Pegylated liquisomes: A novel combined passive targeting nanoplatform of L-carnosine for breast cancer.

Abstract PEGylated Liquisomes (P-Liquisomes), a novel drug delivery system was designed for the first time by incorporating phospholipid complex in PEGylated liquid crystalline nanoparticles (P-LCNPs). L-carnosine (CN), a challenging dipeptide, has proven to be a promising anti-cancer drug. However, it exhibits high water solubility and extensive in-vivo degradation that halts its use. The objective of this work was to investigate the ability of our novel system to improve the CN anticancer activity by prolonging it’s release and protecting it in-vivo. In-vitro appraisal revealed spherical light-colored vesicles encapsulated in the liquid crystals, confirming the successful formation of the combined system. P-Liquisomes were nano-sized (149.3 ± 1.4 nm), with high ZP (-40.2 ± 1.5 mV), complexation efficiency (97.5 ± 0.9 %) and outstanding sustained release of only 75.4 % released after 24 h, compared to P-LCNPs and Phytosomes. The results obtained with P-Liquisomes are considered as a break through compared to P-LCNPs or Phytosomes alone, especially when dealing with the hydrophilic CN. In-vitro cytotoxicity evaluation, revealed superior cytotoxic effect of P-Liquisomes (IC50 = 25.9) after 24 h incubation. Besides, P-Liquisomes proved to be non-toxic in-vivo and succeeded to show superior chemopreventive activity manifested by reduction of; % tumor growth (7.1%), VEGF levels (14.3 pg/g tissue), cyclin D1 levels 15.5 ng/g tissue and elevation in caspase-3 level (36.4 ng/g tissue), compared to Phytosomes and CN solution. Conclusively, P-Liquisomes succeded to achieve the maximum therapeutic outcome of CN without altering its activity and might be used as a sustained delivery system for other promising hydrophilic compounds.