Coaxial double-walled microspheres for combined release of cytochrome c and doxorubicin

Feng, Fang; Neoh, Kar Yee; Davoodi, Pooya; Wang, Chi-Hwa

Abstract

Co-axial electrohydrodynamic atomization (CEHDA) can be adapted to fabricate core/shell microspheres with narrow size distribution in a single step for controlled and sustained release of therapeutic drugs [1]. Our previous studies evaluated the advantages of CEHDA for the encapsulation of BSA and hepatocyte growth factor, where it mitigated denaturation of bioactive compounds during fabrication process and subsequent release from biodegradable polymeric microparticles [2, 3]. In the present study (Fig. 1), we examined the versatile application of core/shell microspheres for co-encapsulating a therapeutic protein (cytochrome c, CC) and an anticancer drug (doxorubicin, DOX), which provide a synergistic chemotherapeutic effect upon co-delivery at target tissue. DOX, a FDA approved chemotherapeutic drug which can induce apoptosis in various cancer cells was used in combination with CC, which plays an important role in programmed cell death. The core-shell microparticles ranging from 1 to 9 μm were successfully fabricated using CEHDA technique. Two PLGA solutions (two different molecular weights with inherent viscosities of 0.26-0.54 dL/g and 0.65-0.85 dL/g, respectively) were used to study their effects on particle size and in vitro drug release. Additionally, the stability of CC was confirmed by ABTS assay and circular dichroism (CD). The CEHDA technique reduced the loss of potentially expensive solutes (94% encapsulation efficiency for CC), hence protecting the protein drug structure. Zero-order release of CC has been observed regardless of the formulations used. Combination of DOX and CC revealed a sequential release, where DOX was released at a higher dosage and higher rate than CC. Therefore, CC can act as a supplementary drug at the later stage to induce apoptosis. The synergistic effects of DOX and CC were evaluated in vitro via MTS cytotoxicity assay. Overall, the synergistic effect of protein/peptide and anticancer drugs released from core/shell microparticles can be proposed as a new treatment regimen to enhance treatment outcome.

Citation

Feng, F., Neoh, K. Y., Davoodi, P., & Wang, C. (2017). Coaxial double-walled microspheres for combined release of cytochrome c and doxorubicin. Journal of Controlled Release, 259, e30-e31. https://doi.org/10.1016/j.jconrel.2017.03.088

• Journal Article Type: Article
• Online Publication Date: Aug 1, 2017
• Publication Date: 2017-08
• Deposit Date: Jun 8, 2023
• Journal: Journal of Controlled Release
• Print ISSN: 0168-3659
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 259
• Pages: e30-e31
• DOI: https://doi.org/10.1016/j.jconrel.2017.03.088
• Keywords: Pharmaceutical Science