Brain specific delivery Application ..pptx

Brain-specific drug delivery systems (BDDS) are cutting-edge technologies created to efficiently deliver therapeutic agents to the brain, circumventing the obstacles presented by the blood-brain barrier (BBB), a defense mechanism that restricts the entry of the majority of medications into the brain. The BBB ensures that harmful substances do not reach the brain but also restricts the entry of many potentially beneficial drugs. To address this issue, brain-specific drug delivery systems have emerged as a promising strategy for the treatment of various neurological conditions, such as Alzheimer’s disease, Parkinson’s disease, brain tumors, stroke, and multiple sclerosis.

1. APPLICATION OF BRAIN SPECIFIC DELIVERY NAME:-VIMAL PATHAK COURSE:- M PHARM 2 ND SEM ROLL NO :-2407401007 DEPARTMENT OF PHARMACEUTICS PRESENTED TO: Dr. Amit lather Geeta institute of pharmacy Geeta university Panipat

2. Contents : Application of brain specific drug delivery. Treatment of neurodegenerative diseases. Brain cancer therapy. Mental health disorder. Recent advancement.

3. 1. Treatment of Neurodegenerative Diseases: Alzheimer’s disease: Alzheimer’s disease (AD) is characterized by the accumulation of amyloid plaques and neurofibrillary tangles, leading to cognitive decline. Traditional drug delivery approaches often fail to cross the BBB efficiently. RECENT ADVANCEMENT: Lecanemab and Donanemab both drugs target amyloid plaques. Amyloid plaques are abnormal protein deposits found in the brain of people with Alzheimer's disease.

4. Conti… Nanoparticles and liposomes can be engineered to encapsulate these drugs, enhancing their delivery across the BBB and directly targeting affected regions of the brain, there by improving therapeutic outcomes.

5. I. Symptomatic Therapy: Symptomatic therapy focuses on managing the symptoms of Alzheimer's disease and Parkinson's disease .Main aim to improve cognitive function( Think,Learn ,remember.) Dopamine deficiency in the striatum of PD patients was first reported in the 1960s, and levodopa was developed as a drug that improves both the symptoms and life prognosis of patients . This drug is still the gold standard for treating PD. However, by the mid-1970s, it became apparent that motor complications, such as a wearing-off phenomenon, appear after using levodopa for several years . 

6. Problems with current levodopa treatment: Levodopa is the most reliable anti-pd drug for improvement of motor symptoms. However, the half-life of levodopa in blood is short (about 90 minutes), which causes fluctuations in blood levels that result in changes in clinical symptoms in the advanced stage, manifesting as the wearing-off phenomenon. Thus, the development of levodopa therapy with a longer half-life using a different route of administration or formulation is being examined.

7. 2.Brain Cancer Therapy: Glioblastoma multiforme (GBM): GBM is a highly aggressive form of brain cancer that is difficult to treat due to the inability of many chemotherapeutic agents to cross the BBB. (Glial cells) Nanoparticle-based delivery systems offer a promising approach for overcoming the BBB. These carriers can also be functionalized with targeting ligands (e.g., Antibodies or peptides) that specifically bind to tumor cells, ensuring that the drug is delivered only to the cancerous tissue while minimizing damage to healthy tissue.

8. Recent Advancements in Glioblastoma Treatment: 1)CAR-T cell therapy: A clinical trial showed dramatic and rapid tumor regression in some glioblastoma patients using a next-generation CAR-T therapy. This approach genetically modifies the patient's t-cells to specifically target and attack cancer cells. (Mass general) 2)Tumor Treating Fields (TTFields) Therapy: TTFields therapy uses electrical fields to disrupt cancer cell division. This method has been found to extend survival and maintain a better quality of life in glioblastoma patients.

9. 3.Mental Health Disorders: Schizophrenia and depression: Mental health disorders often require drugs like antipsychotics or antidepressants to be delivered to specific regions of the brain (e.g., The prefrontal cortex or limbic system). Recent advancement: Cobenfy ( karxt ):  A new medication approved in September 2024, uses a different mechanism of action than previous drugs for schizophrenia.  Pimavanserin (nuplazid):  an inverse agonist/antagonist at 5-ht2a receptors, used to treat psychosis in patients with parkinson's disease.  Lumateperone ( caplyta ):  a newer antipsychotic medication. 

10. Cobenfy mode of action: Unlike traditional antipsychotic drugs that primarily target dopamine receptors, Cobenfy combines two components: Xanomeline: A muscarinic receptor agonist that activates specific cholinergic receptors in the brain, which are crucial for memory and cognitive functions. Trospium chloride : A muscarinic receptor antagonist that does not significantly cross the blood-brain barrier, acting mainly in peripheral tissues to mitigate potential side effects associated with Xanomeline. This combination allows Cobenfy to alleviate psychotic symptoms without the common side effects linked to dopamine-blocking drugs, such as drowsiness, weight gain, and muscle tremors.

11. Recent advancement : Nanotechnology: N anotechnology has revolutionized drug delivery by enabling the creation of nanoparticles that can cross the BBB more effectively than larger molecules. Polymer-based nanoparticles: These versatile carriers can encapsulate therapeutic agents, allowing for targeted delivery and sustained release at the disease site. For instance, PLGA (poly(lactic-co-glycolic acid) nanoparticles have shown promise in delivering neuroprotective drugs for conditions such as Alzheimer's disease. Gold nanoparticles: research has indicated that gold nanoparticles can effectively transport drugs across the BBB while providing antioxidant effects that may be beneficial in treating neurodegenerative diseases.

12. Scaffolds for brain drug delivery: Scaffolds are implantable and can be used to treat a variety of conditions associated with brain injury and diseases, for delivering drugs to treat neurological diseases such as Parkinson's disease and Alzheimer's disease. Worley S et al. Studied efficacy of poly (hydroxyl phenyl methacrylate) [PHPMA] and PHEMA scaffolds containing glucosamine or n-acetyl glucosamine groups when implanted between the septum and the hippocampus in a fimbria-fornix lesion cavity. It was found that[ PHEMA ]scaffolds showed markedly less infiltration of connective tissue than [PHEMA].

13. Reference: 1)Bummer PM, physical chemical considerations of lipid based oral drug delivery, solid lipid nanoparticles, critical review, therapeutic drug carrier system, 2004; 21 (2) 1-20. 2. Shrikant CS, mahale NB, Chaudhari SR, throat RS, recent advances in brain targeted drug delivery system: a review, 2015; 4(5): 542-559. 3. Ganesh S, Sahiwal A, Shrenik P, drug delivery to the central nervous system: a review, received 16 June 2003, revised 26 June 2003. 4. Bickel U, how to measure drug transport across the blood brain barrier, 2005