The main purpose of this study was to develop a prostate-specific membrane antigen (PSMA) antibody-conjugated drug-loaded nanomicelles using MPEG--PLA-PCL-PLA-PEG-NH2 pentablock copolymer for targeted delivery of hydrophobic anticancer drugs to prostate cancer cells. During this experiment, monomers of L-lactide, ε-caprolactone, poly(ethylene glycol)-methyl ether, and poly(ethylene glycol)-NH2 were used to prepare pentablock copolymer using the ring opening technique. The pentablock nanomicellar (PBNM) formulation was prepared by the evaporation-rehydration method. The resultant pentablock nanomicelles were then conjugated with PSMA antibody resulting in PSMA-Ab-PTX-PBNM. Both the block copolymers and the nanomicelles were analyzed by hydrogen nuclear magnetic resonance (H-NMR), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). The obtained nanomicelles (NM) were then analyzed for size and zeta potential using dynamic light scattering-dynamic laser scattering (DLS) and then further submitted to H-NMR and TEM analyses. The XRD, FTIR, and the H-NMR analyses confirmed the structure of the pentablock copolymers. The average size for conjugated nanomicellar was 45 nm ± 2.5 nm. The average (ζ-potential) was around - 28 mV. H-NMR and FTIR analysis done on PSMA-coupled paclitaxel-loaded PBNM showed peaks characteristic of the drug (paclitaxel) and the polymer, confirming the successful encapsulation. TEM analysis showed well-defined spherical morphology and confirmed the size range obtained by the DLS. In vitro release studies revealed sustained slow of PTX in phosphate buffer solution (PBS). Confocal scanning microscopy (TEM) of coumarin6-loaded in PBNM indicated that pentablock nanomicelles were internalized into the prostate cancer (PC-3) cells. Cell proliferation assay showed that nanomicelles ferried paclitaxel into the PC-3 cells and subsequently reduced the cell proliferation. The results depict PTX-PBNM-Ab as a suitable carrier for targeted delivery of drugs to prostate cancer cells.
Nanomicelles (NM) enhance solubility and absorption of active pharmaceutical ingredients (APIs). Various polymers and non-polymers are utilized to prepare nanomicellar formulations to achieve high absorption and delivery of drugs. The main purpose of this study was to develop drug-loaded nanomicelles with pentablock copolymers for paclitaxel delivery. Monomers of lactide, ε-caprolactone, and polyethylene-glycol were utilized to prepare pentablock copolymer by ring opening technique. The pentablock nanomicelles (PBNM) were formulated by evaporation and rehydration. Both copolymers and nanomicelles were analyzed by H-NMR, FTIR, and XRD. Nanomicelles were further analyzed for size and zeta potential using dynamic light scattering (DLS) and by H-NMR and TEM. The XRD, FTIR, and H-NMR analyses confirmed the structures of the pentablock copolymers. Average size was 20 nm ± 5.00 nm, and ζ-potential is around zero. H-NMR and FTIR analyses for Paclitaxel-PBNM indicated peaks of paclitaxel and the polymer, confirming successful encapsulation. TEM showed spherical morphology and size range similar to that obtained by DLS. In vitro release studies revealed slow first-order paclitaxel release rate from pentablock nanomicelles in phosphate buffer solution (PBS). Confocal laser scanning microscopy analysis with coumarin-6-loaded in PBNM indicated that pentablock nanomicelles were efficiently taken into prostate cancer (PC-3) cells. Cell proliferation assay showed that nanomicelles were able to ferry adequate amounts of paclitaxel drug into PC-3 cells and subsequently inhibiting PC-3 cell proliferation significantly. Results confirmed that pentablock copolymer can generate drug-loaded nanomicelles with desirable sizes and zeta potential. These demonstrate potentiality of pentablock nanomicelles as carrier for anticancer delivery.
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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