Life Sciences & Biotechnology
Title : | Novel leukocyte-functionalized biomimetic lipid nanoparticles platform for spatial and temporal delivery of therapeutic agent to atherosclerotic plaques |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Gaurav Kumar Jain, Delhi Pharmaceutical Sciences And Research University, New Delhi |
Timeline Start Year : | 2022 |
Timeline End Year : | 2024 |
Contact info : | drgkjain@gmail.com |
Equipments : | Differential Scanning Colorimetry |
Details
Executive Summary : | Atherosclerosis is the predominant cause for stroke and myocardial infarction and atherosclerotic cardiovascular diseases (ACVDs) are the fore most cause of morbidity worldwide. The treatment of ACVDs is limited by delivery of therapeutic drug concentrations over prolong period at the atherosclerotic plaque and vasculature site. With the recent progress in molecular biology, it is evident that atherosclerosis is a chronic inflammatory disease convoyed by subendothelial accretion of fibro-inflammatory lipid plaque, and transendothelial migration of leukocytes in response to inflammation. Aim: The aim of the present proposal is to develop “Novel leukocyte-functionalized biomimetic lipid nanoparticles platform” for spatial (targeted) and temporal (sustained) delivery of therapeutic agents to atherosclerotic plaques by exploiting properties of both lipid nanoparticles and of leukocytes. Methodology: As a first step negatively charged lipid nanoparticles (LNPs) will be prepared by modification of our previously developed method. The LNPs will be evaluated for size, charge, morphology and crystallanity. The loading and release of pravastatin (hydrophilic), rapamycin (hydrophobic) and evolocumab (biologics) will be evaluated. The developed LNPs will be functionalized by ionic interaction with extracted leukocytes to form leukocyte-functionalized lipid nanoparticles (LLNPs). The LLNPs will be characterized for size, charge, crystallanity, and coating and orientation of leukocyte membrane. Cellular studies will be conducted to determine uptake and inhibition of cell proliferation followed by hemocompatibility studies. Preclinical assessment of targeting potential and efficacy will be evaluated in experimental atherosclerotic murine model using scintigraphy and atherosclerotic lesion study, respectively. Outcome: The dual approach will develop a platform technology for targeted and sustained delivery of parenteral drugs and biologicals to the atherosclerotic plaques and lesions thereby reducing dose related side effects, reducing dose frequency and improving patient compliance. |
Total Budget (INR): | 28,80,540 |
Organizations involved