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Soumya Saroj1, Akshaya Kana Veedu1, Chandrasekhar Reddy U1
1Department of Chemistry, Indian Institute of Technology Madras, Chennai, Tamil Nadu 600036, India.
ACS Applied Bio Materials
|May 23, 2025
Summary
Novel oxanorbornane-based lipids conjugated with ibuprofen form solid lipid particles for doxorubicin delivery. This formulation, AT3.3, demonstrates high drug entrapment, controlled release, and a favorable safety profile, offering potential in cancer therapy.
Area of Science:
- Materials Science
- Nanotechnology
- Drug Delivery
Background:
- Oxanorbornane-based lipids offer a novel platform for drug delivery systems.
- Conjugation of non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen can modify lipid properties.
- Doxorubicin (Dox) is a widely used chemotherapy agent with limitations in delivery and side effects.
Purpose of the Study:
- To synthesize and characterize ibuprofen-conjugated oxanorbornane-based lipids.
- To evaluate these lipids as carriers for doxorubicin (Dox) delivery.
- To assess the safety, efficacy, and cellular uptake of the Dox-loaded lipid formulation.
Main Methods:
- Synthesis and characterization of lipid conjugates using 2D-NMR, PXRD, AFM, SEM, DLS, and qNano.
- Formation and characterization of solid lipid particles (SLPs) using TEM.
- Drug loading via pH gradient and in vitro release studies.
- Cytotoxicity assays (NIH3T3 cells), hemolytic assays, flow cytometry (A549 cells), and confocal microscopy (NIH3T3 and A549 cells).
- Reactive oxygen species (ROS) induction studies in cardiomyocytes and A549 cells.
Main Results:
- Ibuprofen conjugation increased interlipid spacing and altered lipid packing.
- The formulation AT3.3 achieved ~90% Dox entrapment with controlled release (18% in 24h, 66% in 5 days).
- Lipids and AT3.3 formulation showed good safety profiles in cytotoxicity and hemolytic assays.
- AT3.3 induced similar cellular effects to free Dox (cell cycle arrest) but altered intracellular localization.
- AT3.3 demonstrated a protective effect against ROS in cardiomyocytes compared to free Dox.
Conclusions:
- Ibuprofen-conjugated oxanorbornane lipids effectively form SLPs for doxorubicin delivery.
- The AT3.3 formulation exhibits high drug entrapment, controlled release, and an improved safety profile.
- This novel carrier system alters Dox intracellular localization and offers potential cardioprotection.
- These findings highlight the potential of AT3.3 as a promising nanocarrier for doxorubicin chemotherapy.
