Formulation, Development, and In Vitro Evaluation of a CD22 Targeted Liposomal System Containing a Non-Cardiotoxic...

Area of Science:

• * Nanomedicine and Drug Delivery
• * Cancer Therapeutics
• * Molecular Biology

Background:

• * Doxorubicin-induced cardiotoxicity necessitates improved chemotherapeutic agents like AD 198.
• * Current AD 198 therapy can cause depletion of healthy neutrophils and thrombocytes.
• * Targeted drug delivery systems are crucial for enhancing AD 198 efficacy and safety.

Purpose of the Study:

• * To develop and analyze targeted liposomes encapsulating AD 198 for cancer therapy.
• * To optimize liposomal formulations for physicochemical properties and drug release.
• * To evaluate the targeted delivery and in vitro efficacy of AD 198-loaded liposomes.

Main Methods:

• * Liposome formulation and optimization using selected lipids.
• * Characterization of liposomes for size, zeta-potential, and dissolution.
• * Conjugation of anti-CD22 Fab' for active targeting to CD22-positive cells.
• * In vitro cytotoxicity assays using CD22-positive (Daudi) and CD22-negative (Jurkat) cell lines.
• * Investigation of cellular uptake pathways and intracellular localization.

Main Results:

• * Optimized liposomes exhibited sizes between 115-145 nm and zeta-potentials of -8 to -15 mV.
• * Approximately 30% of AD 198 was released from liposomes over 72 hours.
• * Targeted liposomes demonstrated significantly higher cytotoxicity in CD22+ve Daudi cells compared to CD22-ve Jurkat cells.
• * Cellular uptake occurred via a clathrin- and caveolin-independent pathway, with endolysosomal localization.
• * Apoptotic pathways, including caspase-3 and c-myc regulation, were activated upon drug release.

Conclusions:

• * CD22-targeted liposomes effectively deliver AD 198 to malignant cells.
• * This targeted approach enhances potency and specificity compared to untargeted formulations.
• * The developed liposomal system offers a promising strategy to mitigate AD 198 side effects and improve cancer treatment.