Magnetic Lipid-Based hybrid nanosystems: A combined stimuli- responsive nanocarriers for enriched chemotherapeutic potential of L-carnosine in induced breast Ehrlich ascites tumor model

Passent M. E. Gaafar,Ragwa M. Farid, Heba A. Hazzah, HussamElDin Y. AbouKilila, Maged W. Helmy,Ossama Y. Abdallah

INTERNATIONAL JOURNAL OF PHARMACEUTICS(2024)

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摘要
Magnetic Lipid-Based Hybrid Nanosystems (M-LC NPs ) is a novel nanoplatform that can respond to magnetic stimulus and are designed for delivering L-carnosine (CN), a challenging dipeptide employed in the treatment of breast cancer. CN exhibits considerable water solubility and undergoes in -vivo degradation, hence restricting its application. Consequently, it is anticipated that the developed M-LC NPs will enhance the effectiveness of CN. To ensure the physical stability of MNPs, they were initially coated with a mixture of oleic acid and oleylamine before being included in pegylated liquid crystalline nanoparticles ( P LCNPs). The proposed M-LC NPs exhibited promising in -vitro characteristics, notably a small particle size (143.5 nm +/- 1.25) and a high zeta potential (-39.5 mV +/- 1.54), together with superparamagnetic behavior. The in -vitro release profile exhibited a prolonged release pattern. The IC 50 values of M-LC NPs were 1.57 and 1.59 times lower than these of the CN solution after 24 and 48 hours, respectively. Female BALB/C female mice with an induced breast cancer (Ehrlich Ascites tumor [EAT] model) were used to study the influence of an external magnetic field on the chemotherapeutic activity and toxicity of CN loaded in the developed M-LC NPs . Stimuli-responsive M-LCNPs exhibited no apparent systemic toxicity in addition to enhanced chemotherapeutic efficacy compared to nontargeted M-LC NPs and CN solution, as evidenced by a reduction of % tumor growth (11.7%), VEGF levels (22.95 pg/g tissue), and cyclin D1 levels (27.61 ng/g tissue), and an increase in caspase-3 level (28.9 ng/g tissue). Ultimately, the developed stimuli-responsive CN loaded M-LC NPs presented a promising nanoplatform for breast cancer therapy.
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关键词
Magnetic lipid-based hybrid nanosystems,Stimuli-responsive,Dipeptide L-carnosine,Breast cancer
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