Effect of fiber length of carbon nanotubes on the absorption of erythropoietin from rat small intestine

Erythropoietin (EPO) loaded carbon nanotubes (CNTs) with surfactant as an absorption enhancer were prepared for the oral delivery of EPO using two types of CNTs, long and short fiber length CNTs, and the effect of CNT fiber length on the absorption efficiency of EPO was studied. After Labrasol, PEG-8 caprylic/capric glycerides, as absorption enhancer was adsorbed into long fiber CNTs of which mean fiber length was 20–80 μm, as a carrier, EPO and casein as protease inhibitor and Explotab (sodium starch glycolate) as a disintegrating agent, were mixed. The resulting solid preparation was administered into the rat jejunum and serum EPO levels were measured by ELISA. The dose of EPO, CNTs, casein and Explotab were 100 IU/kg, 5 mg/kg, 25 mg/kg and 2.5 mg/kg, respectively. Serum EPO level reached to Cmax, 69.0 ± 3.9 mIU/ml, at 3.5 ± 0.1 h and AUC was 175.7 ± 13.8 mIU h/ml. These values were approximately half of that obtained with short fiber length CNTs of which Cmax was 143.1 ± 15.2 mIU/ml and AUC was 256.3 ± 9.7 mIU h/ml. When amphoteric surfactant, Lipomin LA, sodium β-alkylaminopropionic acid, was used to accelerate the disaggregation of long fiber length CNTs, Cmax was 36.0 ± 4.9 and AUC was 96.9 ± 11.9, which showed less bioavailability (BA) of EPO. These results suggest that the short fiber length CNTs deliver more both EPO and absorption enhancer to the absorptive cells of the rat small intestine and the aggregation of CNTs is not the critical factor for the oral delivery of EPO.