How does nanotechnology play a role?

2. How does nanotechnology play a role?

6. Nanotechnology • Nanotechnology refers to the measurement and modeling of substances in a nanoscale manner, which can be applied to engineering and technology by modifying material materials to give them new properties. In current medical research, new diagnostic and therapeutic tools were developed combined with nanotechnology, which are beneficial to the specific transport and absorption of drugs and contrast agents to the brain and promote the regeneration of damaged neurons to limit or reverse neurological disorder.

7. Nanotechnology • Through nanotechnology, the controllable production of desired structures and devices with, at least, one dimension in nanoscale (1 • 100 nm) is presently achievable. • Nanotechnology is advancing molecular detection, drug discovery, delivery and monitoring for a number of ever challenging human diseases, including cancer and neurodegenerative disorders

8. Nanotechnology • the role of nanotechnology in the development and improvement of techniques for early diagnosis and effective treatment of Alzheimer’s disease (AD).

9. The overall goal of nanomedicine is to diagnose as accurately and early as possible, to treat as effectively as possible with minimal side effects, and to evaluate the efficacy of treatment

11. How does nanotechnology play a role?

12. Nanotechnology • present the role of nanotechnology in the development and improvement of techniques for early diagnosis and effective treatment of Alzheimer’s disease (AD). Since AD pathology is almost irreversible and present day medications for AD only lower its associated symptoms, application of disease modifying treatments could be successful only if AD early diagnosis is possible

13. Use of Nanotechnology • Detection of biomarkers(Diagnosis) • Drug Delivery(Treatment )

14. Nanotechnologies for detection of AD biomarkers in biological fluids • The development of effective treatments for neuronal degeneration will depend on early-diagnosis methods based on the detection and quantification of soluble AD biomarkers. • In practice, two approaches are available: • (1) The measurement of total τ protein and Aβ concentrations in cerebrospinal fluid(CSF) or plasma, and • (2) The detection of suspected pathogenic biomarkers, such as the hyperphosphorylatedτprotein and the Aβ

15. Nanotechnology-based Treatments for Alzheimer's Disease • The currently available therapeutics for AD, only act to lower its symptoms. In recent years, however, significant amount of research have been focused on finding the so called "neuroprotective agents", therapeutics that could stop the disease progress by targeting special molecular mechanisms in the AD pathology process. • However, more futuristic are approaches that could rebuild the damaged tissue, called as "regenerative agents". These two (neuroprotectiveand neuroregenerative) approaches together are known as "disease modifying approaches".

16. The therapeutic potential of nanotechnology for AD • The therapeutic potential of nanotechnology for AD includes both • 1-Neuroprotective and • 2-Neuroregenerative approaches

17. 1. Nanotechnology Neuroprotective Potentials • The main two sources of neurotoxicity in AD pathogenesis are: • 1- Aβoligomers • 2-free radicals . • Some of the nanotechnology-based approaches are capable of protecting neurons from Aβ toxicity by preventing from amyloidoligomerization . • The other nanotechnology neuroprotective approaches include those that protect neurons from oxidative stress of free radicals

18. Nanotechnology in the Treatment of AD • Conventional drug delivery including powder, capsule, tablet or liquid have crucial limitations including a high-dose requirement, low bioavailability, rapid first pass metabolism, and poor-pharmacokinetics • Indeed, some bioactive candidates, such as polyphenols, proteins, and peptides, were documented to be poorly soluble and less absorbed in gastrointestinal systems, and this accounts for their weak therapeutic efficacy in biological systems and associated failure in clinical trials

19. Nanotechnology in the Treatment of AD • Blood-brain barrier (BBB) is the primary barrier to the delivery of therapeutic drugs to the brain. Some treatments have forced them to open by causing structural damage to the BBB, at which point the BBB has lost its selectivity for drug passage. The carrier system combined with nanotechnology is the most promising treatment strategy for delivering drugs to the brain through the BBB.

22. NPs overcome these hurdles by safely transporting the drug across the acidic biological milieu with improved permeability, thereby delivering maximum efficacy at a relatively lower dose. • In addition, due to their malleable physicochemical properties, even a poorly soluble drug candidate can also be effectively translocated to the targeted site with an improved pharmacokinetic/bioavailability

24. Nanoparticles in drug delivery system and its importance • Nanoparticles (NP) are colloidal elements incorporated with active drug candidates, and these are considered to be a single entity that expresses controlled release/site-specific drug delivery in biological systems

25. Goal of nanotechnology • The overall goal of nanomedicine is to diagnose as accurately and early as possible, to treat as effectively as possible with minimal side effects, and to evaluate the efficacy of treatment noninvasively

26. Nanotechnology Improves Alzheimer’s Disease Drug Delivery • The effective treatment of Alzheimer’s disease has been relatively stunted, with most drugs only treating symptoms with relatively low success. Advancements in biomaterials and regenerative medicine technologies are offering novel ways of improving drug delivery to affected regions of the brain with a controlled release of drugs.

27. A research group  have used biomaterials in the form of nanoparticles, to optimise the treatment of Alzheimer’s disease. The team have encapsulated a licensed Alzheimer’s drug, memantine, in a biodegradable nanoparticle. • The nanoparticle acts as a vehicle for drug delivery, with a poly-ethylene glycol (PEG) coated surface which is effectively a chemical pass code for the blood-brain barrier, allowing for the nanoparticle – with drug encapsulated within – to enter the brain.

28. Nanoparticles in drug delivery system and its importance • Nanoparticles (NP) are colloidal elements incorporated with active drug candidates, and these are considered to be a single entity that expresses controlled release/site-specific • drug delivery in biological systems

29. Figure 3. Potential mechanism of action adapted by various nanoparticles-mediated drug delivery to the targeted site of action associated with AD – nanotherapeutics: • (a) anti-Ab – functionalized NPs involves in solubilization and clearance of Ab fibrils/aggregates, (b)AChE inhibitors loaded NPs targeting cholinergic system • impairment, (c) Antioxidants loaded NPs targeting oxidative stress milieu, (d)Proteasomes loaded NPs targeting hyper-phosphorylated tau proteins, (e) anti-Ab • loaded circulating NPs initiate ‘sink mechanism’ – by captivating the Ab fibrils from the brain to the effluence blood circulation. AChE: Acetylcholinesterase; Ab-: • amyloid beta fragment.

31. Thank you