Fabrication of Biodegradable Poly(d,l-lactide-co-glycolide) Nanoparticles Containing Tamoxifen Citrate

Biodegradable polymers have been extensively investigated as nano-carrierdelivery systems in anti-cancer therapy. The anti-cancer drugs generally sufferfrom low aqueous solubility, short in vivo half-life and haphazard side effects. Inthis work, biodegradable poly(d,l-lactide-co-glycolide) nanoparticles (PLGA) containingtamoxifen citrate as a model anti-cancer drug were prepared using an o/w emulsification-solvent evaporation method. Dynamic light scattering (DLS), scanning electronmicroscopy (SEM) and analytical HPLC procedures were used to characterize thenanoparticles in terms of particle size, morphology and drug content. The characteristicsof the nanoparticles including size, drug loading, and the efficiency ofencapsulation were optimized by means of a full factorial experimental design over theinfluence of four different independent variables. Analyses of variance (ANOVA) wereused to evaluate the optimized conditions for the preparation of nanoparticles. Basedon the results, the most significant variables were homogenization speed andconcentration of PLGA in organic phase with known total volume. Also, the interactionsbetween the percentage of PVA and the amount of PLGA and organic phase volumewere the most important cross-factor parameters. The optimum formulation conditionwith 192 nm mean size and 33 w/w% loading capacity was established by using3 mg.mL-1 PLGA/dichloromethane in 7 w/v% PVA solution and 40% oil/water solventratio for emulsification at 24000 rpm homogenization rate. The results of this workfacilitate the development of nano-carriers for tamoxifen delivery through optimizationstudies to control nanoparticles with specific properties and establish correlationsbetween optimum production conditions and the required nano-carrier desiredcharacteristics