SCDT-50. SURFACE MODIFIED LIPOSOMES FOR EFFECTIVE DELIVERY OF THERAPEUTIC AGENTS ACROSS THE BLOOD BRAIN BARRIER
Bibliographic record
Abstract
Liposomes are lipid bilayer nanovesicles that have inherent ability to deliver therapeutic and imaging agents to the tumor cells due to enhanced permeability and retention effect (EPR effect) and also by active targeting mechanism. The major hurdles in delivering the therapeutic agents to CNS malignancies are the blood-brain and blood-tumor barriers. Although several drugs are known to cross the blood brain barrier (BBB), they are not effective in eliminating the tumors completely. So a formulation that could enhance their ability to get across the BBB and actively targeting the tumor is necessary to overcome blood brain and blood tumor barrier. We have formulated variety of liposomes by varying the surface molecules and therapeutically active lipids. To determine the feasibility of the liposome formulation to cross the blood brain barrier we developed an in vitro blood brain barrier model using bovine brain microvascular endothelial cells (BBMVEC) cultured as monolayer. Various liposomal doxorubicin formulations were prepared after modifying their surface by protein conjugation, a small molecule inhibitor (farnesyl thiosalicylic acid), a small molecule iron chelator (Dp44mt) and glutathione. All the small molecules were chosen for this study rationally by in silico determination of the feasibility of the molecules to cross the BBB. Moreover, the liposomal doxorubicin was also rationally designed to mimimize the cardiotoxicity mediated by doxorubicin and to synergistically improve the therapeutic efficacy. In vitro cytotoxicity assays were performed in the glioma cell lines. BBB transport studies were performed after culturing bovine brain endothelial cells as monolayer in a transwell system. A time dependent increase in the transport of the compound occurs as evidenced by the in vitro BBB model. In vivo investigation reveals the transport of the targeted liposomes through the blood brain barrier after intravenous administration of the liposomes, as evidenced by fluorescent microscopic images of the mouse brain tissue.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".