Nonviral gene carriers composed of biodegradable polymers or lipids have been considered as a safer alternative for gene carriers over viral vectors. We have developed multifunctional nanomicelles for both drug and gene delivery application. Polyethylenimine (PEI) was modified by grafting stearic acid (SA) and further formulated to polymeric micelles (PEI-SA) with positive surface charge for gene delivery evaluation. Our results showed that PEI-SA micelles provided high siRNA binding efficiency and exhibited low cytotoxicity compared with unmodified PEI. siRNA delivered by PEI-SA carriers also demonstrated significantly higher cellular uptake efficiency and stability even in the presence of serum proteins when compared with free siRNA. The post-transcriptional gene silencing efficiency was greatly improved by the polyplex formulated by 10k PEI-SA/siRNA. In the animal intratumoral model study, the combination of co-delivering doxorubicin and vascular endothelial growth factor (VEGF) siRNA delivered by PEI-SA micelles showed a promising effect on anti-tumor growth. The amphiphilic structure of PEI-SA micelles provides advantages for multifunctional tasks; such that hydrophilic shell modified with cationic charges can electrostatically interact with DNA or siRNA, and hydrophobic core can serve as a payload for hydrophobic drugs, making it truly a promising multifunctional vehicle for both genetic and chemotherapy application.
A novel carrier on balancing the transfection efficiency and minimizing cytotoxicity was designed. Gelatin cross-linked with 1.8 kDa of PEI (GA-PEI 1.8 k) formed stable complex and resulted in high positiveζpotential (42.47 mV) and buffering effect. These nanoparticles with N/P ratio of 30 give high transfection efficiency RLU/μg protein and cell viability (86.4%). These modified GA-PEI nanoparticles, with high transfection efficiency and low cell toxicity, can be a potential gene vector in gene therapy.
Gene delivery remains to be a very challenging field to efficiently transport the therapeutic gene and to modulate proteins with the desired function at the target site. The physiochemical and biological barriers are the major hurdles that need to be considered, particularly when administered systematically, in order to optimize the therapeutic efficacy. Numerous modifications have been extensively investigated aiming to provide protection from the plasma degradation, enhancement of transfection, target specificity, and most importantly, minimizing the side effects such as cellular toxicity and immune response. This article provides a review with respect to the in vitro and in vivo toxicity, as well as cellular and physiological interactions with the gene delivery system composed from viral vectors, cationic lipids and polymers. Recent progress and development are also addressed, with promising results that may be further adopted for clinical use.
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