Preparation of Doxorubicin-Retinoic Acid Hip Complex Nanomicellar Formulation for Doxorubicin Delivery to Prostate Cancer
Volume 1 - Issue 4
Alex Oselu Owiti1*, Dhananjay Pal2 and Ashim Mitra2
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- Department of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, USA
- Department of Pharmaceutical sciences, University of Missouri Kansas City.
*Corresponding author:
Alex Oselu Owiti PhD, Department of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-
Kansas City, USA
Received: February 26, 2019; Published: March 07, 2019
DOI: 10.32474/JUNS.2019.01.000118
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Abstract
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 ζ-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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