Tuesday, May 13, 2014

PolyVivo AK02 used for Ovarian Cancer drug delivery

PolySciTech (www.polyscitech.com) provides mPEG-PLGA 2000-4110 (PolyVivo AK02). Recently this polymer was utilized as part of a nanostructured system to deliver all-trans retinoic acid to ovarian cancer cells.  Read more: Narvekar, Mayuri, Hui Yi Xue, Ngoc T. Tranx, Mariam Mikhael, and Ho Lun Wong. "A new nanostructured carrier design including oil to enhance the pharmaceutical properties of retinoid therapy and its therapeutic effects on chemo-resistant ovarian cancer." European Journal of Pharmaceutics and Biopharmaceutics (2014). http://www.sciencedirect.com/science/article/pii/S0939641114001313
Polymer-oil nanostructured carrier (PONC) designed for ATRA delivery.
PONC shows higher encapsulation efficiency and controlled release of ATRA.
Inclusion of oil in PONC enhances polymer amorphosity and drug dispersion.
ATRA-PONC more effective against ovarian cancer cell resistant to 300 nM paclitaxel.
Mechanistic studies indicated higher drug permeation into chemoresistant cancer cells.

Abstract: All-trans retinoic acid (ATRA) is an appealing alternative drug for the cancers that have failed the conventional chemotherapy and become chemo-resistant and more tumorigenic. In this study, we specifically addressed two issues commonly associated with ATRA nanotherapeutics: (1) insufficient, unstable entrapment and uncontrolled release of the highly lipophilic ATRA and (2) lack of studies in therapeutically relevant chemo-resistant cancer cell models. A polymer-oil nanostructured carrier (PONC) composed of oil and PLGA was designed and studied in an ovarian cancer cell subline SKOV-3PR that could withstand up to 300 nM paclitaxel and expressed high levels of multidrug resistance transporter ABCB1 and tumorigenic marker CD133. Differential scanning calorimetry of PONC revealed superior polymer amorphosity and dispersion of the entrapped ATRA in a manner comparable to nanostructured lipid carriers. With this design, the ATRA encapsulation efficiency was increased up to 8.5-fold and a 5-day controlled release profile was obtained. ATRA-PONC was able to induce extensive apoptotic cell death and exert substantially higher long-term anti-tumorigenic effects (IC50 of ATRA-PONC: 2 μg/ml versus free ATRA: 17.5 μg/ml; p < 0.05) in SKOV-3PR cells. Mechanistic studies indicated that these enhanced anticancer effects were likely attributable to higher cell permeation by the well-dispersed drug/oil steadily released from PONC. To conclude, a nanostructured, oil-in-polymer hybrid carrier design has been developed for efficient ATRA delivery and treatment of the chemo-exposed, chemo-resistant sub-population of ovarian cancer, exemplifying a convenient strategy to vastly improve the pharmaceutical and therapeutic properties of tough-to-deliver lipophilic, poorly water-soluble anticancer compounds. Abbreviations:

ABC, ATP-binding cassette; ATRA, all-trans-retinoic acid; BSA, bovine serum albumin; DSC, differential scanning calorimetry; EE, encapsulation efficiency; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PBS, phosphate buffered saline; PEG, polyethylene glycol; PLGA, poly(lactic-co-glycolic) acid; PLGA-np, poly(lactic-co-glycolic) acid nanoparticles; PONC, polymer-oil nanostructured carriers; PVA, polyvinyl alcohol; TEM, transmission electron microscope. Keywords: Controlled drug delivery; Nanomedicine; All-trans-retinoic acid; Poorly-water soluble drugs; Chemoresistance; Ovarian cancer”

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