Gemcitabine cationic polymeric nanoparticles against ovarian cancer: formulation, characterization, and targeted drug delivery

Abstract

This study focused on gemcitabine (GTB) delivery of cationic polymeric nanoparticles to treat ovarian cancer in order to promote effective localized delivery and drug retention during biological discharge. To begin, four GTB-loaded polymer nanoparticles were prepared: chitosan nanoparticles (CS-NPs), polysarcosin nanoparticles (PSar-NPs), poly- l -lysine & polysarcosin nanoparticles (PLL-PSar-NPs), and chitosan & polysarcosin nanoparticles (CS-PSar-NPs). Based on preliminary particle size, zeta potential, encapsulation efficiency, DSC, surface morphology, release profiling, and cellular internalization studies using rhodamine 123 and Nile red fluorescent markers, it was hypothesized that CS-PSar-NPs could be the best cationic formulation with strong biocompatibility and anticancer activity against the OVCAR-8 ovarian cancer cell line. To improve effective targeting, cellular penetration, and in vitro cytotoxicity, epidermal growth factor receptor variation III (EGFRvIII) is attached over all four polymeric nanoparticles. Confocal imaging revealed that EGFRvIII-conjugated cationic GTB polymeric nanoparticles had a greater cellular uptake and double internalization capabilities than unconjugated nanoparticles, as well as time-dependent cell entrance. GTB and EGFRvIII-conjugated polymer nanoparticles would have a stronger potential to infiltrate ovarian cancer cells during the first hour of incubation. According to TEM and FTIR findings, EGFRvIII conjugation across the non-target CS-PSar-NP surface was successful, making CS-PSar-NPS-EGFRvIII more target-specific and thus a safer drug delivery candidate for ovarian cancer treatment. Highlights GTB loaded non-target CS-PSar-NPs & active targeted CS-PSar-NPs-EGFRvII developed. SEM, AFM, DSC, particle size, zeta potential, internalization performed for CS-PSar-NPs. MTT & CLSM study confirmed CS-PSar-NPS-EGFRvII was binding specific to OVCAR-8 cells Fabrication of EGFRvII over nanoparticles confirmed by TEM. CS-PSar-NPS-EGFRvII safer candidate for ovarian cancer.

Biocompatible Macroion/Growth Factor Assemblies for Medical Applications

“…The hydrogels activate macrophages for tumoricidal activity [ 174 ] and are applied in various stages of wound healing [ 160 ] and regenerative medicine [ 175 ]. On the other hand, CS-based nanoparticles were tested as safe carriers of drugs to treat ovarian cancer [ 176 ].…”

Antibacterial Triboelectric Nanogenerator for Mite Removal and Intelligent Human Monitoring

“…Surprisingly, the CHP film spectrum shows a narrow stretching peak of OH at 3676 cm −1 and a little bending vibration of NH at 1637 cm −1 which shows that chitosan is successfully linked with HEC/pectin polymer surface. [ 19 ] In addition, X‐ray diffraction patterns analysis results in Figure 2c show that all the prepared films have one distinct diffraction peak. The diffraction peak of HEC/pectin film and pure chitosan appear at 22° and 18° respectively.…”

Gemcitabine-Phospholipid Complex Loaded Lipid Nanoparticles for Improving Drug Loading, Stability, and Efficacy against Pancreatic Cancer

“…Similarly, Bhattacharya et al, evaluated the GEM loaded cationic polymeric nanoparticles and evaluated its physicochemical characteristics and activity against ovarian cancer cells. 11 The particles prepared using chitosan and polysarcosine followed by modification with EGFR variation III, showed promising results at the in vitro level, which can be evaluated further for its efficacy at the in vivo level as well. Furthermore, Paroha et al, has extensively compiled the advancements made in delivering GEM via several drug delivery systems.…”

“…Such a biomimicking coating led to reduced toxicity and assisted in improving the anticancer efficacy by increasing the accumulation in the tumor region. Similarly, Bhattacharya et al, evaluated the GEM loaded cationic polymeric nanoparticles and evaluated its physicochemical characteristics and activity against ovarian cancer cells . The particles prepared using chitosan and polysarcosine followed by modification with EGFR variation III, showed promising results at the in vitro level, which can be evaluated further for its efficacy at the in vivo level as well.…”