Alzheimer's Disease and Advanced Drug Delivery Strategies

Bhupendra G. Prajapati is Professor in the Department of Pharmaceutics at Shree S.K. Patel College of Pharmaceutical Education and Research, Ganpat University, Gujarat, India. An alumnus of Hemchandracharya North Gujarat University (Doctorate) and M.S. University of Baroda (B.Pharm and M.Pharm), he has over 22 years of experience in academia, research, and industry. Dr. Prajapati has received numerous accolades, including the AICTE's Career Award for Young Teacher and the President Award for Staff Excellence in Research and Capacity Building from Ganpat University. With over 80 national and international publications, he has secured various research grants and holds multiple patents in NDDS. He has supervised numerous Ph.D. and PG research scholars and delivered over 50 expert talks globally. As an editor of 10 international books and contributor of 70 book chapters, his research focuses on lipid-based drug delivery and nanotech formulations. Dr. Prajapati is an active member of IPA, APTI, and CRSIC. Dr. Chellappan is presently affiliated to the International Medical University (IMU), Kuala Lumpur, Malaysia. He boasts more than 18 years of active teaching experience in the current profession. In 2009, he completed his PhD in Pharmaceutical Sciences, from the prestigious Manipal University, India. His major research area has been inflammation in biological systems. He has published more than 250 publications in reputed research journals with a cumulative impact factor of >600. In addition, he is a reviewer for several high impact journals and is on the editorial board of several reputed scientific journals. Dr. Kendre currently serving as Vice-Principal and head of the Department of Pharmaceutics at Rajarshi Shahu College of Pharmacy in Buldana, Maharashtra, India. He has more than 17 years of academic, research and industrial experience. He published more than 60 research articles. He published an Indian patent and a number of book chapters with reputable publishing houses.

Contributors
About the editors
Preface
Acknowledgments

1. Etiology, pathogenesis of Alzheimer’s disease and amyloid beta hypothesis
SARIKA MARUTI KAMBLE, KALPESH RAMDAS PATIL AND AMAN B. UPAGANLAWAR

1. Introduction
2. Etiology of Alzheimer’s disease
3. Pathogenesis of Alzheimer’s disease
4. Diagnosis of AD
5. Amyloid beta protein hypothesis
6. Consequences of amyloid beta (Ab) formation
7. Genetic factors responsible for the Alzheimer’s disease
References

2. Neuroinflammation in Alzheimer’s disease
MOHIT AGRAWAL, MANMOHAN SINGHAL, BHUPENDRA GOPALBHAI PRAJAPATI, HEMA CHAUDHARY, YASH JASORIA, BHAVNA KUMAR, MANDEEP KUMAR ARORA AND JAGANNATH SAHOO

1. Introduction
2. History of neuroinflammation in AD
3. The concept of neuroinflammation in AD
4. Neuroinflammation: Causes and consequences of Alzheimer’s disease
5. BBB integrity and neuroinflammation
6. Role of cellular players
7. Role of mediators and modulators in neuroinflammation
8. Role of intracellular signaling pathway
9. Genetic studies
10. Imaging of neuroinflammation in AD
11. Possible intervention of neuroinflammation in AD
12. Factors associated with neuroinflammation
13. Development of therapeutic potential
14. Conclusion
References

3. Recent updates in chemistry of Alzheimer’s: Synthetic molecules
DEEPAK K. LOKWANI, SANGITA R. CHAVAN, VINOD G. UGALE, PRAKASH N. KENDRE AND SHIRISH P. JAIN

1. Introduction
2. MTDL approach associated with following scaffold or structures
3. Conclusion
References

4. Blood brain barrier and its significance in drug delivery to brain in Alzheimer disease
DHWANI RANA, SAGAR SALAVE, DIGNESH KHUNT AND DERAJRAM BENIVAL

1. Introduction
2. Blood brain barrier
3. Current treatments for AD
4. Emerging therapies for AD
5. Nanotherapeutics for AD
6. Other approaches for crossing BBB
7. Conclusion and future perspective
References

5. Nose to brain delivery for the treatment of Alzheimer’s disease
DIGNESH KHUNT, SAGAR SALAVE, DHWANI RANA, DERAJRAM BENIVAL, BHAVIN GAYAKVAD AND BHUPENDRA GOPALBHAI PRAJAPATI

