Stealth recombinant human serum albumin nanoparticles conjugating 5-fluorouracil augmented drug delivery and cytotoxicity in human colon cancer, HT-29 cells.

BACKGROUND AND OBJECTIVE

5-Fluorouracil (5-FU) is a first-line chemotherapeutic drug in colorectal cancer. However, intravenous administration of 5-FU at the dose of 7-12mg/kg exhibits curbs like short half-life (20min) and toxic side-effects on bone marrow cells. Therefore, in present investigation, 5-FU was conjugated to poly (ethylene glycol) anchored recombinant human serum albumin nanoparticles (5-FU-rHSA-PEG-NPs) to improve the pharmacokinetic and therapeutic profiles.

METHODS AND RESULTS

The mean particle size of 5-FU-rHSA-NPs was measured to be 44.3±5.8-nm, significantly (P<0.05) lesser than 65.7±7.2-nm of 5-FU-rHSA-PEG-NPs. In addition, zeta-potential of 5-FU-rHSA-NPs was estimated to be -10.2±2.6-mV significantly (P<0.05) lower than -25.8±3.5-mV of 5-FU-rHSA-PEG-NPs. Moreover, both 5-FU-rHSA-NPs and 5-FU-rHSA-PEG-NPs were smooth, spherical and regular in shape. In-vitro drug release analysis indicated that 5-FU-rHSA-NPs and 5-FU-rHSA-PEG-NPs separately released 10.9% and 9.23% of 5-FU in PBS (pH∼7.4) with no significant difference (P>0.05) up to 48h. However, addition of 20% v/v serum to PBS (pH∼7.4) boosted the drug release. 5-FU-rHSA-NPs and 5-FU-rHSA-PEG-NPs released 78.26% and 48.9% of the 5-FU up to 48h in presence of PBS (pH∼7.4 and 20% serum) with significant difference (P<0.05). Furthermore, 5-FU-rHSA-PEG-NPs displayed the IC of 3.7-μM significantly (P<0.05) lower than 6.8-μM and 11.2-μM of 5-FU-rHSA-NPs and 5-FU solution, respectively. One compartmental pharmacokinetic elements indicated that 5-FU-rHSA-PEG-NPs demonstrated the half-life (t) of 5.33±0.15-h significantly (P<0.001) higher than 1.50±0.08-h and 0.30±0.09-h of 5-FU-rHSA-NPs and 5-FU solution, respectively.

CONCLUSION

5-FU-rHSA-PEG-NPs tendered improved cytotoxicity and pharmacokinetic profile. Hence, 5-FU-rHSA-PEG-NPs must be further tested under stringent milieu for translating in to a clinical product.