasizing the need for low-toxicity NPs and targeted biomarker sensitivity to maximize therapeutic outcomes.

REFERENCES:

1. Moradi F, Dashti N. Targeting neuroinflammation by intranasal delivery of nanoparticles in neurological diseases: a comprehensive review. Naunyn-Schmiedeberg's Archives of Pharmacology. 2022; Feb; 395(2): 133-148. doi: https:doi.org/10.1007/s00210-021-02196-x

2. Rahman MM, Ferdous KS, Ahmed M. Emerging promise of nanoparticle based treatment for Parkinson’s disease. Biointerface Reserach in Applied Chemistry. 2020; 10: 7135–7151. doi:https://doi.org/10.33263/BRIAC106.71357151

3. Rauf A, Badoni H, Abu-Izneid T, Rahman MM. Neuroinflammatory Markers: Key Indicators in the Pathology of Neurodegenerative Diseases. Molecules. 2022; May 17; 27(10): 3194. doi: https://doi.org/10.3390/molecules27103194

4. Rahman MM, Ferdous KS, Ahmed M. Hutchinson-Gilford progeria syndrome: an overview of the molecular mechanism, Pathophysiology and disease. Current Medicinal Chemistry. 2016; Mar 1; 23(9): 929–952. doi: 10.2174/1566523221666210303100805

5. Mitra S, Lami MS, Ghosh A, Das R. Hormonal therapy for gynecological cancers: how far has science progressed toward clinical applications?. Cancers . 2022 Feb 1; 14(3): 759. doi: https://doi.org/10.3390/cancers14030759

6. Popovic N, Brundin P. Therapeutic potential of controlled drug delivery systems in neurodegenerative diseases. International Journal of Pharmaceutics. 2006; May 18; 314(2): 120–126. doi: https://doi.org/10.1016/j.ijpharm.2005.09.040

7. Singh N, Pillay V, Choonara YE. Advances in the treatment of Parkinson’s disease. Progress in Neurobiology. 2007; Jan 1; 81(1): 29–44. doi: https://doi.org/10.1016/j.pneurobio.2006.11.009

8. Tysnes, Storstein A. Epidemiology of Parkinson’s disease. Journal of Neural Transmission. 2017 Aug; 124:901–905. doi: https://doi.org/10.1007/s00702-017-1686-y

9. Calzoni E, Cesaretti A, Polchi A. Biocompatible polymer nanoparticles for drug delivery applications in cancer and neurodegenerative disorder therapies. Journal of Functional Biomaterials. 2019 Jan 8; 10(1): 4. doi: https://doi.org/10.3390/jfb10010004

10. Kim MH, Kim SH, Yang WM. Mechanisms of action of phytochemicals from medicinal herbs in the treatment of Alzheimerʼs disease. Planta Medica. 2014 Oct; 80(15): 1249–1258. doi: 10.1055/s-0034-1383038

11. Naoi M, Shamoto-Nagai M, Maruyama W. Neuroprotection of multifunctional phytochemicals as novel therapeutic strategy for neurodegenerative disorders: Antiapoptotic and antiamyloidogenic activities by modulation of cellular signal pathways. Future Neurology. 2019 Jan 25; 14(1): FNL9. doi: https://doi.org/10.2217/fnl-2018-0028

12. Abada E, Mashraqi A, Modafer Y. Review green synthesis of silver nanoparticles by using plant extracts and their antimicrobial activity. Saudi Journal of Biological Sciences. 2023; Nov 26; 103877. doi:https://doi.org/10.1016/j.sjbs.2023.103877

13. Martin-Banderas L, Holgado MA, Durán-Lobato M. Role of nanotechnology for enzyme replacement therapy in lysosomal diseases. A focus on Gaucher’s disease. Current Medicinal Chemistry. 2016 Mar 1; 23(9): 929–952.

14. Amarasinghe LD, Wickramarachchi PA, Aberathna AA. Comparative study on larvicidal activity of green synthesized silver nanoparticles and Annona glabra (Annonaceae) aqueous extract to control Aedes aegypti and Aedes albopictus (Diptera: Culicidae). Heliyon. 2020; Jun 1; 6(6).

