Folate Targeted Polyacrylamide/Punicic acid Nanomicelles for Flutamide Delivery in Prostate Cancer: Characterization, In Vitro Biological Evaluation and its DFT study.

BACKGROUND: Targeted nanocarriers can be used for reducing the un-wanted side effects of drugs in non-target organs. Punicic acid the polyunsaturated fatty acid of pomegranate seed oil has been shown to possess anti-cancer effects on prostate cancer. The objective of the current study was to synthesize a co-polymeric micelle for delivery of flutamide (FL) in prostate cancer using Polyacrylamide (PAM) and Punicic acid (PA). METHODS: The copolymer of PAM and PA was synthesized and conjugated to folic acid. The successful conjugation was studied computationally by the density functional theory method and confirmed by FT-IR and 1HNMR. The folate-PAMPA micelles produced by film casting method were characterized physically. FL was loaded in the nanomicelles and its release test was done at different pH. The critical micelle concentration (CMC) was measured by pyrene as a fluorescent probe. Their cellular uptake and cytotoxicity were evaluated on PC3 prostate cancer cells. The molecular geometry and vibrational frequencies of two different possibilities for conjugation were calculated using the B3LYP/6-31G basis set. RESULTS: The CMC of the micelles and their particle size were 79.05 μg/ml and 88 nm, respectively. The resulting nanocarriers of FL showed significant more cytotoxic effects than the free drug at a concentration of 25 μM. The calculated results showed the optimized geometries could well reproduce the structural parameters, and the theoretical vibrational frequencies were in good agreement with the experimental values. CONCLUSION: folate-PAMPA nanomicelles may be promising for enhancement of FL cytotoxicity and seem to potentiate the effect of chemotherapeutic agents used in prostate cancer treatment.