1. Introduction
2. The nose-to-brain (N2B) pathway
3. AZD and current treament
4. Development of N2B delivery for AZD
5. Approaches to modulation of N2B delivery in AZD
6. Advantages of N2B delivery for AZD
7. Conclusion and future directions
References

6. Amyloid cascade hypothesis, tau synthesis, and role of oxidative stress in AD
JIGAR VYAS, NENSI RAYTTHATHA AND BHUPENDRA GOPALBHAI PRAJAPATI

1. Introduction to the amyloid (amyloid-beta peptide)
2. Biogenesis of amyloid-beta
3. Amyloid cascade hypothesis (ACH)
4. Pros and cons of the ACH
5. Therapeutic targeting for amyloid-beta in Alzheimer’s pathogenesis
6. Tau protein
7. Role of oxidative stress in AD
8. Corelation of amyloid B protein, tau process, and oxidative stress in AD
References

7. New biologicals and biomaterials in the therapy of Alzheimer’s disease
VIPUL PRAJAPATI, SHRADDHA SHINDE, PRINCY SHRIVASTAV AND BHUPENDRA GOPALBHAI PRAJAPATI

1. Introduction
2. Potential target for Alzheimer’s disease therapy
3. Biologicals used in therapy of Alzheimer’s disease
4. Biomaterials used in therapy of Alzheimer’s disease
5. Nanoparticles in the therapy of Alzheimer’s disease
6. Metal nanoparticles for Alzheimer’s disease treatment
7. Other NPs
8. Systems based on biomaterials for mass production of therapeutic cells
9. Challenges of biomaterial-based drug delivery approach in Alzheimer’s disease
10. Conclusion
References

8. Roles of nano medicine in diagnosis of Alzheimer’s disease
MONA AMIT KAUSHAL, NIKITA A. PATEL, GAURAVI XAVIER AND BHUPENDRA GOPALBHAI PRAJAPATI

1. Introduction
2. Diagnostic tools for AD
3. Future perspective of nano medicine and their effectiveness
4. Conclusion and limitations
References

9. Nanotechnology-based delivery for CRISPR-Cas 9 cargo in Alzheimer’s disease
SHRUTI RAWAL, AKRUTI KHODAKIYA AND BHUPENDRA GOPALBHAI PRAJAPATI

1. Introduction
2. Genome editing by CRISPR-Cas system
3. Genome editing targets and scope of CRISPR-Cas 9 technology in Alzheimer’s disease
4. Barriers and challenges to CRISPR-Cas 9 delivery
5. Synergizing nano and CRISPR: Nanocarriermediated delivery
6. Conclusions and prospects
References

10. Liposomes as carrier for drug delivery in Alzheimer’s disease
RAVISH J. PATEL, AMIT A. PATEL, NIDHI TRIVEDI, VIDHI PANDYA, AMIT ALEXANDER, VIRAL PATEL, BHUPENDRA GOPALBHAI PRAJAPATI AND PUNIT B. PAREJIYA

1. Introduction
2. Liposomes as nanocarrier system for drug delivery
3. Liposome preparation materials and process
4. Modification of liposomes
5. Liposome’s potential as drug delivery for AD
6. Conclusion
Acknowledgment
References

11. PLGA mediated drug delivery for Alzheimer’s disease
TOSHA PANDYA, MANGESH KULKARNI, SHEETAL ACHARYA AND BHUPENDRA GOPALBHAI PRAJAPATI

1. Introduction
2. PLGA in Alzheimer’s disease
3. Applications of PLGA in treatment of AD
4. Animal models for testing AD targeted PLGA formulations
5. Patents
6. Conclusion and future prospective
References

12. Regulatory and ethical concerns in the use of nanomaterials
NAKSHEE MEHTA, SRISHTI SHETTY, BHUPENDRA GOPALBHAI PRAJAPATI AND SARITHA SHETTY

1. Introduction
2. Nanomaterials
3. Existing regulations on nanomaterials
4. Regulatory concerns involved with the use of nanomaterials
5. Nanomaterials in formulations and drug delivery systems to treat Alzheimer (AD)
6. Ethical concerns involved with the use of nanomaterials
7. Future challenges and policies
References

