DHP107, a novel oral paclitaxel formulation induces less peripheral neuropathic pain and pain-related molecular alteration than intravenous paclitaxel preparation in rat

Paclitaxel is used in the treatment of cancer especially in breast, stomach and ovarian cancer. However, peripheral neuropathic pain (PNP) induction is the most common devastating side effect of paclitaxel treatment. The objective of this study was to evaluate the PNP related behavioral changes in rats following oral administration of a novel oral paclitaxel formulation DHP107 (Liporaxel) in comparison with another popular intravenous paclitaxel preparation (Taxol). The rats were equally divided in to three groups namely, NC group (normal control): was treated with saline in a matched volume, LPX group (Liporaxel were administered orally) and TAX group (Taxol was administered intravenously). Less pain like behaviors were observed in LPX group in comparison with TAX group evidenced by significant higher level of hot plate paw withdrawal threshold (PWT), von Frey filament PWT and mechanical PWT than TAX group. Reduced lipid peroxidation and elevated antioxidant activities in serum, dorsal root ganglion (DRG) and sciatic nerve (SN) in LPX group than TAX group. In addition, cell apoptosis and expression of pain and neuropathy related proteins activation in LPX group was found lowered and myelin sheath thickness was higher in DRG and SN but not significantly different from the TAX group. Therefore, oral DHP107 could be a promising chemotherapeutic agent due to inducing less PNP.