15. Castillo-Henríquez L, Alfaro-Aguilar K, Ugalde-Alvarez J. Green synthesis of gold and silver nanoparticles from plant extracts and their possible applications as antimicrobial agents in the agricultural area. Nanomaterials. 2020; Sept 7; 10(9): 1763. doi: https://doi.org/10.3390/nano10091763

16. Jebril S, Jenana RK, Dridi C. Green synthesis of silver nanoparticles using Melia azedarach leaf extract and their antifungal activities: In vitro and in vivo. Materials Chemistry and Physics. 2020; Jul 1; 248: 122898. doi: https://doi.org/10.1016/j.matchemphys.2020.122898

17. Nath D, Banerjee P. Green nanotechnology–a new hope for medical biology. Environmental Toxicology and Pharmacology. 2013; Nov 1; 36(3): 997–1014. doi: https://doi.org/10.1016/j.etap.2013.09.002

18. Narayanan KB, Sakthivel N. Green synthesis of biogenic metal nanoparticles by terrestrial and aquatic phototrophic and heterotrophic eukaryotes and biocompatible agents. Advances in Colloid and Interface Science. 2011; Dec 12; 169(2): 59-79. doi: https://doi.org/10.1016/j.cis.2011.08.004

19. Rao KJ, Korumilli T, Jakkala S, Singh K. Optimization of the one-step green synthesis of silver and gold nanoparticles using aqueous Athyrium filix femina extract using the taguchi method. BioNanoScience. 2021; Dec; 11: 915-922. doi: https://doi.org/10.1007/s12668-021-00909-3

20. Abbott NJ, Patabendige AA, Dolman DE, Yusof SR. Structure and function of the blood–brain barrier. Neurobiology of Disease. 2010; Jan 1; 37(1): 13-25. doi: https://doi.org/10.1016/j.nbd.2009.07.030

21. Moghimi SM, Hunter AC, Murray JC. Nanomedicine: current status and future prospects. The FASEB Journal. 2005; Mar; 19(3): 311-330. doi: https://doi.org/10.1096/fj.04-2747rev

22. Kong SD, Lee J, Ramachandran S. Magnetic targeting of nanoparticles across the intact blood–brain barrier. Journal of Controlled Release. 2012; Nov 28; 164(1): 49-57. doi: https://doi.org/10.1016/j.jconrel.2012.09.021

23. Smith MW, Gumbleton M. Endocytosis at the blood–brain barrier: from basic understanding to drug delivery strategies. Journal of Drug Targeting. 2006; Jan 1; 14(4): 191-214. doi: https://doi.org/10.1080/10611860600650086

24. Rahman MM, Islam MR, Shohag S, Hossain ME. The multifunctional role of herbal products in the management of diabetes and obesity: a comprehensive review. Molecules. 2022; Mar 6; 27(5): 1713. doi: https://doi.org/10.3390/molecules27051713

25. Bengmark S. Curcumin, An atoxic antioxidant and natural NfkB, cyclooxygenase-2, lipooxygenase, and inducible nitric oxide synthase inhibitor: A shield against acute and chronic diseases. Journal of Parenteral and Enteral Nutrition. 2006; Jan; 30(1): 45-51. doi:https://doi.org/10.1177/014860710603000145

26. Xu J, Wold EA, Ding Y, Shen Q. Therapeutic potential of oridonin and its analogs: from anticancer and antiinflammation to neuroprotection. Molecules. 2018; Feb 22; 23(2): 474. doi: https://doi.org/10.3390/molecules23020474

27. Hajialyani M, Hosein Farzaei M, Echeverría J. Hesperidin as a neuroprotective agent: a review of animal and clinical evidence. Molecules. 2019; Feb 12; 24(3): 648. doi: https://doi.org/10.3390/molecules24030648

28. Lausanne EP. On the Way to Nanotheranostics: Diagnosing and Treating Diseases Simultaneously. 2021; May 15.

29. Reese TS, Karnovsky MJ. Fine structural localization of a blood-brain barrier to exogenous peroxidase. The Journal of Cell Biology. 1967; Jul 1; 34(1): 207-217. doi: 10.1083/jcb.34.1.207.

30. Abbott NJ, Patabendige AA, Dolman DE, Yusof SR. Structure and function of the blood–brain barrier. Neurobiology of Disease. 2010; Jan 1; 37(1): 13-25. doi: 10.1016/j.nbd.2009.07.030.

