Formulation And In Vitro And In Vivo Evaluation Of Ligand Functionalized Liposomes For Targeted Cancer Therapy

The traditional chemotherapy has weaknesses on non-specific biodistribution, severe systemic toxicity, and
optimum tumor accumulation. In a bid to overcome these obstacles, the present research was aimed at
developing and in vitro assessing PEGylated liposomes as a core system to target cancer therapy, where
Irinotecan hydrochloride, a prototype chemotherapeutic agent, was used in the study. The liposomes were
prepared successfully through the thin-film hydration and sonication technique using egg phosphatidylcholine,
cholesterol and methylated polyethylene glycol (MPEG). The prepared vesicles had ideal nanoscale properties
with a mean particle size of 152.3 ± 4.7 nm, polydispersity index of 0.18 ± 0.02, and zeta potential of -12.5 ±1.8
mV that are favorable to passive tumor targeting through Enhanced Permeability and Retention (EPR) effect.
Efficiency of drug entrapment of 85.4 ± 2.1 percent was attained. The in vitro drug release studies indicated a
sustained profile of up to 48 hours and stability studies showed that storage at 4degC was essential to the
maintenance of integrity of formulation during a period of one month. A comparative cellular uptake study was
modeled as a demonstration of active targeting using the HER2-positive (MCF-7/HER2+) and the HER2
negative (MDA-MB-231) breed cancer cell lines. The flow cytometry and confocal microscopy were performed
to observe low and non-specific uptake of the non-targeted PEGylated liposomes in both cell lines, which
demonstrates the property of stealthiness of the liposomes and the need to functionalize their surface. Finally, an
Irinotecan liposomal nanocarrier characterized and stable was established. These findings support the platform
as an emerging basis of future conjugation with any desired targeting ligand (e.g. anti-HER2 antibodies) to
undergo receptor-mediated active targeting, which is a key step to improving therapeutic efficacy and specificity
in oncology.