Alzheimer's Disease and Advanced Drug Delivery Strategies

Dr. Bhupendra Gopalbhai Prajapati is a Professor (Research Cadre) at Parul Institute of Pharmacy, Parul University, Gujarat, India. He is also acting as Adjunct Professor at Department of Industrial Pharmacy, Faculty of Pharmacy, Silpakorn University, Thailand. With over 22 years of experience in academia, research, and industry, he specializes in lipid-based formulations, nano/microparticulate drug delivery, and bioavailability enhancement. A recipient of several prestigious awards including the AICTE Young Teacher Award and Ganpat University's Staff Excellence honors, Dr. Prajapati has published over 350 research/review papers, and has contributed to more than 170 book chapters. He actively mentors Ph.D. and PG scholars and serves as editor or section editor for several international publications in pharmaceutical sciences. 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.

• ContributorsAbout the editorsPreface Acknowledgments1. Etiology, pathogenesis of Alzheimer’s disease and amyloid beta hypothesisSARIKA MARUTI KAMBLE, KALPESH RAMDAS PATIL AND AMAN B. UPAGANLAWAR1. 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 diseaseMOHIT AGRAWAL, MANMOHAN SINGHAL, BHUPENDRA GOPALBHAI PRAJAPATI, HEMA CHAUDHARY, YASH JASORIA, BHAVNA KUMAR, MANDEEP KUMAR ARORA AND JAGANNATH SAHOO1. Introduction2. 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 moleculesDEEPAK K. LOKWANI, SANGITA R. CHAVAN, VINOD G. UGALE, PRAKASH N. KENDRE AND SHIRISH P. JAIN1. Introduction2. MTDL approach associated with following scaffold or structures3. ConclusionReferences4. Blood brain barrier and its significance in drug delivery to brain in Alzheimer diseaseDHWANI RANA, SAGAR SALAVE, DIGNESH KHUNT AND DERAJRAM BENIVAL1. 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 References5. Nose to brain delivery for the treatment of Alzheimer’s diseaseDIGNESH KHUNT, SAGAR SALAVE, DHWANI RANA, DERAJRAM BENIVAL, BHAVIN GAYAKVAD AND BHUPENDRA GOPALBHAI PRAJAPATI1. 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 ADJIGAR VYAS, NENSI RAYTTHATHA AND BHUPENDRA GOPALBHAI PRAJAPATI1. 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 diseaseVIPUL PRAJAPATI, SHRADDHA SHINDE, PRINCY SHRIVASTAV AND BHUPENDRA GOPALBHAI PRAJAPATI1. Introduction2. Potential target for Alzheimer’s disease therapy3. Biologicals used in therapy of Alzheimer’s disease4. Biomaterials used in therapy of Alzheimer’s disease5. Nanoparticles in the therapy of Alzheimer’s disease 6. Metal nanoparticles for Alzheimer’s disease treatment7. Other NPs8. Systems based on biomaterials for mass production of therapeutic cells9. Challenges of biomaterial-based drug delivery approach in Alzheimer’s disease10. ConclusionReferences8. Roles of nano medicine in diagnosis of Alzheimer’s diseaseMONA AMIT KAUSHAL, NIKITA A. PATEL, GAURAVI XAVIER AND BHUPENDRA GOPALBHAI PRAJAPATI1. Introduction2. Diagnostic tools for AD3. Future perspective of nano medicine and their effectiveness4. Conclusion and limitationsReferences9. Nanotechnology-based delivery for CRISPR-Cas 9 cargo in Alzheimer’s diseaseSHRUTI RAWAL, AKRUTI KHODAKIYA AND BHUPENDRA GOPALBHAI PRAJAPATI1. Introduction 2. Genome editing by CRISPR-Cas system3. Genome editing targets and scope of CRISPR-Cas 9 technology in Alzheimer’s disease4. 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 diseaseRAVISH J. PATEL, AMIT A. PATEL, NIDHI TRIVEDI, VIDHI PANDYA, AMIT ALEXANDER, VIRAL PATEL, BHUPENDRA GOPALBHAI PRAJAPATI AND PUNIT B. PAREJIYA1. Introduction2. Liposomes as nanocarrier system for drug delivery 3. Liposome preparation materials and process 4. Modification of liposomes5. Liposome’s potential as drug delivery for AD6. ConclusionAcknowledgmentReferences11. PLGA mediated drug delivery for Alzheimer’s diseaseTOSHA PANDYA, MANGESH KULKARNI, SHEETAL ACHARYA AND BHUPENDRA GOPALBHAI PRAJAPATI1. Introduction2. PLGA in Alzheimer’s disease3. Applications of PLGA in treatment of AD4. Animal models for testing AD targeted PLGA formulations5. Patents6. Conclusion and future prospectiveReferences12. Regulatory and ethical concerns in the use of nanomaterialsNAKSHEE MEHTA, SRISHTI SHETTY, BHUPENDRA GOPALBHAI PRAJAPATI AND SARITHA SHETTY1. Introduction2. Nanomaterials3. Existing regulations on nanomaterials4. Regulatory concerns involved with the use of nanomaterials5. Nanomaterials in formulations and drug delivery systems to treat Alzheimer (AD)6. Ethical concerns involved with the use of nanomaterials7. Future challenges and policiesReferences13. Symptoms and conventional treatments of Alzheimer’s diseaseMEHUL R. CHORAWALA, AAYUSHI C. SHAH, AANSHI J. PANDYA, NIRJARI R. KOTHARI AND