Speaker
Description
"Introduction. Breast cancer is considered nowadays the most common cause of death for female population. Since traditional treatments (e.g., chemotherapy, radiotherapy, surgery) showed several drawbacks [1], Drug Delivery Systems (DDS) recently gained interest due to the possibility to release therapeutic agents locally and controllably in targeted sites. Herein, we aimed to develop stable drug-loaded alginate microspheres (MS) encapsulating a natural anti-tumoral drug, curcumin, to be released in the tumor site [2]. Unloaded and drug-loaded MS were investigated by a morphological, chemo-physical, and biological characterization.
Materials and Methods. Sodium alginate (3% w/V) was dissolved in distilled water and alginate MS were obtained by extrusion dripping, using a coaxial needle (dint = 26G, dext = 20G), connected to a compressor which allowed a laminar air flow (P = 0.5 bar). Alginate droplets were chemically crosslinked in a CaCl2 (450, 900 mM) bath, and MS were then collected. In vitro stability tests were carried out on curcumin-loaded (0.3% w/V) and unloaded MS formulations, in neutral (pH = 7.4) and acidic (pH = 5.3) environment. Then, curcumin-loaded alginate MS were investigated in terms of encapsulation efficiency (EE%) and drug release. Lastly, in vitro biological tests were performed to investigate the effect of curcumin-loaded alginate MS on MCF-7 tumoral cells, previously 2D-seeded.
Results and Discussion. Extrusion parameters were selected through MS morphological analysis (threshold: Ø < 1.5 mm, circularity > 0.6) [3] [4]: A3-C450-0.5, A3-C900-0.5. In vitro tests stability exhibited no significant differences (p > 0.05) between alginate MS formulations in the same environment. This finding suggested that alginate MS reached the maximum swelling when crosslinked in 450 mM CaCl2. Differences (p < 0.05) were noticed comparing swelling kinetic in the two environments: degradation rate appeared faster (130 h) at pH 7.4 than at pH 5.3 (1008 h). EE% resulted higher (p < 0.05) for A3-C450-0.5-Cur than for A3-C900-0.5-Cur. As regards, alginate instantaneous crosslinking allowed for a higher drug release from MS, diminishing EE% [5]. Furthermore, drug release tests did not show significant differences (p > 0.05) between two CaCl2 concentration. Otherwise, the environment allowed for a lower drug release in acidic environment for both the formulations. In vitro biological tests showed that MCF-7 tumoral cells exhibited an increasing metabolic activity when cultured in contact with drug-unloaded alginate MS, as expected. Cell metabolism decreased when MCF-7 cells were cultured in presence of curcumin-loaded alginate MS.
Conclusions. Optimized alginate MS were tested as DDS in our work to develop a stable and controllable anti-tumoral therapy for breast cancer treatment. As regards, in vitro biological tests showed DDS efficiency in terms of drug release, which resulted time prolonged and specific. As regards, MCF-7 tumoral cells cultured on TCPS decreased their cell metabolism once in presence with curcumin-loaded MS.
1 American Cancer Society, American Cancer Society (2019)
2 Sookkasem, A. et al., RSC Advances, 8753-8756 (2015)
3 Lee, B. B. et al., Chemical Engineering and Technology, 1627-1642 (2013)
4 Lin, S. F. et al., PLOS ONE (2016)
5 Rastogi, R. et al., International Journal of Pharmaceutics, 71-77 (2007)"
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