Characterization of Long-Circulating Cationic Nanoparticle Formulations Consisting of a Two-Stage PEGylation Step for the Delivery of siRNA in a Breast Cancer Tumor Model

Ho, Emmanuel A.; Osooly, Maryam; Strutt, Dita; Masin, Dana; Hong, Yang; Bally, Marcel B.

doi:10.1002/jps.23351

Cited by 29 publications

(20 citation statements)

References 28 publications

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“…This could be due to the presence of PEG, placed on the outer surface of the lipid bilayer, causing an increase in drug entrapment within the bilayer [54][55][56]. More specifically, PEGylated liposomes with DOPC lipids showed a similar entrapment efficiency (75.6%) to previously prepared PEGylated formulations with DSPC, EPC and DPPC lipids (91.8%, 71.8%, and 84.9% respectively) [29].…”

Section: Entrapment Efficiencymentioning

confidence: 99%

Comparative Study of PEGylated and Conventional Liposomes as Carriers for Shikonin

Tsermentseli

Kontogiannopoulos

Papageorgiou

et al. 2018

Fluids

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Abstract:Liposomes are considered to be one of the most successful drug delivery systems.They apply nanotechnology to potentiate the therapeutic efficacy and reduce the toxicity of conventional medicines. Shikonin and alkannin, a pair of chiral natural naphthoquinone compounds, derived from Alkanna and Lithospermum species, are widely used due to their various pharmacological activities, mainly wound healing, antioxidant, anti-inflammatory and their recently established antitumor activity. The purpose of this study was to prepare conventional and PEGylated shikonin-loaded liposomal formulations and measure the effects of different lipids and polyethylene glycol (PEG) on parameters related to particle size distribution, the polydispersity index, the zeta potential, drug-loading efficiency and the stability of the prepared formulations. Three types of lipids were assessed (1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC) and 1,2-distearoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DSPG)), separately and in mixtures, forming anionic liposomes with good physicochemical characteristics, high entrapment efficiencies (varying from 56.5 to 89.4%), satisfactory in vitro release profiles and good physical stability. The addition of the negatively charged DSPG lipids to DOPC, led to an increment in the drug's incorporation efficiency and reduced the particle size distribution. Furthermore, the shikonin-loaded PEGylated sample with DOPC/DSPG, demonstrated the most satisfactory characteristics. These findings are considered promising and could be used for further design and improvement of such formulations.

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Section: Entrapment Efficiencymentioning

confidence: 99%

Comparative Study of PEGylated and Conventional Liposomes as Carriers for Shikonin

Tsermentseli

Kontogiannopoulos

Papageorgiou

et al. 2018

Fluids

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“…Grafting PEG chains onto the surface of siRNA/liposome complexes protects from reticuloendothelial system (RES) evasion and increases blood circulation time [39]. Due to the steric and electrostatic nature of PEG, the stealth liposomes delay the binding of opsonin proteins on its surface and the nanoparticles are able to circulate for long time, allowing them to accumulate in the tumor milieu in relatively high quantity.…”

Section: Liposomes and Lipid Nanoparticles For Sirna Deliverymentioning

confidence: 99%

Nanoparticles for siRNA-Based Gene Silencing in Tumor Therapy

Babu

Muralidharan

Amreddy

et al. 2016

IEEE Trans.on Nanobioscience

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Gene silencing through RNA interference (RNAi) has emerged as a potential strategy in manipulating cancer causing genes by complementary base-pairing mechanism. Small interfering RNA (siRNA) is an important RNAi tool that has found significant application in cancer therapy. However due to lack of stability, poor cellular uptake and high probability of loss-of-function due to degradation, siRNA therapeutic strategies seek safe and efficient delivery vehicles for in vivo applications. The current review discusses various nanoparticle systems currently used for siRNA delivery for cancer therapy, with emphasis on liposome based gene delivery systems. The discussion also includes various methods availed to improve nanoparticle based-siRNA delivery with target specificity and superior efficiency. Further this review describes challenges and perspectives on the development of safe and efficient nanoparticle based-siRNA-delivery systems for cancer therapy.

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“…Injection of PSLR resulted in significantly lower fluorescence intensities in tumor at 24 hours compared to mice that received EPSLR, revealing EPSLR affinity to MCF-7/ADR tumor. Compared to LR, the fluorescence intensity of PSLR or EPSLR in the tumor region was significantly increased at 24 hours postinjection, which was attributed to enhanced permeability and retention effect 58 or a combination effect with Eph-mediated endocytosis, 59 indicating that PEGylation is capable of prolonging circulation times of complexes in blood. Numerous reports showed that the nanoparticles with sizes ranging from 100 to 200 nm could take a longer circulation time than larger diameters.…”

Section: In Vivo Tumor-targeting Of Epslrmentioning

confidence: 99%

Anti-EphA10 antibody-conjugated pH-sensitive liposomes for specific intracellular delivery of siRNA

Zang¹,

Ding²,

Zhao³

et al. 2016

IJN

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Therapeutic delivery of small interfering RNA (siRNA) is a major challenge that limits its potential clinical application. Here, a pH-sensitive cholesterol–Schiff base–polyethylene glycol (Chol–SIB–PEG)-modified cationic liposome–siRNA complex, conjugated with the recombinant humanized anti-EphA10 antibody (Eph), was developed as an efficient nonviral siRNA delivery system. Chol–SIB–PEG was successfully synthesized and confirmed with FTIR and 1 H-NMR. An Eph–PEG–SIB–Chol-modified liposome–siRNA complex (EPSLR) was prepared and characterized by size, zeta potential, gel retardation, and encapsulation efficiency. Electrophoresis results showed that EPSLR was resistant to heparin replacement and protected siRNA from fetal bovine serum digestion. EPSLR exhibited only minor cytotoxicity in MCF-7/ADR cells. The results of flow cytometry and confocal laser scanning microscopy suggested that EPSLR enhanced siRNA transfection in MCF-7/ADR cells. Intracellular distribution experiment revealed that EPSLR could escape from the endo-lysosomal organelle and release siRNA into cytoplasm at 4 hours posttransfection. Western blot experiment demonstrated that EPSLR was able to significantly reduce the levels of MDR1 protein in MCF-7/ADR cells. The in vivo study of DIR-labeled complexes in mice bearing MCF-7/ADR tumor indicated that EPSLR could reach the tumor site rather than other organs more effectively. All these results demonstrate that EPSLR has much potential for effective siRNA delivery and may facilitate its therapeutic application.

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Characterization of Long-Circulating Cationic Nanoparticle Formulations Consisting of a Two-Stage PEGylation Step for the Delivery of siRNA in a Breast Cancer Tumor Model

Cited by 29 publications

References 28 publications

Comparative Study of PEGylated and Conventional Liposomes as Carriers for Shikonin

Comparative Study of PEGylated and Conventional Liposomes as Carriers for Shikonin

Nanoparticles for siRNA-Based Gene Silencing in Tumor Therapy

Anti-EphA10 antibody-conjugated pH-sensitive liposomes for specific intracellular delivery of siRNA

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