31. Dallasta LM, Pisarov LA, Esplen JE . Blood-brain barrier tight junction disruption in human immunodeficiency virus-1 encephalitis. The American Journal of Pathology. 1999; Dec 1; 155(6): 1915-1927. doi:10.1016/S0002-9440(10)65511-3

32. McDannold N, Arvanitis CD, Vykhodtseva N, Livingstone MS. Temporary disruption of the blood–brain barrier by use of ultrasound and microbubbles: safety and efficacy evaluation in rhesus macaques. Cancer Research. 2012; Jul 15; 72(14): 3652-3663. doi: 10.1158/0008-5472.CAN-12-0128

33. Henson JW, Cordon-Cardo C, Posner JB. P-glycoprotein expression in brain tumors. Journal of Neuro-oncology. 1992; Sep; 14: 37-43. doi:10.1007/BF00170943

34. Morillas-Becerril L, Peta E, Gabrielli L, Russo V. Multifunctional, CD44v6-targeted ORMOSIL nanoparticles enhance drugs toxicity in cancer cells. Nanomaterials. 2020; Feb 10; 10(2): 298. doi:10.3390/nano10020298

35. Mohammadpour R, Yazdimamaghani M, Cheney DL, Jedrzkiewicz J. Subchronic toxicity of silica nanoparticles as a function of size and porosity. Journal of Controlled Release. 2019; Jun 28; 304: 216-232. doi: 10.1016/j.jconrel.2019.04.041

36. Mendonça MC, Soares ES, de Jesus MB. PEGylation of reduced graphene oxide induces toxicity in cells of the blood–brain barrier: an in vitro and in vivo study. Molecular Pharmaceutics. 2016; Nov7; 13(11): 3913-3924. doi:10.1021/acs.molpharmaceut.6b00696

37. Chow SC. Bioavailability and bioequivalence in drug development. Wiley Interdisciplinary Reviews: Computational Statistics. 2014; Jul; 6(4): 304-312. doi: https://doi.org/10.1002/wics.1310

38. Bray F, Ferlay J, Soerjomataram I, Siegel RL. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a Cancer Journal for Clinicians. 2018; Nov; 68(6): 394-424. doi: https:// doi.org/10.3322/caac.21492

39. Nance E, Zhang C, Shih TY. Brain-penetrating nanoparticles improve paclitaxel efficacy in malignant glioma following local administration. ACS nano. 2014 Oct 28;8(10):10655-10664.

40. Mangraviti A, Tzeng SY, Kozielski KL. Polymeric nanoparticles for nonviral gene therapy extend brain tumor survival in vivo. ACS Nano. 2015; Feb 24; 9(2): 1236-1249.

41. Khalil AT, Ovais M, Ullah I. Sageretia thea (Osbeck.) mediated synthesis of zinc oxide nanoparticles and its biological applications. Nanomedicine. 2017; Aug 1; 12(15): 1767-1789. doi: https://doi.org/10.2217/nnm-2017-0124

42. Suganthy N, Sri Ramkumar V, Pugazhendhi A. Biogenic synthesis of gold nanoparticles from Terminalia arjuna bark extract: assessment of safety aspects and neuroprotective potential via antioxidant, anticholinesterase, and antiamyloidogenic effects. Environmental Science and Pollution Research. 2018; Apr; 25: 10418-10433. doi: https://doi.org/10.1007/s11356-017-9789-4

43. Soliman HM, Ghonaim GA, Gharib SM, Chopra H. Exosomes in Alzheimer’s disease: from being pathological players to potential diagnostics and therapeutics. International Journal of Molecular Sciences. 2021; Oct 6; 22(19): 10794. doi: https://doi.org/10.3390/ijms221910794

44. Tran PH, Xiang D, Tran TT. Exosomes and nanoengineering: a match made for precision therapeutics. Advanced Materials. 2020; May; 32(18): 1904040. doi: https://doi.org/10.1002/adma.201904040

45. Kandell RM, Waggoner LE, Kwon EJ. Nanomedicine for acute brain injuries: insight from decades of cancer nanomedicine. Molecular Pharmaceutics. 2020; Jun 25; 18(2): 522-538.

Received on 31.07.2024 Revised on 18.11.2024

Accepted on 23.01.2025 Published on 01.07.2025

Available online from July 05, 2025

Research J. Pharmacy and Technology. 2025;18(7):3453-3459.

DOI: 10.52711/0974-360X.2025.00497

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.