13. Symptoms and conventional treatments of Alzheimer’s disease
MEHUL R. CHORAWALA, AAYUSHI C. SHAH, AANSHI J. PANDYA, NIRJARI R. KOTHARI AND BHUPENDRA GOPALBHAI PRAJAPATI

1. Introduction
2. Recent neuropathological aspects
3. Clinical presentation
4. Conventional therapeutic approaches
5. Hardships faced by caregivers
6. Need of treatments although AD is incurable
7. Recent advances in AD treatments
8. Conclusion and outlooks
References

14. Dendrimers in the management of Alzheimer’s disease
CHETNA MODI, BHUPENDRA GOPALBHAI PRAJAPATI, SUDARSHAN SINGH, ADITYA SINGH AND SHUBHRAT MAHESHWARI

1. Introduction
2. Synthesis method of dendrimers
3. Types of dendrimers
4. Method of drug loading in dendrimers
5. Properties of dendrimers
6. Characterization of dendrimers
7. Animal models: In vitro and in vivo studies
8. Applications in treatment of Alzheimer’s disease
9. Clinical trials
10. Patents
11. Conclusion
References

15. Precision medicines for the treatment of Alzheimer’s disease
SANGAMESHWAR B. KANTHALE, PRAKASH N. KENDRE, SOMNATH K. VIBHUTE, SHIRISH P. JAIN AND SHRADHA S. TIWARI

1. Introduction
2. Background
3. Comprehensive risk determination
4. Intervention design
5. Methodology
6. System biology method for AD research
7. Role of genetics in precision medicine
8. Nanoparticles as precision medicines in AD
9. Discovery, development, and validation of pathophysiological biomarker candidates in AD
10. Challenges in AD risk reduction
11. Next step and future directions
12. Conclusion
References

16. Nanoformulations targeting Alzheimer’s disease
DEVESH KAPOOR, DEEPAK SHARMA, YASHWANT PATHAK, BHUPENDRA GOPALBHAI PRAJAPATI AND BHAVIK SATANI

1. Introduction
2. Overview of BBB and B-CSFB
3. Obstacles in drug delivery to BBB/B-CSF in ADs
4. Nanocarrier based nanoformulations to combat AD’s
5. Carbon dots (CDs)
6. Nanodiamonds (NDs)
7. Fullerene
8. Nanotubes
9. Conclusion
References

17. Lipid nanoparticles in targeting Alzheimer’s disease
PRAKASH N. KENDRE, AJINKYA POTE, RASIKA BHALKE, BHUPENDRA GOPALBHAI PRAJAPATI, SHIRISH P. JAIN AND DEVESH KAPOOR

1. Introduction
2. Different types of LNs used in AD
3. Lipids nanoparticles (LNs) and AD
4. Limitations of LNs in CNS diseases
5. Regulatory considerations of LNs
6. Future prospective and conclusion
References

18. Novel therapeutic approaches for targeting Alzheimer’s disease
AKRUTI KHODAKIYA, SUNITA CHAUDHARY, ANKIT CHAUDHARY AND BHUPENDRA GOPALBHAI PRAJAPATI

1. Alzheimer’s disease: Scope of new therapeutic approaches
2. FDA approved drugs for Alzheimer’s disease
3. Novel therapeutic approaches
4. Conclusion and future perspectives
References

19. Micro and nanoemulsion as drug carriers in Alzheimer’s disease
AMI PATEL, HIMANSHU PALIWAL, KRUTIKA SAWANT AND BHUPENDRA GOPALBHAI PRAJAPATI

1. Introduction
2. Microemulsion and nanoemulsion formulation
3. Physicochemical characterization of formulations
4. Applications, current research and patent landscape of microemulsions and nanoemulsion
5. Pharmacokinetics and pharmacodynamic of developed NE/ME for AD
6. Conclusion and future perspectives
References

20. Targeted nanotechnology-based formulations
ANGELA CHINASA ANI, STEPHEN CHIJIOKE EMENCHETA, KOSARACHI JENNIFER ORAH, AMAN B. UPAGANLAWAR, BHUPENDRA GOPALBHAI PRAJAPATI, CHUKWUKA KANAYO ORANU AND CHUKWUEMEZUE PRAISES ONYEKWE

