Abstract
Novel peptide-conjugated doxorubicin-loaded PEGylated PLGA nanoparticles (CPDNPs) were developed for prolonged and effective delivery to prostate cancer (PCa) cells. Nanoparticles (NPs) were prepared using the nanoprecipitation method and optimized by applying a Box-Behnken design (BBD) using Design-Expert® Software where three independent and dependent variables were used. CPDNPs were characterized using FT-IR, NMR, Particle size analyser, SEM, and TEM. They were further studied for in vitro drug release, apoptosis, cellular uptake, hemolytic properties, and pharmacokinetics. The mean particle size, polydispersity index (PDI), and zeta potential (ZP) of CPDNPs were found to be 241.5 ± 2.23 nm, 0.291 ± 0.34 and −13.98 ± 4.36 mV, respectively. The entrapment efficiency, loading efficiency, and cumulative percentage drug release of doxorubicin (DOX) from CPDNPs were found to be 62.38 ± 1.76%, 2.8 ± 0.94%, and 73.26 ± 2.61%, respectively. Moreover, CPDNPs exhibited a greater (≥4-fold) cellular uptake and apoptosis (≥5-fold) against PC-3 cell lines and lesser hemolysis (9.40%). The pharmacokinetic study confirmed the improvement in AUC0-∞ (mcg h/mL) and T1/2 (h) of CPDNPs than DOX, DNPs, and PDNPs. It is concluded from the observations that among the prepared NPs, the CPDNPs could be employed as one of the potential nanocarriers for the targeting of PCa.
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