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

被引:40
作者
Bhattacharya, Sankha [1 ]
Anjum, Md Meraj [2 ]
Patel, Krishna Kumar [2 ]
机构
[1] SVKMS NMIMS Deemed Univ, Sch Pharm & Technol Management, Dept Pharmaceut, Shirpur 425405, Maharashtra, India
[2] Banaras Hindu Univ, Dept Pharmaceut Engn & Technol, Indian Inst Technol, Varanasi, Uttar Pradesh, India
关键词
Gemcitabine; polysarcosin; OVCAR-8; EGFR vIII; confocal microscopy; CHITOSAN; SYSTEM;
D O I
10.1080/10717544.2022.2058645
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:1060 / 1074
页数:15
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