Journal
COLLOIDS AND SURFACES B-BIOINTERFACES
Volume 198, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.colsurfb.2020.111443
Keywords
Poly(epsilon-caprolactone); Redox responsive polymers; Amphiphilic block copolymers; Micelles; Drug delivery system
Funding
- Ministry of Science and Technology of Taiwan [MOST109-2320-B-037-017-MY3, MOST108-2221-B-037-002-MY3]
- Kaohsiung Medical University [KMU-DK109001]
- NSYSU-KMU Joint Research Project
- NSYSUKMU [109-P009]
- Center for Research Resources and Development of Kaohsiung Medical University
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The study developed a pH/redox-responsive polymer micelle for dual drug delivery, showing that co-loading cisplatin and paclitaxel into the micelle had a synergistic effect in killing lung cancer cells, demonstrating superior antitumor activity compared to single drugs or equivalent drug combinations.
Combining dual drugs in one vehicle to cancer cells offers spatiotemporal localization of drug at the site of action, leading to synergistic therapeutic effects and reduced side effects. To improve pH/redox responsiveness to the tumor microenvimnments for cancer therapy, a pH/redox-responsive micelle based on poly(epsilon-caprolactone)-SS-poly(methacrylic acid) (PCL-SS-PMAA) diblock copolymer was fabricated for dual drug delivery. The PCL-SS-PMAA was formulated into a core-shell micelle (PSPm) in an aqueous solution. The critical micelle concentration (CMC) values of PSPm were 7.94 x 10(-3) mg mL(-1) at pH 5.0 and 1.00 x 10(-2) mg mL(-1) at pH 7.4. The hydrodynamic diameters of PSPm were within 210-270 nm, depending on pH values. Changes in morphology and size of PSPm were clearly observed before and after exposure to a reducing agent. Paclitaxel (PTX) was encapsulated into the core and cisplatin (CDDP) was chelated on the shell of PSPm, with both PTX and CDDP being efficiently released from PSPm in the presence of a reducing agent in an acid condition. MTT and annexin V/propidium iodide dual staining results demonstrated that co-loading of CDDP and PTX into PSPm had a synergistic effect in killing lung cancer cells and exerted superior antitumor activity over the combination of single drug-loaded PSPm or the combination of free-CDDP and free-PTX at equivalent drug amounts. Hence, encapsulating the dual drugs into PSPm exhibits a synergistic effect for potential lung cancer therapy.
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