Background: Berberine (BBR) broadly found in medicinal plants has a major application in pharmacological therapy as an anticancer drug. Clinical applications of this promising natural drug are limited due to its poor water solubility and low bioavailability.
Objective: In this study, for the first time, we synthesized core-shell BBR-loaded PLA nanoparticles (NPBs) by using coaxial electrospray (CES) to solve the poor bioavailability of BBR.
Methods: Three-factor (feeding rate, polymeric solution concentration and applied voltage), three-level, Box-Behnken design was used for optimization of the size and particle size distribution of the prepared NPBs.
Results: Based on the results of response surface methodology, the NPBs with the mean size of 265 nm and particle size distribution of 43 nm were synthesized. A TEM image was used to well illustrate the core-shell structure of the NPBs. Encapsulation efficiency and BBR loading capacity for the optimized NPBs were determined at about 81% and 7.5%, respectively. Release of NPBs was examined at pH 7.4 and 5.8. NPBs had a slower release profile than free BBR in both pH values, and the rate of BBR release was more and faster in acidic pH than in physiological one. Effects of the NPBs on the drug release were confirmed by data fitting with six kinetic models. NPBs showed an increased cytotoxic efficacy against HCT116 cells (IC = 56 μM), while NIH3T3 cells, non-neoplastic fibroblast cells, (IC > 150 μM) were less affected by NPBs. Flow cytometry demonstrated that the cellular uptake of NPBs were higher than BBR at different concentrations.
Conclusions: A new approach was developed in this study to prepare NPBs using the CES process for improving the efficiency and controlled BBR release. It is concluded that nano-scaled NPBs prepared by CES can improve toxicity and chemotherapeutic properties of BBR against cancerous cells. We believe that these NPBs can exhibit further potential in cancer drug delivery systems. Graphical abstract.
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| http://dx.doi.org/10.1007/s40199-020-00335-y | DOI Listing |
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