Preparation of Doxorubicin-Retinoic Acid Hip Complex Nanomicellar Formulation for Doxorubicin Delivery to Prostate Cancer by Alex Oselu Owiti in Journal of Urology & Nephrology Studies in lupinepublishers.
Doxorubicin is a hydrophilic anticancer drug. Due to hydrophilicity, it’s difficult to encapsulate in a hydrophobic core of nanomicelles. The main purpose of this study was to develop a hydrophobic ion paring complex (HIP) of doxorubicin using hydrophobic retinoic acid (Vitamin A). The resultant hydrophobic (DOX-RA) complex was utilized to prepare drug-loaded nanomicelles by co-precipitation method with penta block copolymer. Nanomicelles (DOX-RA/PBNM), was prepared by evaporation rehydration technique. DOX-RA complex was analyzed by H-NMR and FTIR. The nanomicelles were analyzed for size and zeta potential using dynamic light scattering (DLS) as well as transmission electron microscopy (TEM). The FT-IR and the H-NMR analyses confirmed the structures of the DOX-RA complex. Mean nanomicellar sizes were 25.5nm ± 5.00nm, and ΞΆ-potential was approximately zero. H-NMR and FTIR analysis done on DOX-RA indicate peaks characteristic of both doxorubicin and retinoic Acid. This confirmed successful complex formation. Transmission electron microscopy (TEM) analysis revealed round shaped morphology and sizes similar to DLS results. In vitro release studies revealed that pentablock nanomicelles released Doxorubicin at a slow first order rate in phosphate buffer solution (PBS) at pH 7.4 compared to pH 5.5 and pH 4.0. Confocal microscopy analysis with DOX-RA/ PBNM indicated that pentablock nanomicelles were efficiently taken into prostate cancer (PC3) cells and doxorubicin was efficiently released from the nanomicelles into the cells. In addition, cell proliferation assay showed that nanomicelles ferried adequate amounts of Doxorubicin into PC-3 cells and inhibited cell growth significantly. Results confirm that DOX-RA complex facilitated the encapsulation of doxorubicin within nanomicelles increasing DOX intracellular concentration.
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