BHUPENDRA GOPALBHAI PRAJAPATI1. Introduction2. Recent neuropathological aspects3. Clinical presentation4. Conventional therapeutic approaches5. Hardships faced by caregivers6. Need of treatments although AD is incurable7. Recent advances in AD treatments8. Conclusion and outlooksReferences14. Dendrimers in the management of Alzheimer’s diseaseCHETNA MODI, BHUPENDRA GOPALBHAI PRAJAPATI, SUDARSHAN SINGH, ADITYA SINGH AND SHUBHRAT MAHESHWARI1. Introduction2. Synthesis method of dendrimers3. Types of dendrimers4. Method of drug loading in dendrimers5. Properties of dendrimers6. Characterization of dendrimers7. Animal models: In vitro and in vivo studies8. Applications in treatment of Alzheimer’s disease9. Clinical trials 10. Patents 11. Conclusion References 15. Precision medicines for the treatment of Alzheimer’s diseaseSANGAMESHWAR B. KANTHALE, PRAKASH N. KENDRE, SOMNATH K. VIBHUTE, SHIRISH P. JAIN AND SHRADHA S. TIWARI1. 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 diseaseDEVESH KAPOOR, DEEPAK SHARMA, YASHWANT PATHAK, BHUPENDRA GOPALBHAI PRAJAPATI AND BHAVIK SATANI1. 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 References17. Lipid nanoparticles in targeting Alzheimer’s diseasePRAKASH N. KENDRE, AJINKYA POTE, RASIKA BHALKE, BHUPENDRA GOPALBHAI PRAJAPATI, SHIRISH P. JAIN AND DEVESH KAPOOR1. Introduction 2. Different types of LNs used in AD3. Lipids nanoparticles (LNs) and AD 4. Limitations of LNs in CNS diseases5. Regulatory considerations of LNs 6. Future prospective and conclusion References18. Novel therapeutic approaches for targeting Alzheimer’s diseaseAKRUTI KHODAKIYA, SUNITA CHAUDHARY, ANKIT CHAUDHARY AND BHUPENDRA GOPALBHAI PRAJAPATI1. Alzheimer’s disease: Scope of new therapeutic approaches2. FDA approved drugs for Alzheimer’s disease3. Novel therapeutic approaches4. Conclusion and future perspectivesReferences19. Micro and nanoemulsion as drug carriers in Alzheimer’s diseaseAMI PATEL, HIMANSHU PALIWAL, KRUTIKA SAWANT AND BHUPENDRA GOPALBHAI PRAJAPATI1. Introduction 2. Microemulsion and nanoemulsion formulation 3. Physicochemical characterization of formulations4. Applications, current research and patent landscape of microemulsions and nanoemulsion5. Pharmacokinetics and pharmacodynamic of developed NE/ME for AD 6. Conclusion and future perspectives References20. Targeted nanotechnology-based formulationsANGELA CHINASA ANI, STEPHEN CHIJIOKE EMENCHETA, KOSARACHI JENNIFER ORAH, AMAN B. UPAGANLAWAR, BHUPENDRA GOPALBHAI PRAJAPATI, CHUKWUKA KANAYO ORANU AND CHUKWUEMEZUE PRAISES ONYEKWE1. Introduction 2. Nanomaterials 3. Targeted nanotechnology-based formulations (TNbF) 4. Applications of targeted nanoformulations5. Concerns in the design and application of nanoformulations 6. Clinical data7. Prospects in the design of targeted nanoformulation8. ConclusionReferences21. Drug delivery for Alzheimer’s disease using nanotechnology: Challenges and advancementsBINDIYA CHAUHAN, SHIVANI PATEL, BHUPENDRA GOPALBHAI PRAJAPATI AND SUDARSHAN SINGH1. 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 diseaseNISHA H. PARIKH, PALAK K. PARIKH, HETANSH J. RAO, KASHISH SHAH, BHAVARTH P. DAVE AND BHUPENDRA GOPALBHAI PRAJAPATI1. Introduction2. 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 diseaseASHWINI GAWADE, SATISH POLSHETTIWAR, HETAL HINGALAJIA, BHUPENDRA GOPALBHAI PRAJAPATI AND ADITYA SINGH1. Introduction2. Alzheimer’s disease3. Currently available drug molecules for the management for AD4. Treatments for AD in the CNS: Clinical pharmacokinetics and pharmacodynamics5. Nanoparticle delivery system for the management of AD and their PK PD6. ConclusionReferences24. Microbubbles-based drug delivery for antiAlzheimer’s drugsMEENAKSHI PATEL, BHUPENDRA GOPALBHAI PRAJAPATI AND M.R. YADAV1. Introduction2. Ultrasound mediated microbubble therapy to overcome BBB for treating Alzheimer’s patients3. Drug loaded lipid based microbubbles for AD4. In vitro cell models of BBB for AD and microbubble-mediated drug delivery5. Clinical trials of microbubble-based drug delivery for treatment of AD6. Challenges and toxicity concerns of microbubble-based drug delivery for AD7. Future aspects and conclusionReferences25. Neurotoxicity with the use of nanomaterialsSACHIN P. BORIKAR, SHIRISH P. JAIN, DEEPALI N. TAPRE, DEBARSHI KAR MAHAPATRA, ASAVARI V. MAHAJAN, DIPAK S. SONAWANE AND PRAKASH N. KENDRE1. 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 diseaseMAHENDRA GIRI, PRAKASH N. KENDRE, RASIKA BHALKE, VISHAL PANDE, KALYANI AUTADE AND RAJASHRI SUMBE1. Introduction2. Diagnostic criteria for Alzheimer’s disease 3. Combinatorial treatment strategies for Alzheimer’s disease4. On-going clinical trialon AD 5. Summary References Index