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RETRACTED: pH-Responsive Polymer Conjugate of Pirarubicin With Styrene Maleic Acid Copolymer as a Potential Therapeutic for Ovarian Cancer
- Source :
- Journal of Pharmaceutical Sciences. 105:1595-1602
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Previous studies indicated the potential of styrene maleic acid copolymer (SMA)econjugated pirarubicin (4 0-O-tetrahydropyranyldoxorubicin [THP]) for targeted anticancer therapy based on the enhanced permeability and retention effect. In this study, to achieve further improved therapeutic efficacy, a pH-responsive SMA-conjugated THP-containing hydrazone bond (SMA-hyd-THP) was synthesized and evaluated in vitro and ex vivo using human ovarian cancer cells and tissues. SMA-hyd-THP showed good water solubility, forming micelles with a mean particle size of 48.0 nm, which is applicable for enhanced permeability and retention-based tumor accumulation. The THP loading in this preparation was 15% (wt/wt), and release rate of free THP from SMA-hyd-THP at physiological pH (7.4) was approximately 10% in 72 h. However, it increased rapidly at pH 6.5 (42%) and 5.5 (83%), which indicates that tumor environment of weak acidic condition (pH 6.5-6.9) is favorable for release of THP. This notion was partly proved by incubating SMA-hyd-THP with tumor tissues from ovarian cancer patients. In addition, release of THP was not affected by serum, suggesting that SMA-hyd-THP is relatively stable in circulation. Finally, SMA-hyd-THP showed much increased cytotoxicity against various ovarian cancer cells at acidic tumor pH (6.5). These findings may provide an option for targeted therapy against ovarian cancer. © 2016 American Pharmacists Association
- Subjects :
- Maleic acid
medicine.medical_treatment
Pirarubicin
Pharmaceutical Science
hemic and immune systems
Enhanced permeability and retention effect
02 engineering and technology
Pharmacology
medicine.disease
021001 nanoscience & nanotechnology
Micelle
Targeted therapy
chemistry.chemical_compound
03 medical and health sciences
0302 clinical medicine
chemistry
030220 oncology & carcinogenesis
Polymer chemistry
medicine
lipids (amino acids, peptides, and proteins)
Cytotoxicity
Ovarian cancer
0210 nano-technology
Ex vivo
medicine.drug
Subjects
Details
- ISSN :
- 00223549
- Volume :
- 105
- Database :
- OpenAIRE
- Journal :
- Journal of Pharmaceutical Sciences
- Accession number :
- edsair.doi.dedup.....56270b15c39c4be445b3cff6c03b3197