Life Sciences & Biotechnology
Title : | LRP engineered nanolipidic carriers as potential therapeutics for brain targeting in Wilson's disease |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Rahul sHukla, National Institute Of Pharmaceutical Education And Research (NIPER) Raebareli, Uttar Pradesh |
Timeline Start Year : | 2023 |
Timeline End Year : | 2025 |
Contact info : | rahul.shukla@niperraebareli.edu.in |
Details
Executive Summary : | Wilson's disease (WD) is a rare autosomal genetic recessive disorder characterized by dysfunctional copper accumulation and metabolism due to mutational changes in the ATP7B gene. It affects the liver and brain homeostasis, causing liver cirrhosis and parkinsonism, ataxia, chorea, and tremors in the brain. Current therapies for WD include D-penicillamine, Trientine hydrochloride, and zinc supplement. However, these drugs have paradoxical side effects, such as neurological deterioration due to the high rate of free copper pool in the systemic circulation. MiADMsA, a recently reported drug, is under phase II clinical trial for copper chelation ability. Nanoengineering approaches, such as encapsulation in suitable carriers, can facilitate brain delivery and prolong the half-life of chelating drugs. Liposomes, which incorporate both hydrophilic and hydrophobic moieties, offer a viable approach for delivering drugs in the brain. However, the blood-brain barrier (BBB) presents a major hurdle in delivering chelating drugs in the CNs due to tight intracellular junctions, P-gp protein, and other reflux proteins. The proposed proposal involves drug-loaded DsPE-PEG 2000 decorated Angiopep-2 liposomes fabrication, which aid in permeation across the BBB and impart lipophilicity to an encapsulated hydrophilic drug moiety. This targeted liposome-based targeting of the drug and minimizing exposure to peripheral organs will provide better efficacy and targeting of drugs. In vivo pharmacodynamic evaluation of the proposed lipidic vesicles in a copper-induced preclinical model will be conducted. |
Total Budget (INR): | 23,63,080 |
Organizations involved