Abstract
A Nano-in-Nano approach was exploited to facilitate incorporation of the chemotherapeutic drug etoposide (ETP) as nanosuspension, synergistically with berberine (BER) into hydrophilic albumin nanoparticles (HSA NPs). For maximal tumor targeting, HSA was modified with mannose and phenyl-boronic acid. Furthermore, different crosslinkers were investigated for sustained release of water soluble BER from HSA NPs. The elaborated dual-targeted HSA NPs (216.2nm) were spherical with high BER and ETP entrapment efficiency (69.5 and 87.6%, respectively) and loading (10.52 and 14.04%, respectively). The NPs exhibited sequential release pattern for both ETP and BER (51.55 and 34.33% over 72h, respectively). Phenyl-boronic acid/mannose-HSA NPs demonstrated powerful cytotoxicity against A549 lung cancer cells (IC50: 12.4μg/ml) correlated to enhanced cellular internalization. Dual-targeted NPs displayed 9.77-fold higher caspase-3 level and 3.5-fold lower VEGF level than positive control mice. Dual-targeted Nano-in-Nano albumin carriers could be beneficial for parenteral ETP/BER delivery to lung cancer.
Published Version
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