1. Introduction
2. Nanomaterials
3. Targeted nanotechnology-based formulations (TNbF)
4. Applications of targeted nanoformulations
5. Concerns in the design and application of nanoformulations
6. Clinical data
7. Prospects in the design of targeted nanoformulation
8. Conclusion
References

21. Drug delivery for Alzheimer’s disease using nanotechnology: Challenges and advancements
BINDIYA CHAUHAN, SHIVANI PATEL, BHUPENDRA GOPALBHAI PRAJAPATI AND SUDARSHAN SINGH

1. Introduction
2. Drug delivery strategies for Alzheimer diseases
3. Alzheimer’s disease clinical requirement and drug delivery challenges
4. Nanomedicine as future aspect in treatment of Alzheimer diseases
5. Nonmicellar based formulation
6. Dendrimers
7. Nanogels
8. Alzheimer diseases treatment with lipid-based nanoparticles
9. Metallic nanoparticles
10. Nanoparticulate-chelation-based Alzheimer diseases therapy
11. Nanomedicine theranostics formulations
12. Protein-coated nanoparticles
13. Antibody decorated nanoparticles
14. Novel biomarkers used in diagnosis of Alzheimer diseases
15. Conclusion and future perspective
References

22. Current trends and updates in the treatment of Alzheimer’s disease
NISHA H. PARIKH, PALAK K. PARIKH, HETANSH J. RAO, KASHISH SHAH, BHAVARTH P. DAVE AND BHUPENDRA GOPALBHAI PRAJAPATI

1. Introduction
2. Pathophysiology and multifactorial nature of AD
3. Current treatment approaches for AD
4. Potential therapeutic strategies for AD
5. Conclusion and perspective
References

23. Pharmacokinetics and pharmacodynamics of various novel formulations targeting Alzheimer’s disease
ASHWINI GAWADE, SATISH POLSHETTIWAR, HETAL HINGALAJIA, BHUPENDRA GOPALBHAI PRAJAPATI AND ADITYA SINGH

1. Introduction
2. Alzheimer’s disease
3. Currently available drug molecules for the management for AD
4. Treatments for AD in the CNS: Clinical pharmacokinetics and pharmacodynamics
5. Nanoparticle delivery system for the management of AD and their PK PD
6. Conclusion
References

24. Microbubbles-based drug delivery for antiAlzheimer’s drugs
MEENAKSHI PATEL, BHUPENDRA GOPALBHAI PRAJAPATI AND M.R. YADAV

1. Introduction
2. Ultrasound mediated microbubble therapy to overcome BBB for treating Alzheimer’s patients
3. Drug loaded lipid based microbubbles for AD
4. In vitro cell models of BBB for AD and microbubble-mediated drug delivery
5. Clinical trials of microbubble-based drug delivery for treatment of AD
6. Challenges and toxicity concerns of microbubble-based drug delivery for AD
7. Future aspects and conclusion
References

25. Neurotoxicity with the use of nanomaterials
SACHIN P. BORIKAR, SHIRISH P. JAIN, DEEPALI N. TAPRE, DEBARSHI KAR MAHAPATRA, ASAVARI V. MAHAJAN, DIPAK S. SONAWANE AND PRAKASH N. KENDRE

1. Introduction
2. Toxicity associated with nanomaterials
3. Brain as nanoparticles target
4. Properties of nanoparticles that influence toxicities
5. Mechanisms of neurotoxicity
6. Mitochondrial dysfunction due to nanoparticles
7. DNA damage due to nanoparticles
8. Endocrine dysfunction due to nanoparticles
9. Conclusion
References

26. Combinatorial therapy in Alzheimer’s disease
MAHENDRA GIRI, PRAKASH N. KENDRE, RASIKA BHALKE, VISHAL PANDE, KALYANI AUTADE AND RAJASHRI SUMBE

1. Introduction
2. Diagnostic criteria for Alzheimer’s disease
3. Combinatorial treatment strategies for Alzheimer’s disease
4. On-going clinical trialon AD
5. Summary
References

Index