Abstract:
Berberine (BBR), an isoquinoline alkaloid naturally derived from Berberis vulgaris and many other plant families, constitutes various pharmacological effects including anticancer properties. Particularly in breast carcinoma, berberine has been reported to target multiple pathways ranging from cell cycle arrest to the suppression of angiogenesis to mitochondria-directed apoptosis. However, low bioavailability,hydrophobicity, and low plasma concentration render the compound poor pharmacokinetics which limits its current use to dietary supplements, consumed with other nutritional products. In this study, a
biocompatible liquid crystalline colloidal system consisting of monoolein and Poloxamer 407was explored for improved delivery to cultured tumour cells via the enhanced permeation and retention (EPR) effect. BBR-LCN-THP, a formulation containing Transcutol® HP (THP), was negatively charged at -9.29 ± 0.68 mV, recorded mean particle size of 188.77 ± 0.80 nm, PDI 0.16 ± 0.01, and had demonstrated highest entrapment efficiency (88.14 ± 0.29%), and prolonged release (plateau ~80%) across 24 hours. Good colloidal stability was maintained
during storage at 25°C and 37°C for about 10 days before degradation was detected. The IC50
of BBR-LCN was about 10-fold lower compared to plain berberine, while the IC50 of BBRLCN-
THP and BBR-LCN-PEG were about 55-times significantly lower than free berberine.
Enhanced in vitro cytotoxicity, enhanced cellular uptake in MCF7 human breast cancer cells
as well as in Caco-2 human colonic cell line, and cell cycle arrest at G1/G0 phase to attenuate cell cycle progression were attractive advantages demonstrated by the fabricated liquid crystalline dispersion systems. Therefore, this study has unravelled the unique tunable characteristics of three formulated LCN carriers of berberine and the optimized LCNs may be potentially developed for oral administration, presenting opportunities as systemic treatment for heterogeneous and/or drug-resistant oestrogen-positive breast carcinoma. Further studies are required to validate nonlinear dose-response relationships and underlying molecular
mechanisms of cellular interactions.
Keywords: Berberine, liquid crystalline nanoparticles, colloid, monoolein, PEG, MCF7, Caco-2, anticancer, entrapment efficiency, drug release, cellular uptake, internalization
