The effects of process variables on physicochemical properties and in-vitro cytotoxic activities of -fluorouracil squamous cell carcinoma (SCC)

Background: A 23 factorial experimental design was used to study the effects of polymer type, Neem and Acacia (A), the nature of the organic phase (B) and the homogenization speed (C) on the particle sizes (S), the amount of drug entrapped (E) and the in-vitro release properties of the formulations ®.

Objective: This study was aimed at quantifying the effects of three production variables on the physicochemical and cytotoxic activities of 5-Fluorouracil nanoparticles.

Methods: 5-Fluorouracil polymeric nanoparticles (TD1-8) were prepared using emulsion evaporation technique. The particle sizes were estimated using the dynamic light scattering technique, in-vitro drug release studies were conducted using membrane dialysis bag, while the amount of drug entrapped was spectrophotometrically determined. The in-vitro cytotoxic activities of the formulations were estimated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay.

Results: The effects of A, B, C, AC, BC, and ABC on S, E and R were expressed as coefficients of the polynomial equations generated. The effects of A, B and C on E were positively correlated, but that of A and B on R and S were inversely proportional. The ranking for combined effects on the R was, AC ≤BC≤ABC, while that of E and S were, BC≤ABC≤AC and ABC≤BC≤AC respectively. All formulations show significantly different cytotoxic action against HSC-1 cells. Cell mortality of TD3, 6, 7and 8 were above 80% while that of TD1, 2, 4 and 5 range between 62.2-65.6 %. Interestingly 5FU polymeric nanoparticles with low particle sizes released higher percentage of the entrapped drug with corresponding higher cell mortality.

Conclusion: The two natural biodegradable polymers (Neem and Acacia) investigated were successfully used to synthesize 5 FU polymeric nanoparticles. The production parameters investigated in this study had significant effects on the physicochemical and cytotoxic properties of 5FU nanoparticles.